ROBUST RADIOTHERAPY APPOINTMENT SCHEDULING

Optimal scheduling of patients waiting for radiation treatments is a quite challenging operational problem in radiotherapy clinics. Long waiting times for radiotherapy treatments is mainly due to imbalanced supply and demand of radiotherapy services, which negatively affects the effectiveness and efficiency of the healthcare delivered. On the other hand, variations in the time required to set-up machines for each individual patient as well as patient treatment times make this problem even more involved. Efficient scheduling of patients on the waiting list is essential to reduce the waiting time and its possible adverse direct and indirect impacts on the patient. This research is focused on the problem of scheduling patients on a prioritized radiotherapy waiting list while the rescheduling of already booked patients is also possible. The aforementioned problem is formulated as a mixed-integer program that aims for maximizing the number of newly scheduled patients such that treatment time restrictions, scheduling of patients on consecutive days on the same machine, covering all required treatment sessions, as well as the capacity restriction of machines are satisfied. Afterwards, with the goal of protecting the schedule against treatment time perturbations, the problem is reformulated as a cardinality-constrained robust optimization model. This approach provides some insights into the adjustment of the level of robustness of the patients schedule over the planning horizon and protection against uncertainty. Further, three metaheuristics, namely Whale Optimization Algorithm, Particle Swarm Optimization, and Firefly Algorithm are proposed as alternative solution methods. Our numerical experiments are designed based on a case study inspired from a real radiotherapy clinic. The first goal of experiments is to analyze the performance of proposed robust radiotherapy appointment scheduling (ASP) model in terms of feasibility of schedule and the number of scheduled patients by the aid of Monte-Carlo simulation. Our second goal is to compare the solution quality and CPU time of the proposed metaheuristics with a commercial solver. Our experimental results indicate that by only considering half of patients treatment times as worst-case scenario, the schedule proposed by the robust RAS model is feasible in the presence of all randomly generated scenarios for this uncertain parameter. On the other hand, protecting the schedule against uncertainty at the aforementioned level would not significantly reduce the number of scheduled patients. Finally, our numerical results on the three metaheuristics indicate the high quality of their converged solution as well as the reduced CPU time comparing to a commercial solver

The Comprehensive Cancer Center

This open access book provides a valuable resource for hospitals, institutions, and health authorities worldwide in their plans to set up and develop comprehensive cancer care centers. The development and implementation of a comprehensive cancer program allows for a systematic approach to evidence-based strategies of prevention, early detection, diagnosis, treatment, and palliation. Comprehensive cancer programs also provide a nexus for the running of clinical trials and implementation of novel cancer therapies with the overall aim of optimizing comprehensive and holistic care of cancer patients and providing them with the best opportunity to improve quality of life and overall survival. This book's self-contained chapter format aims to reinforce the critical importance of comprehensive cancer care centers while providing a practical guide for the essential components needed to achieve them, such as operational considerations, guidelines for best clinical inpatient and outpatient care, and research and quality management structures. Intended to be wide-ranging and applicable at a global level for both high and low income countries, this book is also instructive for regions with limited resources. The Comprehensive Cancer Center: Development, Integration, and Implementation is an essential resource for oncology physicians including hematologists, medical oncologists, radiation oncologists, surgical oncologists, and oncology nurses as well as hospitals, health departments, university authorities, governments and legislators

Mathematical Model Studies on the Optimal Scheduling of the Treatment of Systemic Malignant Disease by Radiation

The work reported in this thesis deals with mathematical model studies on the optimal scheduling of treatment of systemic malignant disease by radiation. To provide the necessary background to the original aspects of the work reviews of several fields are required. Chapter 1 is a general review of normal tissue radiobiology. Chapter 2 is a review of human tumour radiobiology. Chapter 3 focusses on one particular isoeffect model, the linear-quadratic or LQ model, which is employed throughout this thesis to describe the effects of radiation on normal tissues. These basic radiobiological principles are applied to the clinical modalities of total body irradiation (TBI) and biologically targeted radiotherapy (BTR). Chapter 4 reviews the principles of TBI. Chapter 5 is a review of published data on the in-vitro radiosensitivities of human leukaemia/lymphoma and neuroblastoma, two conditions which require a systemic approach to treatment. Chapter 8 is a review of the principles of BTR. The original work is contained in the appendix to chapter 3, which examines the correspondence between the LQ model and CRE models for continuous radiation exposures with constant and exponentially decaying dose-rates; chapter 6, Which examines the question of whether fractionated or low dose-rate TBI is the superior method of treatment; chapter 7, where the optimal scheduling of fractionated TBI is investigated; chapter 9, where the LQ isoeffect model and a dosimetric approach is used for the evaluation of alternative therapeutic strategies for the treatment of widespread micrornetastatic disease by BTR. Finally, in chapter 10 a simple model is used to investigate optimal scheduling of BTR, TBI and marrow rescue. CONCLUSIONS 1/ Comparison of the LQ model and the CRE model for continuous radiation exposures: for constant dose-rates it is found that, when late-effect parameter values are used in the LQ model, there is a correspondence between the models' predictions. There is no correspondence between models when acute-effect parameter values are used in the LQ model. In the case of exponentially decaying dose-rates the predictions of the CRE and LQ models appear more divergent, although again the use of late rather than acute-effect parameter values in the LQ model gives a closer match to the CRE. 2/ Fractionated TBI is predicted to be preferable to low dose-rate TBI treatment. Although theoretically the methods can be equivalent, low dose-rate treatments would have to be over impractically long treatment times. 3/ In the case of external beam TBI, fractionated low dose-rate treatments do not appear to offer a significant improvement over fractionated high dose-rate treatments. This is because in order to achieve a significant increase in dose or reduction in toxicity impractically long exposure times are required. It is expected that this finding will be true in general for external beam radiotherapy, not just in the case of TBI. 4/ Optimal fractionation schedules for the treatment of leukaemia/lymphoma and neuroblastoma by TBI are predicted to be accelerated and hyperfractionated. It is suggested that a two fraction per day schedule of 10 fractions of 1.3-1.5 Gy is a suitable candidate for clinical evaluation. 5/ It is concluded that knowledge of ratios for tumours and normal tissues is, by itself, insufficient information to enable prediction of optimal schedules. 6/ In the case of BTR, dose-rate effects are predicted to be important for late-responding tissues. Tolerance doses may be greater or less than those for fractionated radiotherapy depending on the effective radionuclide half-life. 7/ When injected activities of targeted radionuclide are restricted by haemopoietic tolerance, curative therapy is unlikely. 131-I appears to be a better radionuclide warhead for therapy of micrometastases than 90-Y. 8/ The use of bone marrow rescue in conjunction with BTR seems to offer curative potential, however reasons are presented why a combined strategy using BTR, TBI and marrow rescue is likely to be preferable. 9/ For optimal scheduling of BTR, TBI and marrow rescue, the main characteristics of BTR which determine curative potential are its specificity and sensitivity. Specificity is defined here as the ratio of initial dose-rate at the tumour cells to that in the dose-limiting tissue. Sensitivity is inversely related to the proportion of tumour cells which escape targeting. Where biological targeting is highly specific but some tumour cells escape, a phenomenon of "overkill" will largely determine the optimal schedules. It is predicted that these are likely to consist of combinations of BTR and external beam TBI with the TBI component being the greatest in terms of radiation dose to the whole body

SPARC 2018 Internationalisation and collaboration : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2018 SPARC conference. This year we not only celebrate the work of our PGRs but also the launch of our Doctoral School, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 100 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to take up this great opportunity to engage with researchers working in different subject areas from your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers

Radiation risks from high-let alpha particle emitters using radium-223 as a model

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London[223Ra]RaCl2 was recently approved for the treatment of bone metastatic disease in prostate cancer patients. Once intravenously administered 223Ra localises to areas of increased calcium turnover. During its decay, 223Ra will emit high linear energy transfer (LET) α-particles that are effective in targeting metastatic sites. α-particles have a range of ≤ 100 μm suggesting normal tissue sparing; however, there is uncertainty regarding the heterogeneous distribution of dose at the cellular/tissue levels. It remains unclear if 223Ra may also result in unwanted exposure of neighbouring bone marrow (BM) cells. To date, the potential risk of BM exposure as a consequence of this treatment remains unquantified. The aim of this project was to resolve these uncertainties by assessing changes in the genomic structure of peripheral blood lymphocyte (PBLs) potentially in contact with 223Ra. To do so, blood samples from patients enrolled on to the ADRRAD clinical trial were collected. The treatment included 6 intravenous injections of [223Ra]RaCl2 each administered 4 weeks apart (55 kbq/kg) and 2 Gy fractionated IMRT (daily for 5 days a week over 7.5 weeks). Blood samples were collected prior to each 223Ra administration and PBL cultured to 1st in vitro division. The PBLs were assayed by Multiplex-fluorescent-in-situ-hybridization (M-FISH) and Giemsa solid stain for cytogenetic analysis. In this study we demonstrated that chromosomal aberration complexity reflects the treatment regime. This indicates PBLs were exposed to α-particle by 223Ra. The change in chromosomal spectrum was used to create a novel method for absorbed blood dose estimation and this was compared to existing physical models. The persistence and transmissibility of aberrations was evaluated with chromatid aberrations consistent with delayed effects observed in follow up samples. A lower administered activity of 223Ra was suggested to be as effective as larger administer activities, this indicates that the dosing strategy may need re-evaluating