ESTRO 2020 Abstract book

S38 ESTRO 2020

implementation period, resulted in a fall to £28,431/QALY. Where these long-term costs were considered in a population with prolonged survival the ICER dropped markedly to £17,889/QALY with SABR having an 80.6% probability of being cost-effective. Conclusion SABR is highly unlikely to be cost-effective at currently commissioned costs and if all patients currently undergoing palliative radiotherapy for bone metastases were considered eligible. This latter limitation results from the limited survival of many patients with bone metastases. Recognition of the learning curve seen in the cost of SABR delivery and careful selection of patients could, however, allow for cost-effective treatment delivery. The efficacy of SABR, demonstrated in early phase trials, must now be replicated in larger, randomised controlled studies if these treatments are to be cost- effective. OC-0080 Radiation therapy increases tumor vulnerability to natural killer cell-mediated control J.I. Sia 1,2 , I. Chindris 1 , J. Hagekyriakou 1 , R. Johnstone 1,2 , N. Haynes 1,2 1 Peter MacCallum Cancer Centre, Cancer Research, Melbourne, Australia ; 2 University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, Australia Purpose or Objective The immune modulatory effects of radiation therapy (RT) on the innate and adaptive arms of the immune system are increasingly recognised to be important. Utilising RT in a manner that supports host anti-cancer immune responses is a paradigm gaining interest, but how best to employ this remains unclear. Here we examine the impact of radiation dose-fractionation on tumor-associated natural killer (NK) cells, which form an important line of host innate immune defense against cancer. From this, we identify ways of better leveraging the therapeutic potential of NK cells with RT and cancer immunotherapy. Material and Methods Established AT3-OVA intra-mammary and MC-38 subcutaneous tumors growing in wildtype C57BL/6 mice were locally irradiated with different radiation dose- fractionations to dissect the effects of radiation dose per fraction (DPF) from total radiation dose (biological effective dose, BED). Depleting antibodies were used to assess the impact of immune subsets on tumor growth post irradiation. Effects on the tumor microenvironment were examined with flow cytometry and RNA sequencing. Such information guided the selection and application of antibody-based checkpoint blockade therapy to promote host innate and adaptive anti-cancer immune defenses . Results Radiation dose-fractionations are not equivalent in their capacity to engage CD8+ T cell and NK cell responses. Treatment with the 3x4Gy, 9x4Gy and 3x8Gy regimens elicited effective CD8+ T cell responses that supported the anti-cancer activity of anti-PD-1 therapy. The high DPF regimen of 1x20Gy, despite having a similar BED to 9x4Gy, was unable to engage effective CD8+ T cell responses. In contrast, only higher BED regimens (36-45Gy) evoked NK cell responses that significantly slowed tumor growth. While all radiation regimens tested promoted an acute increase in tumor-associated NK cell numbers, only the higher BED regimen supported a sustained elevation in tumor-associated NK cell numbers with higher activation markers and corresponding enrichment of the NK cell- mediated cytotoxicity gene signature. The anti-cancer activity of these NK cells is highly sensitive to control by a Proffered Papers: Proffered papers 2: Interactions between radiation and the immune response

Monte Carlo simulations revealed that the mean cost for AM, PR, and RT were $15,654, $18,791, and $30,378, respectively, and QALYs were 6.96, 7.44, and 7.9 years, respectively. The incremental cost-effectiveness ratio (ICER) was $6,548 for PR over AM and $68,339 for RT over PR. Results were sensitive to the number of years of follow-up and procedure cost. With relaxed assumptions for AM, the ICER of PR and RT met the societal willingness to pay (WTP) threshold of $50,000 per QALY. Conclusion Compared with AM, PR was highly cost-effective. RT and PR for localized prostate cancer are cost- effective,however RT in part due to cost of neoadjuvant hormone therapy results lower cost-effectiveness compared to PR. Newer and more effective radiotherapy strategies like stereotactic body radiotherapy alone may play a crucial role in future early prostate cancer management. OC-0079 Can SABR for painful bone metastases ever be cost-effective in the NHS? K. Spencer 1 , C. Bojke 1 , A. Henry 2 , G. Velikova 2 , E. Morris 3 , Y. Van der Linden 4 , W. Van den Hout 5 , P. Hall 6 1 University of Leeds, Leeds Institute of Health Sciences, Leeds, United Kingdom ; 2 University of Leeds, Leeds Institute of Medical Research, Leeds, United Kingdom ; 3 University of Leeds, Leeds Institute of Data Analytics, Leeds, United Kingdom ; 4 Leiden University Medical Centre, Radiotherapy department, Leiden, The Netherlands ; 5 Leiden University Medical Centre, Health Economics, Leiden, The Netherlands ; 6 Edinburgh University, Edinburgh Cancer Research Centre, Edinburgh, United Kingdom Purpose or Objective Higher rates of re-irradiation following single fraction conventional radiotherapy have led to persistent views that dose-escalation might result in better quality and durability of pain control. Single centre series and an early phase trial have demonstrated high rates of complete pain response and durability following stereotactic radiotherapy (SABR). SABR is, however, markedly more expensive than conventional radiotherapy. This study aimed to assess if SABR for painful bone metastases could ever be cost-effective in the English National Health Service (NHS). Material and Methods A Markov decision model was developed to model costs (in 2016 £ sterling) and benefits associated with SABR as compared to single 8Gy conventional palliative radiotherapy. Four pain response states were included, in line with the International Consensus on Palliative Radiotherapy Endpoints (ICPRE). Re-irradiation could occur where pain persisted and death was an absorbing state which could be reached from all pain response states. A life-time horizon was modelled with a cycle length of 1 week. Model parameters were informed using data from the Dutch Bone Metastases Study, literature review and NHS reference costs. Response to SABR was informed based on the outcomes of Sprave et al. One way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model parameters.Specific focus was placed upon the impact of plausible changes in the survival of the treated cohort and treatment costs. Results SABR treatment resulted in an average QALY gain of 0.056 with associated incremental costs of £3125 for a three fraction course. At a willingness to pay threshold of £30,000/QALY the incremental cost-effectiveness ratio (ICER) for SABR was £55,592/QALY with a probability of 4% that SABR was the most cost-effective strategy. In a population with a median survival of 53 weeks, the ICER dropped to £39,200/QALY. Similarly, recognising a plausible long-term cost of treatment, beyond an initial

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