The impact of transportation mode, socioeconomic deprivation and rurality on travel times to radiotherapy and surgical services for patients with prostate cancer: A national population-based evaluation.

BACKGROUND: The distances that patients have to travel can influence their access to cancer treatment. We investigated the determinants of travel time, separately for journeys by car and public transport, to centres providing radical surgery or radiotherapy for prostate cancer. METHODS: Using national cancer registry records linked to administrative hospital data, we identified patients who had radical surgery or radiotherapy for prostate cancer between January 2017 and December 2018 in the English National Health Service. Estimated travel times from the patients' residential area to the nearest specialist surgical or radiotherapy centre were estimated for journeys by car and by public transport. RESULTS: We included 13,186 men who had surgery and 26,581 who had radiotherapy. Estimated travel times by public transport (74.4 mins for surgery and 69.4 mins for radiotherapy) were more than twice as long as by car (33.4 mins and 29.1mins, respectively). Patients living in more socially deprived neighbourhoods in rural areas had the longest travel times to the nearest cancer treatment centres by car (62.0 mins for surgery and 52.1 mins for radiotherapy). Conversely patients living in more affluent neighbourhoods in urban conurbations had the shortest (18.7 mins for surgery and 17.9 mins for radiotherapy). CONCLUSION: Travel times to cancer centres vary widely according to mode of transport, socioeconomic deprivation, and rurality. Policies changing the geographical configuration of cancer services should consider the impact on the expected travel times both by car and by public transport to avoid enhancing existing inequalities in access to treatment and patient outcomes.

The future of cancer care in the UK-time for a radical and sustainable National Cancer Plan.

Cancer affects one in two people in the UK and the incidence is set to increase. The UK National Health Service is facing major workforce deficits and cancer services have struggled to recover after the COVID-19 pandemic, with waiting times for cancer care becoming the worst on record. There are severe and widening disparities across the country and survival rates remain unacceptably poor for many cancers. This is at a time when cancer care has become increasingly complex, specialised, and expensive. The current crisis has deep historic roots, and to be reversed, the scale of the challenge must be acknowledged and a fundamental reset is required. The loss of a dedicated National Cancer Control Plan in England and Wales, poor operationalisation of plans elsewhere in the UK, and the closure of the National Cancer Research Institute have all added to a sense of strategic misdirection. The UK finds itself at a crossroads, where the political decisions of governments, the cancer community, and research funders will determine whether we can, together, achieve equitable, affordable, and high-quality cancer care for patients that is commensurate with our wealth, and position our outcomes among the best in the world. In this Policy Review, we describe the challenges and opportunities that are needed to develop radical, yet sustainable plans, which are comprehensive, evidence-based, integrated, patient-outcome focused, and deliver value for money.

First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody.

With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8+ T cell biodistribution in humans. A 89Zr-labeled CD8-targeted minibody (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals (N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients (N = 5). Kinetic modeling results aligned with T cell-trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates and peripheral blood flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory.

First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody.

With the majority of CD8+ T cells residing and functioning in tissue, not blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics in humans offers the means for studying their key role in adaptive immune response and memory. This study is the first report on using positron emission tomography (PET) dynamic imaging and compartmental kinetic modeling for in vivo measurement of whole-body biodistribution of CD8+ T cells in human subjects. For this, a 89Zr-labeled minibody with high affinity for human CD8 (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy subjects (N=3) and in COVID-19 convalescent patients (N=5). The high detection sensitivity, total-body coverage, and the use of dynamic scans enabled the study of kinetics simultaneously in spleen, bone marrow, liver, lungs, thymus, lymph nodes, and tonsils, at reduced radiation doses compared to prior studies. Analysis and modeling of the kinetics was consistent with T cell trafficking effects expected from immunobiology of lymphoid organs, suggesting early uptake in spleen and bone marrow followed by redistribution and delayed increasing uptake in lymph nodes, tonsils, and thymus. Tissue-to-blood ratios from the first 7 h of CD8-targeted imaging showed significantly higher values in the bone marrow of COVID-19 patients compared to controls, with an increasing trend between 2 and 6 months post-infection, consistent with net influx rates obtained by kinetic modeling and flow cytometry analysis of peripheral blood samples. These results provide the platform for using dynamic PET scans and kinetic modelling to study total-body immunological response and memory.

Total-body imaging: Transforming the role of positron emission tomography.

The first total-body positron emission tomography (TB-PET) scanner represents a radical change for experimental medicine and diagnostic health care.

Development and experimental medicine applications of PET in oncology: a historical perspective.

Nearly 90 years of scientific research have led to the use of PET and the ability to forge advances in the field of oncology. In this Historial Review we outline the key developments made with this imaging technique, including the evolution of cyclotrons and scanners, together with the associated advances made in image reconstruction, presentation, analysis of data, and radiochemistry. The applications of PET to experimental medicine are summarised, and we cover how these are related to the use and development of PET, especially in the assessment of tumour biology and pharmacology. The use of PET in clinical oncology and for tissue pharmacokinetic and pharmacodynamic studies as a means of supporting drug development is detailed. The current limitations of the technology are also discussed.

Radionuclide imaging of perfusion and hypoxia.

PURPOSE: We present a review of radionuclide imaging of tumour vascular physiology as it relates to angiogenesis. We focus on clinical trials in human subjects using PET and SPECT to evaluate tumour physiology, in particular blood flow and hypoxia. METHODS: A systematic review of literature based on MEDLINE searches updated in February 2010 was performed. RESULTS: Twenty-nine studies were identified for review: 14 dealt with (15)O-water PET perfusion imaging, while 8 dealt with (18)F-fluoromisonidazole PET hypoxia imaging. Five used SPECT methods. The studies varied widely in technical quality and reporting of methods. CONCLUSIONS: A subset of radionuclide methods offers accurate quantitative scientific observations on tumour vascular physiology of relevance to angiogenesis and its treatment. The relationship between cellular processes of angiogenesis and changing physiological function remains poorly defined. The promise of quantitative functional imaging at high specificity and low administered dose sustains interest in radionuclide methods.

An efficient synthetic strategy for obtaining 4-methoxy carbon isotope labeled combretastatin A-4 phosphate and other Z-combretastatins.

Human cancer and other clinical trials under development employing combretastatin A-4 phosphate (1b, CA4P) should benefit from the availability of a [(11)C]-labeled derivative for positron emission tomography (PET). In order to obtain a suitable precursor for addition of a [(11)C]methyl group at the penultimate step, several new synthetic pathways to CA4P were evaluated. Geometrical isomerization (Z to E) proved to be a challenge, but it was overcome by development of a new CA4P synthesis suitable for 4-methoxy isotope labeling.

Imaging angiogenesis.

There is a need for direct imaging of effects on tumor vasculature in assessment of response to antiangiogenic drugs and vascular disrupting agents. Imaging tumor vasculature depends on differences in permeability of vasculature of tumor and normal tissue, which cause changes in penetration of contrast agents. Angiogenesis imaging may be defined in terms of measurement of tumor perfusion and direct imaging of the molecules involved in angiogenesis. In addition, assessment of tumor hypoxia will give an indication of tumor vasculature. The range of imaging techniques available for these processes includes positron emission tomography (PET), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), perfusion computed tomography (CT), and ultrasound (US).

Rectal motion can reduce CTV coverage and increase rectal dose during prostate radiotherapy: A daily cone-beam CT study.

BACKGROUND AND PURPOSE: Daily on-treatment verification cone-beam CT (CBCT) was used to study the effect of rectal motion on clinical target volume (CTV) coverage during prostate radiotherapy. MATERIAL AND METHODS: CBCT scans were acquired from 15 patients immediately after daily treatment. From these images, the rectum was contoured allowing the analysis of rectal volume cross-sectional area (CSA) and the determination of rectal dose. Rectal wall motion was quantified as a surrogate measure of prostate displacement and CTV coverage was subjectively assessed. RESULTS: Rectal volume decreased over the treatment course in 13 patients (P<0.001). Rectal wall regions corresponding to the prostate base displayed the greatest motion; larger displacements were seen in patients with larger rectal planning volumes. CTV coverage was inadequate, at the prostate base only, in 38% of the fractions delivered to 4/7 patients with a large rectum at planning (>100 cm(3)). In patients with small rectum at planning (<50 cm(3)) up to 25% more rectal volume than predicted was included in the high-dose region. CONCLUSIONS: Rectal motion during treatment in prostate cancer patients has implications for CTV coverage and rectal dose. Measures to ensure consistency in daily rectal volume or image-guided strategies should be considered.