Publications by authors named "Katie Spencer"

15 Publications

  • Page 1 of 1

Low dose pembrolizumab in the treatment of advanced non-small cell lung cancer.

Int J Cancer 2021 Feb 26. Epub 2021 Feb 26.

Department of Haematology-Oncology, National University Cancer Institute, Singapore.

A dose of 200mg 3-weekly of pembrolizumab was approved by the FDA as treatment for advanced NSCLC without oncogenic drivers. This is despite evidence showing no difference in efficacy with 2mg/kg. This study aimed to assess the efficacy of a lower fixed dose of 100mg, which is closer to 2mg/kg weight-based dose in an average sized Asian patient. All patients receiving pembrolizumab for advanced NSCLC from January 2016 to March 2020 in National University Hospital, Singapore, were included in this retrospective observational study. The effect of pembrolizumab 100mg (Pem100) versus 200mg (Pem200) upon survival outcomes, toxicity and cost were examined. 114 patients received pembrolizumab. 65 (57%) and 49 (43%) received Pem100 and Pem200 respectively. There was no difference in progression-free survival (PFS) and overall survival (OS) between Pem100 vs Pem200 as a single agent (PFS: 6.8 vs 4.2months, HR 0.72, 95%CI 0.36-1.46, p=0.36; 9 month OS: 58% vs 63%, HR 1.08, 95%CI 0.48-2.41, p=0.86) and when combined with chemotherapy (9-month PFS: 60% vs 50%, HR0.84, 95%CI0.34-2.08, p=0.71; 9-month OS: 85% vs 58%, HR 0.27, 95%CI 0.062-1.20, p=0.09). No significant difference in response rate or ≥G3 immune-related toxicities between Pem100 and Pem200 was observed. A cost minimisation analysis evaluating the degree of cost savings related to drug costs estimated a within study cost saving of SGD4,290,912 and cost saving per patient of SGD39,942 in the Pem100 group. 100mg of pembrolizumab appears to be effective with reduction in cost. A randomised trial should be done to investigate a lower dose of pembrolizumab.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33534DOI Listing
February 2021

The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study.

Lancet Oncol 2021 Jan 22. Epub 2021 Jan 22.

Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: The indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England.

Methods: In this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis.

Findings: In 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances.

Interpretation: Radiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences.

Funding: None.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(20)30743-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825861PMC
January 2021

Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study.

Lancet Gastroenterol Hepatol 2021 03 15;6(3):199-208. Epub 2021 Jan 15.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK.

Background: There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England.

Methods: Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated.

Findings: As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53-71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89-95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8-34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19-42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17-76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020.

Interpretation: The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England.

Funding: Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2468-1253(21)00005-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808901PMC
March 2021

Commentary on Cost-Effectiveness of Metastasis-Directed Therapy in Oligorecurrent Hormone-Sensitive Prostate Cancer.

Int J Radiat Oncol Biol Phys 2020 Nov;108(4):927-929

The Royal Marsden NHS Foundation Trust, London, United Kingdom The Institute of Cancer Research, London, United Kingdom.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2020.08.021DOI Listing
November 2020

Collection of routine cancer data from private health-care providers.

Lancet Oncol 2019 09;20(9):1202-1204

Cancer Epidemiology Group, University of Leeds, Leeds LS9 7TF, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(19)30545-5DOI Listing
September 2019

Net Pain Relief After Palliative Radiation Therapy for Painful Bone Metastases: A Useful Measure to Reflect Response Duration? A Further Analysis of the Dutch Bone Metastasis Study.

Int J Radiat Oncol Biol Phys 2019 11 22;105(3):559-566. Epub 2019 Jul 22.

Department of Radiotherapy, Leiden University Medical Centre, Leiden, The Netherlands.

Purpose: Pain response rates are equivalent after single 8 Gy and fractionated palliative radiation therapy for bone metastases. Reirradiation remains more frequent after a single fraction, although this does not simply reflect pain recurrence. Given the possible role of stereotactic radiation therapy in providing durable pain control, measures of durability are required. Net pain relief (NPR), the proportion of remaining life spent with pain response, may provide this. This study assesses the use of NPR as an outcome measure after palliative radiation therapy for bone metastases.

Methods And Materials: This is a secondary analysis of data collected in the Dutch Bone Metastasis Study, a randomized trial comparing palliative radiation therapy delivered as 8 Gy in a single fraction and 24 Gy in 6 fractions. NPR was assessed by survival cohorts, treatment regimen, and primary diagnoses. The consequences of missing data upon the use of NPR in future studies were considered within sensitivity analyses.

Results: Patients whose pain improved after palliative radiation therapy experienced improvement for 56.6% of their remaining lives. Missing responses in questionnaires mean the range of uncertainty in NPR is 36.1% to 62.1%. When response beyond reirradiation was excluded, NPR after treatments of single-fraction 8 Gy and 24 Gy in 6 fractions was 49.0% and 56.5%, respectively (P = .004). Differential willingness to reirradiate may be influencing this outcome. When response beyond reirradiation was included, this difference was not seen (NPR of 55.4% vs 57.7%, respectively [P = .191]).

Conclusions: Patients who responded to conventional radiation therapy experienced improved pain control for approximately half of their remaining life. NPR may provide valuable information in assessing pain response durability. Missing data are, however, inevitable in this population. This must be minimized and the consequences recognized and reported. Additionally, reirradiation protocols and the frequency and duration of trial follow-up may have a significant impact upon this outcome, requiring careful consideration during trial design if NPR is to be used in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2019.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859481PMC
November 2019

Systematic Review of the Role of Stereotactic Radiotherapy for Bone Metastases.

J Natl Cancer Inst 2019 10;111(10):1023-1032

Background: Stereotactic radiotherapy (SBRT) might improve pain and local control in patients with bone metastases compared to conventional radiotherapy, although an overall estimate of these outcomes is currently unknown.

Methods: A systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pubmed, Embase, and Cochrane databases were systematically searched to identify studies reporting pain response and local control among patients with bone metastases from solid-organ tumors who underwent SBRT in 1-6 fractions. All studies prior to April 15, 2017, were included. Study quality was assessed by predefined criteria, and pain response and local control rates were extracted.

Results: A total of 2619 studies were screened; 57 were included (reporting outcomes for 3995 patients) of which 38 reported pain response and 45 local control rates. Local control rates were high with pain response rates above those previously reported for conventional radiotherapy. Marked heterogeneity in study populations and delivered treatments were identified such that quantitative synthesis was not appropriate. Reported toxicity was limited. Of the pain response studies, 73.7% used a retrospective cohort design and only 10.5% used the international consensus endpoint definitions of pain response. The median survival within the included studies ranged from 8 to 30.4 months, suggesting a high risk of selection bias in the included observational studies.

Conclusions: This review demonstrates the potential benefit of SBRT over conventional palliative radiotherapy in improving pain due to bone metastases. Given the methodological limitations of the published literature, however, large randomized trials are now urgently required to better quantify this benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djz101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792073PMC
October 2019

Rectal cancer in old age -is it appropriately managed? Evidence from population-based analysis of routine data across the English national health service.

Eur J Surg Oncol 2019 Jul 7;45(7):1196-1204. Epub 2019 Jan 7.

Cancer Epidemiology Group, Leeds Institute for Data Analytics, Worsley Building, University of Leeds, LS2 9NL, UK.

Background: There is significant debate as to where to draw the line between undertreating older rectal cancer patients and minimising treatment risks. This study sought to examine the use of radical rectal cancer treatments and associated outcomes in relation to age across the English NHS.

Methods: Patient, tumour and treatment characteristics for all patients diagnosed with a first primary rectal cancer in England between 1st April 2009 and 31st December 2014 were obtained from the CORECT-R data repository. Descriptive analyses and adjusted logistic regression models were undertaken to examine any association between age and the use of major resection and post-surgical outcomes. Funnel plots were used to show variation in adjusted rates of major resection.

Results: The proportion of patients who underwent a major surgical resection fell from 66.5% to 31.7%, amongst those aged <70 and aged ≥80 respectively. After adjustment, 30-day post-operative mortality, failure to rescue and prolonged length of stay were significantly higher among the oldest group when compared to the youngest. Patient reported outcomes were not significantly worse amongst older patients. Significant variation was observed in adjusted surgical resection rates in the oldest patients between NHS Trusts. The probability of death due to cancer was comparable across all age groups.

Conclusions: Older patients who are selected for surgery have good outcomes, often comparable to their younger counterparts. Significant variation in the treatment of older patients could not be explained by differences in measured characteristics and required further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejso.2019.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602152PMC
July 2019

Surgery or radiotherapy for stage I lung cancer? An intention-to-treat analysis.

Eur Respir J 2019 06 20;53(6). Epub 2019 Jun 20.

Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Introduction: Surgery is the standard of care for early-stage lung cancer, with stereotactic ablative body radiotherapy (SABR) a lower morbidity alternative for patients with limited physiological reserve. Comparisons of outcomes between these treatment options are limited by competing comorbidities and differences in pre-treatment pathological information. This study aims to address these issues by assessing both overall and cancer-specific survival for presumed stage I lung cancer on an intention-to-treat basis.

Methods: This retrospective intention-to-treat analysis identified all patients treated for presumed stage I lung cancer within a single large UK centre. Overall survival, cancer-specific survival, and combined cancer and treatment-related survival were assessed with adjustment for confounding variables using Cox proportional hazards and Fine-Gray competing risks analyses.

Results: 468 patients (including 316 surgery and 99 SABR) were included in the study population. Compared with surgery, SABR was associated with inferior overall survival on multivariable Cox modelling (SABR HR 1.84 (95% CI 1.32-2.57)), but there was no difference in cancer-specific survival (SABR HR 1.47 (95% CI 0.80-2.69)) or combined cancer and treatment-related survival (SABR HR 1.27 (95% CI 0.74-2.17)). Combined cancer and treatment-related death was no different between SABR and surgery on Fine-Gray competing risks multivariable modelling (subdistribution hazard 1.03 (95% CI 0.59-1.81)). Non-cancer-related death was significantly higher in SABR than surgery (subdistribution hazard 2.16 (95% CI 1.41-3.32)).

Conclusion: In this analysis, no difference in cancer-specific survival was observed between SABR and surgery. Further work is needed to define predictors of outcome and help inform treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.01568-2018DOI Listing
June 2019

Variation in geographical treatment intensity affects survival of non-small cell lung cancer patients in England.

Cancer Epidemiol 2018 12 27;57:13-23. Epub 2018 Sep 27.

National Cancer Registration and Analysis Service, Public Health England, Wellington House, London, UK; Department of Cancer Epidemiology, Population and Global Health, Division of Cancer Studies, Faculty of Life Sciences & Medicine, King's College London, London, UK. Electronic address:

Objectives: We aimed to determine the geographical variation in the proportion of non-small cell lung cancer (NSCLC) patients undergoing curative treatment and assess the relationship between treatment access rates and survival outcomes.

Methods: We extracted cancer registration data on 144,357 lung cancer (excluding small cell tumours) patients diagnosed between 2009 and 2013. Surgical and radiotherapy treatment intensity quintiles were based on patients' Clinical Commissioning Group (CCG) of residence. We used logistic regression to assess the effect of travel time and case-mix on treatment use and Cox regression to analyse survival in relation to treatment intensity.

Results: There was wide variation in the use of curative treatment across CCGs, with the proportion undergoing surgery ranging from 8.9% to 20.2%, and 0.4% to 16.4% for radical radiotherapy. The odds of undergoing surgery decreased with socioeconomic deprivation (OR 0.91, 95% CI 0.85-0.97), whereas the opposite was observed for radiotherapy (OR 1.16, 95% CI 1.08-1.25). There was an overall effect of travel time to thoracic surgery centre on the odds of undergoing surgery (OR 0.81, 95% CI 0.76-0.87 for travel time >55 min vs ≤15 min) which was amplified by the effect of deprivation. No clear association was observed for radiotherapy. Higher mortality rates were observed for the lower resection and radiotherapy quintiles (HR 1.08, 95% CI 1.04-1.12 and HR 1.06, 95% CI 1.02-1.10 for lowest vs. highest resection and radiotherapy quintile).

Conclusion: There was wide geographical variation in the use of curative treatment and a higher frequency of treatment was associated with better survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canep.2018.09.001DOI Listing
December 2018

Palliative radiotherapy.

BMJ 2018 03 23;360:k821. Epub 2018 Mar 23.

Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS2 9NL, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865075PMC
http://dx.doi.org/10.1136/bmj.k821DOI Listing
March 2018

Improving diabetes care at the end of life.

Nurs Stand 2015 Oct;30(6):37-42

Royal Trinity Hospice, London, England.

The number of people with diabetes in the UK is increasing. Many are aged over 75 years, and this has resulted in rising numbers of patients for whom diabetes exists comorbidly with other disease processes. Those with life-limiting illness require palliative care services. However, end of life care for patients with diabetes is generally poor. The aim of end of life care for these individuals is to maintain comfort, while minimising the risks of osmotic symptoms. The wishes of patients, carers and families should be taken into consideration when agreeing new glucose control targets, adjusting treatment or changing focus on diet. Patients and carers should feel that the condition is being managed with the support of healthcare professionals. These professionals need the knowledge, skills and confidence to recognise the end of life to tailor diabetes care appropriately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7748/ns.30.6.37.s45DOI Listing
October 2015

30 day mortality in adult palliative radiotherapy--A retrospective population based study of 14,972 treatment episodes.

Radiother Oncol 2015 May 7;115(2):264-71. Epub 2015 Apr 7.

St James's Institute of Oncology, Leeds Cancer Centre, St James's University Teaching Hospital, United Kingdom.

Background: 30-day mortality (30DM) has been suggested as a clinical indicator of the avoidance of harm in palliative radiotherapy within the NHS, but no large-scale population-based studies exist. This large retrospective cohort study aims to investigate the factors that influence 30DM following palliative radiotherapy and consider its value as a clinical indicator.

Methods: All radiotherapy episodes delivered in a large UK cancer centre between January 2004 and April 2011 were analysed. Patterns of palliative radiotherapy, 30DM and the variables affecting 30DM were assessed. The impact of these variables was assessed using logistic regression.

Results: 14,972 palliative episodes were analysed. 6334 (42.3%) treatments were delivered to bone metastases, 2356 (15 7%) to the chest for lung cancer and 915 (5.7%) to the brain. Median treatment time was 1day (IQR 1-7). Overall 30DM was 12.3%. Factors having a significant impact upon 30DM were sex, primary diagnosis, treatment site and fractionation schedule (p<0.01).

Conclusion: This is the first large-scale description of 30-day mortality for unselected adult palliative radiotherapy treatments. The observed differences in early mortality by fractionation support the use of this measure in assessing clinical decision making in palliative radiotherapy and require further study in other centres and health care systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2015.03.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504022PMC
May 2015

Brain metastases.

Clin Med (Lond) 2014 Oct;14(5):535-7

St James's Institute of Oncology, Leeds, UK

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7861/clinmedicine.14-5-535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951966PMC
October 2014

Issues in neurological risk assessment for occupational exposures: the Bay Bridge welders.

Neurotoxicology 2006 May 5;27(3):373-84. Epub 2005 Dec 5.

Risk Evaluation Branch, Education and Information Division, NIOSH, Centers for Disease Control and Prevention, Cincinnati, OH 45226, USA.

The goal of occupational risk assessment is often to estimate excess lifetime risk for some disabling or fatal health outcome in relation to a fixed workplace exposure lasting a working lifetime. For sub-chronic or sub-clinical health effects measured as continuous variables, the benchmark dose method can be applied, but poses issues in defining impairment and in specifying acceptable levels of excess risk. Such risks may also exhibit a dose-rate effect and partial reversibility such that effects depend on how the dose is distributed over time. Neurological deficits as measured by a variety of increasingly sensitive neurobehavioral tests represent one such outcome, and the development of a parkinsonian syndrome among welders exposed to manganese fume presents a specific instance. Welders employed in the construction of piers for a new San Francisco-Oakland Bay Bridge in San Francisco were previously evaluated using a broad spectrum of tests. Results for four of those tests (Rey-Osterrieth Complex Figure Test, Working Memory Index, Stroop Color Word Test and Auditory Consonant Trigrams Test) were used in the benchmark dose procedure. Across the four outcomes analyzed, benchmark dose estimates were generally within a factor of 2.0, and decreased as the percentile of normal performance defining impairment increased. Estimated excess prevalence of impairment, defined as performance below the 5th percentile of normal, after 2 years of exposure at the current California standard (0.2 mg/m3, 8 h TWA), ranged 15-32% for the outcomes studied. Because these exposures occurred over a 1-2-year period, generalization to lifetime excess risk requires further consideration of the form of the exposure response and whether short-term responses can be generalized to equivalent 45-year period. These results indicate unacceptable risks at the current OSHA PEL for manganese (5.0 mg/m3, 15 min) and likely at the Cal OSHA PEL as well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuro.2005.10.010DOI Listing
May 2006