• The experimental determination of C lambda using an absorbed dose calorimeter.

      Williams, Peter C; Regional Dept. of Medical Phys. & Bioengng., Christie Hospital, Manchester, UK (1980-01)
      The absorbed dose conversion factors, C lambda, were introduced, by Greene and Massey, as an interim measure until a primary standard for high energy photon dosimetry could be established. The theoretical basis of these factors has been discussed extensively and a more rigorous definition has emerged. Experiments have been carried out to determine the values of C lambda, for a Tufnol walled, Baldwin-Farmer ionisation chamber over a range of energies from cobalt-60 to 12 MV. The experimental results, based on measurements with a calorimeter, presented here support the more rigorous definition but it is shown that the values obtained depend, to a small extent, on the assumptions made about the detailed construction of the ionisation chamber for which C lambda is measured.
    • An experimental investigation of the tongue and groove effect for the Philips multileaf collimator.

      Sykes, Jonathan R; Williams, Peter C; North Western Medical Physics Department, Christie Hospital NHS Trust, Manchester, UK. prsjrs@dalpha2.cr.man.uk (1998-10)
      The tongue and groove effect is an underdosing effect which can occur in certain applications of multileaf collimators. It results from the need to overlap adjacent leaves of a multileaf collimator in order to limit leakage between leaves. The applications in which the effect can occur are the abutment of fields where the beam edges are defined by the leaf edge and the production of intensity-modulated fields by dynamic collimation. The effect has been measured for the 'worst case' when just two MLC fields are matched along leaf edges which have overlapping steps. Measurements of the dose have been made at d(max) and also at a more clinically relevant depth of 87 mm in Perspex for beam energies of 6 MV, 8 MV and 20 MV on two Philips SL series accelerators. Dose distributions were recorded on radiographic film which was subsequently digitized for analysis. The dose reduction of the tongue and groove effect was found to be 15-28% and spread over a width of 3.8 to 4.2 mm. This is somewhat shallower and wider than would be expected from a simple, idealized model of the effect which would predict a dose reduction of 80% over a width of 1 mm.
    • Experimental validation of estimated spatially variant radioisotope-specific point spread functions using published positron range simulations and fluorine-18 measurements.

      Anton-Rodriguez, Jose M; Krokos, G; Kotasidis, F; Asselin, M; Morris, O; Julyan, Peter J; Archer, A; Matthews, J; Division of Informatics, Imaging and Data Sciences, MAHSC, University of Manchester, Manchester, United Kingdom (2018)
      In this work we compare spatially variant radioisotope-specific point spread functions (PSFs) derived from published positron range data with measured data using a high resolution research tomograph (HRRT). Spatially variant PSFs were measured on a HRRT for fluorine-18, carbon-11 and gallium-68 using an array of printed point sources. For gallium-68, this required modification of the original design to handle its longer positron range. Using the fluorine-18 measurements and previously published data from Monte-Carlo simulations of positron range, estimated PSFs for carbon-11 and gallium-68 were calculated and compared with experimental data. A double 3D Gaussian function was fitted to the estimated and measured data and used to model the spatially varying PSFs over the scanner field of view (FOV). Differences between the measured and estimated PSFs were quantified using the full-width-at-half-maximum (FWHM) and full-width-at-tenth-maximum (FWTM) in the tangential, radial and axial directions. While estimated PSFs were generally in agreement with the measured PSFs over the entire FOV better agreement was observed (FWHM and FWTM differences of less than 10%) when using one of the two sets of positron range simulations, especially for gallium-68 and for the FWTM. Spatially variant radioisotope specific PSFs can be accurately estimated from fluorine-18 measurements and published positron range data. We have experimentally validated this approach for carbon-11 and gallium-68, and such an approach may be applicable to other radioisotopes such as oxygen-15 for which measurements are not practical.
    • Experimental verification the Electron Return Effect around spherical air cavities for the MR Linac using Monte Carlo calculation

      Shortall, J; Vasquez Osorio, Eliana; Aitkenhead, Adam H; Berresford, Joe; Agnew, James Paul; Budgell, Geoff J; Chuter, Robert; McWilliam, Alan; Kirkby, Karen J; Mackay, Ranald I; et al. (2020)
      PURPOSE: Dose deposition around unplanned air cavities during MR Guided Radiotherapy (MRgRT) is influenced by the Electron Return Effect (ERE). This is clinically relevant for gas forming close to or inside Organs At Risk (OAR) that lie in the path of a single beam, e.g. intestinal track during pelvic treatment. This work aims to verify Monte Carlo calculations that predict the dosimetric effects of ERE around air cavities. For this we use GafChromic EBT3 film inside poly-methyl methacrylate (PMMA) -air- PMMA phantoms. METHOD: Four PMMA phantoms were produced. Three of the phantoms contained centrally located spherical air cavities (0.5, 3.5, 7.5 cm diameter), and one phantom contained no air. The phantoms were split to sandwich GafChromic EBT3 film in the centre. The phantoms were irradiated on an Elekta Unity system using a single 10x10 cm2 7 MV photon beam under the influence of a 1.5 T transverse magnetic field. The measurements were replicated using the Elekta Monaco Treatment Planning System (TPS). Gamma analysis with pass criteria 3%/3mm was used to compare the measured and calculated dose distributions. We also consider 3%/2mm, 2%/3mm and 2%/2mm pass criteria for interest. RESULTS: The gamma analysis showed that >95 % of the points agreed between the TPS calculated and measured dose distributions, using 3%/3mm criteria. The phantom containing the largest air cavity had the lowest agreement, with most of the disagreeing points lying inside the air cavity (dose to air region). CONCLUSION: The dose effects due to ERE around spherical air cavities are being calculated in the TPS with sufficient accuracy for clinical use.
    • Expert consensus for the management of advanced or metastatic pancreatic neuroendocrine and carcinoid tumors.

      Castellano, D; Grande, E; Valle, Juan W; Capdevila, J; Reidy-Lagunes, D; O'Connor, J; Raymond, E; Departamento de Oncología Médica, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041, Madrid, Spain (2015-06)
      Neuroendocrine tumors (NETs) are rare tumors that have been increasing in incidence over the last 30 years with no significant changes in survival. As survival of patients with these tumors depends greatly on stage and histology, early diagnosis, classification and staging of tumors in patients in whom NETs are suspected are of great importance. Surgery, either with curative or palliative intent, is the mainstay of treatment for localized NETs. Therapeutic options for this disease almost invariably include somatostatin analogs to alleviate the symptoms of excessive hormone secretion. Other approaches for advanced disease may include hepatic artery embolization or ablation, peptide receptor radionuclide therapy and systemic chemotherapy. Recent advances regarding the signaling pathways involved in tumor development have allowed the development of novel targeted therapies. However, due to the lack of prognostic molecular markers to identify high-risk patients and the absence of a common pathogenesis in all patients, treatment selection is often empirical. There is therefore a need to establish a consensus for the treatment of this disease and to provide evidence-based clinical recommendations and algorithms to optimize and individualize the treatment and follow-up for these patients.
    • Expert consensus on neoadjuvant immunotherapy for non-small cell lung cancer

      Liang, W.; Cai, K.; Chen, C.; Chen, H.; Chen, Q.; Fu, J.; Hu, J.; Jiang, T.; Jiao, W.; Li, S.; et al. (2020)
      None
    • Expert consensus on perioperative immunotherapy for local advanced non-small cell lung cancer

      Qiu, B.; Cai, K.; Chen, C.; Chen, J.; Chen, K. N.; Chen, Q. X.; Cheng, C.; Dai, T. Y.; Fan, J.; Fan, Z.; et al. (2021)
    • Expert Consensus on the Management of Adverse Events from EGFR Tyrosine Kinase Inhibitors in the UK.

      Califano, Raffaele; Tariq, Noor-Ul-Ain; Compton, S; Fitzgerald, D; Harwood, C; Lal, R; Lester, J; McPhelim, J; Mulatero, C; Subramanian, S; et al. (2015-07-18)
      Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and afatinib are standard-of-care for first-line treatment of EGFR-mutant advanced non-small cell lung cancer (NSCLC). These drugs have a proven benefit in terms of higher response rate, delaying progression and improvement of quality of life over palliative platinum-based chemotherapy. The most common adverse events (AEs) are gastrointestinal (GI) (diarrhoea and stomatitis/mucositis) and cutaneous (rash, dry skin and paronychia). These are usually mild, but if they become moderate or severe, they can have a negative impact on the patient's quality of life (QOL) and lead to dose modifications or drug discontinuation. Appropriate management of AEs, including prophylactic measures, supportive medications, treatment delays and dose reductions, is essential. A consensus meeting of a UK-based multidisciplinary panel composed of medical and clinical oncologists with a special interest in lung cancer, dermatologists, gastroenterologists, lung cancer nurse specialists and oncology pharmacists was held to develop guidelines on prevention and management of cutaneous (rash, dry skin and paronychia) and GI (diarrhoea, stomatitis and mucositis) AEs associated with the administration of EGFR-TKIs. These guidelines detail supportive measures, treatment delays and dose reductions for EGFR-TKIs. Although the focus of the guidelines is to support healthcare professionals in UK clinical practice, it is anticipated that the management strategies proposed will also be applicable in non-UK settings.
    • Expert consensus on the management of erlotinib-associated cutaneous toxicity in the u.k.

      Thatcher, Nick; Nicolson, Marianne; Groves, Richard W; Steele, Jeremy; Eaby, Beth; Dunlop, Joyce; McPhelim, John; Nijjar, Rajinder; Ukachukwu, Ijeoma; Department of Medical Oncology, Manchester, M20 4BX, UK. nick.thatcher@christie-tr.nwest.nhs.uk (2009-08)
      Rash has been reported in up to 76% of patients with lung cancer who have received the epidermal growth factor receptor inhibitor (EGFRI) erlotinib. It has also been observed in patients treated with other agents that have a similar mode of action. Erlotinib-associated skin toxicity typically presents as a papulopustular, follicular, acneiform rash. In most cases, it is mild, transient, and well tolerated, but in 8%-12% of patients, it may be sufficiently severe and persistent to necessitate intervention. Increasingly strong data suggest that the incidence and severity of skin toxicity may be predictive of response and survival in patients treated with erlotinib. This has prompted some clinicians to consider "treatment to rash" (i.e., increasing the dosage until a rash appears) as a rational management strategy. In 2007, an international consensus was developed for the management of EGFRI-associated skin toxicity. Subsequently, a multidisciplinary group (the U.K. Erlotinib Skin Toxicity Management Consensus Group) met to validate and modify the international recommendations for U.K. use, with specific reference to erlotinib. Although many aspects of the international consensus were approved by the group as being relevant for the U.K., certain parts were modified. The resulting expert opinion is a practical and workable version of the international proposal that considers all applicable national issues regarding the management of erlotinib-associated skin toxicity.
    • Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk.

      Barrett-Lee, P J; Dixon, J M; Farrell, Carole; Jones, A; Leonard, R; Murray, N; Palmieri, C; Plummer, C J; Stanley, A; Verrill, Mark W; et al. (2009-05)
      Anthracyclines are considered to be among the most active agents for the treatment of breast cancer. However, their use is limited by cumulative, dose-related cardiotoxicity. Such cardiotoxicity results in a permanent loss of cardiac myocytes and a progressive reduction in cardiac function following each subsequent dose of anthracycline. Initially, damage to the heart is subclinical; however, increasingly impaired cardiac function can result in cardiovascular symptoms, with serious cardiac injury resulting in chronic heart failure. Since the early detection and treatment of cardiotoxicity can reduce its clinical effects, it is important that oncologists are aware of these adverse effects and manage them appropriately. This review examines the risk factors for anthracycline-associated cardiotoxicity and offers recommendations on strategies to reduce the cardiotoxicity of anthracyclines in the management of patients with advanced breast cancer.
    • Exploiting biological and physical determinants of radiotherapy toxicity to individualise treatment.

      Scaife, J; Barnett, G; Noble, D; Jena, R; Thomas, S; West, Catharine M L; Burnet, N; University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Road, Cambridge, (2015-05-26)
      The recent advances in radiation delivery can improve tumour control probability and reduce treatment related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day-to-day. Daily image guidance scans can be used to identify the position of normal tissue structures, and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues which limits radiotherapy dose and therefore tumour control. However, the dose response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of radiotherapy. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be due to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In prostate cancer patients receiving curative radiotherapy, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses (EUDs) was -2.7 Gy (5%), and a dose reduction was seen in 7/10 cases. If dose escalation were performed to take rectal dose back to the planned level, this should increase the mean tumour control probability (TCP) (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical radiotherapy who might benefit from either dose escalation, suggesting improved tumour cure, or reduced toxicity, or both.
    • Exploiting biological and physical determinants of radiotherapy toxicity to individualize treatment.

      Scaife, J; Barnett, G; Noble, D; Jena, R; Thomas, S; West, Catharine M L; Burnet, N; University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK (2015-07)
      The recent advances in radiation delivery can improve tumour control probability (TCP) and reduce treatment-related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally, IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day to day. Daily image guidance scans can be used to identify the position of normal tissue structures and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues that limits radiotherapy (RT) dose and therefore tumour control. However, the dose-response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of RT. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be owing to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In patients with prostate cancer receiving curative RT, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses was -2.7 Gy (5%), and a dose reduction was seen in 7 of the 10 cases. If dose escalation was performed to take rectal dose back to the planned level, this should increase the mean TCP (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical RT who might benefit from either dose escalation, suggesting improved tumour cure or reduced toxicity or both.
    • An exploration of food and the lived experience of individuals after treatment for colorectal cancer using a phenomenological approach.

      Burden, S T; Stamataki, Zoe; Hill, J; Molasiotis, A; Todd, C; School of Nursing Midwifery and Social Work, University of Manchester, Manchester (2016-04)
      There is a paucity of qualitative literature investigating people's experiences of food and nutrition after treatment for cancer. The present study aimed to explore people's relationships with food and nutrition throughout their colorectal cancer journey.
    • An exploration of healthcare-related locus of control in COPD patients attending group-based pulmonary rehabilitation

      Edwards, D; Yorke, Janelle; Department of Health Professions, Manchester Metropolitan University, Manchester; Department of Health Professions, Manchester Metropolitan University, Manchester, UK; The University of Manchester and The Christie NHS Foundation Trust, School of Nursing, Midwifery and Social Work, Manchester, UK (2016-12-30)
    • Exploratory analysis of brentuximab vedotin plus CHP (A plus CHP) as frontline treatment for patients with CD30-expressing PERIPHERAL T-cell lymphomas (Echelon-2): impact of consolidative stem cell transplant

      Trneny, M.; Savage, K. J.; Horwitz, S. M.; Advani, R.; Christensen, J. H.; Domingo-Domenech, E.; Rossi, G.; Morschhauser, F.; Alpdogan, O.; Suh, C.; et al. (2020)
      Background: ECHELON-2 (NCT01777152) demonstrated significantly longer progression-free survival (PFS) and overall survival with brentuximab vedotin plus cyclophosphamide, doxorubicin and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) as frontline treatment for patients with sALCL or other CD30-expressing PTCL. Patients could have received consolidative stem cell transplant (SCT) after treatment at the discretion of the treating investigator. Only 22% (50/226) of all patients treated with A+CHP underwent SCT. We present outcomes from an exploratory analysis of patients in complete remission (CR) following A+CHP who received an SCT and those who did not. Methods: CR rate was defined at the end of treatment (EOT) by independent review per the Revised Response Criteria for Malignant Lymphoma. ALK+ sALCL patients were excluded. Consolidative transplant was not considered a PFS event. Univariate analysis of SCT versus no SCT and multivariate analyses adjusting for region and age were performed. Results: 67% (76/113) of A+CHP-treated patients with ALK- sALCL were in CR at EOT; 36% (27/76) of them received SCT. Patients who underwent SCT were younger than those without (median age [range]: 50 years [18-68] versus 59 [20-85] years). Median PFS for patients with SCT was not reached (95% CI: 36.57, not estimable [NE]) versus 55.66 months (95% CI: 23.72, 55.66) for patients without SCT. 59% (38/64) of A+CHP-treated patients with nonsALCL were in CR at EOT; 29% (11/38) of them received SCT. Patients who underwent SCT were younger than those without (median age [range] 57 years [35-73] versus 66 years [49-77]). Median PFS for patients who did and did not receive SCT was not reached (95% CI: 20.70, NE) versus 33.22 months (95% CI: 8.08, NE), respectively. Before treatment, the intent to transplant in Asian countries among ALK- sALCL and non-ALCL patients was less frequent compared to non-Asian countries (13% and 29% versus 49% and 57%, respectively). SCT use was also less frequent in Asia (13% and 12%) versus non-Asian countries (32% and 23%). Standard PFS and multivariate proportional hazards regression analyses favoured SCT use in PTCL patients in CR after A+CHP
    • Exploratory analysis of retreatment with brentuximab vedotin (BV) after frontline treatment with brentuximab vedotin and CHP (A plus CHP) for patients (pts) with CD30+peripheral T-cell lymphoma (ECHELON-2)

      Trumper, L.; Pro, B.; Horwitz, S.; O'Connor, O.; Tilly, H.; Choi, I.; Gritti, G.; Fox, C.; Alpdogan, O.; Mayer, J.; et al. (2020)
      Introduction: Retreatment of pts with relapsed CD30+ Hodgkin lymphoma or systemic anaplastic large cell lymphoma (sALCL) with BV monotherapy showed encouraging antitumor activity (Bartlett 2014). We report exploratory analyses of pts in the phase 3 ECHELON-2 study (NCT01777152) retreated with BV after frontline BV + cyclophosphamide, doxorubicin, and prednisone (A+CHP). Methods: In ECHELON-2, data on subsequent anticancer therapies were collected, including BV-based regimens, after frontline A+CHP or CHP+vincristine. Investigator response assessments used the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Safety data were not collected for subsequent anticancer therapy. Results: In total, 10% of A+CHP pts (23/226) were retreated with BV after PD (median age 62 yrs [range 26-77]). Most had ALK- sALCL (16/23 [70%]). Objective response rate (best response) per investigator (INV) after frontline A+CHP was 91% (21/23 [15 CR, 6 PR]); 2 pts (9%) had a best response of SD. Thirteen pts (57%) received consolidative stem cell transplant (SCT) after frontline therapy, 6 pts (26%) received intervening therapy before BV retreatment. In most pts (19/23 [83%]), first retreatment was BV monotherapy. Median time from frontline therapy to retreatment was 12.3 mos (range 3-50). ORR per INV after initial BV retreatment was 57% (13/23 [10 CR, 3 PR]) (Table). Median duration of initial BV retreatment was 2.1 mos (range 0-18). Four pts who had a CR with frontline A+CHP received >1 subsequent retreatment with BV. Of these, 2 pts had a CR after initial BV retreatment, 1 pt had PD after initial BV retreatment and a CR after allo- SCT and subsequent BV retreatment, and 1 pt had a CR after 3 subsequent BV retreatments. Conclusions: In this post-hoc analysis of ECHELON-2 pts who were retreated with BV after frontline A+CHP, 57% had an objective response to BV retreatment in first relapse. Therefore BV retreatment is active in relapsed treatment even after relapsed treatment.
    • An exploratory study into the influences on patient satisfaction within the lung cancer population

      Boyd, S; Booth, J; Finney, R; The Christie NHS Foundation Trust, Manchester (2020)
      Introduction: The King’s Fund states that patient satisfaction and engagement are inextricably linked. A positive relationship can foster a sense of user engagement; thus helping people who have lost a degree of agency in their life due to a cancer diagnosis reclaim some control. A 2018–19 National Institute for Health Research patient satisfaction survey showed 80% of patients at The Christie had a positive experience. However, the average for the UKs 15 Clinical Research Networks was 90%. This highlights scope for further service improvement. Methods: We plan to use an accredited patient satisfaction tool to focus in on the nature of the interactions between our lung cancer patients participating in clinical trials and all departments of The Christie over a period of six months. This will allow us to delve deeper into the issues facing our service users and highlight the areas in which we can add value to their experience. Results: The Christie is a large organisation consisting of many departments shaping the everyday experience of its service users. All of these interactions impact upon the end-to-end journey of the patient, exerting a positive as well as negative influence on how they view the service. Narrowing in on the various aspects of these interactions can show us how best to support patients with lung cancer who are participating in clinical trials as they navigate through an often stressful and emotional period. Conclusion: The opportunity to improve how we interact with our lung trial patients has wider implications for not just other patients participating in studies but anyone who uses The Christie. The recommendations that come from the findings of this survey can have a positive impact upon all service users and raise awareness amongst staff of the influence and value of all interactions within the Trust.
    • Exploring prostate progenitor compartment complexity as a route of targeting prostate cancer heterogeneity.

      Barros-Silva, Joao D; Linn, D; Guo, G; Steiner, I; Pakula, H; Ashton, Garry; Clarke, Noel W; Yuan, G; Orkin, S; Li, Z; et al. (2018)