ESTRO 2024 - Abstract Book

S21 ESTRO 2024 Results : Using an integrative approach comprising 52,975 SCLC transcriptomes, high-resolution measurement of cell state dynamics at the single cell level, and correlative studies using treatment naïve human-derived xenografts, we show that SCLC tumors are substantially more heterogeneous than previously appreciated, with most samples retaining two or more subpopulations marked by Ascl1, NeuroD1, or Yap1. Intratumoral states or subpopulations confer discrete functional attributes in individual tumors and these states undergo multivalent transitions ( i.e . they are pan-plastic). Measurements of population- and single cell-level state dynamics indicate that SCLC tumors display distinctive equilibria in the proportion of cells within these cellular states and state interconversions represent critical mechanisms for SCLC growth and cell type diversity. Critically, ATAC-seq profiling demonstrates a role for the epigenome in the state diversity of SCLC insofar as there was preferential promoter accessibility to Ascl1, NeuroD1, and Yap1 in a manner consistent with gene and protein expression in the respective subpopulations. New therapeutic strategies including the alternative sequencing of drugs that modulate the epigenome and chemotherapy are shown to direct some SCLC tumors toward improved responses to chemotherapy in human ex vivo cultures and patient derived xenografts. Conclusion : We have elucidated a spectrum of states in SCLC cells and their dynamics, identifying cellular programs that recapitulate neuroendocrine (Ascl1), neural (NeuroD1), and mesenchymal (Yap1) development. Our work advances a model of cellular states and program diversity in SCLC and nominates new therapeutic strategies designed to limit the plasticity, and hence versatility, of this lethal cancer. Invited Speaker

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Challenges and dilemmas in the elderly gynaecological cancer patient

Maja Pakiz

University Medical Center Maribor, Department for Gynecologic and Breast Oncology, Maribor, Slovenia

Abstract:

As the incidence of cancer increases with age and as median age of all Western populations is rising challenges associated with management of elderly cancer patients are frequent and present specific burdens both for the patients and care providers. The presentation will be focused on assessing frailty in gynaecologic oncology population, quality of life in elderly cancer patients, challenges in clinical trials in this population as well as awareness and attitudes of care providers toward treating elderly cancer patients. Age itself in cancer patients may present a risk factor for under-treatment of patients solely due to age. However, it has been shown that frailty (defined as a complex biologic syndrome characterised by decline in multiple organic systems and reduced functional reserve) is more reliable than chronological age in predicting the patients' prognosis and tolerability of therapies. Assessing frailty with Comprehensive Geriatric Assessment (a gold standard for frailty evaluation) is associated with specialist geriatric counselling and is time consuming; both reasons may be associated with development of new tools that are available as screening tools in everyday clinical practise. In the field of gynaecologic oncology we have a recently published data about new suggested tool to assess frailty in this population; the tool assesses both functional status as well as comorbidity. The Table of items are attached (Ferrero A, et al. Int J Gynecol Cancer 2024;34:300-306). The average time to assess frailty with this tool is 6 minutes and the cut off point of 4 or more points is associated with sensitivity of 77% and specificity of 100% to assess frailty and predict complications of oncology treatment, both Grade III/IV complications of surgery and hematological toxicities as well as systemic treatment delay and discontinuation.