ESTRO 38 Abstract book

S112 ESTRO 38

currently deemed as an important mechanism to cell–cell communication, allowing cells to exchange proteins, lipids and genetic material. These vesicles carry molecules such as oncoproteins and oncopeptides, RNA species (e.g., microRNAs, mRNAs, and long non-coding RNAs), lipids, and DNA fragments from donor to recipient cells. These compounds are potential sources of prognostic and/or predictive biomarkers as well as markers of treatment response. We will review the current role of extracellular vesicles in radiation therapy, with a particular focus on the development of clinical assays for treatment personalization. SP-0214 Update on the management of SCLC C. Le Pechoux 1 , A. Botticella 1 , A. Levy 1 1 gustave Roussy Cancer Campus, Radiation Oncology, Villejuif Cedex, France Abstract text Small cell lung cancer (SCLC) accounts for about 13% of lung cancers. With a decreasing incidence in the last twenty years, SCLC remains a cancer with a dismal prognosis due in particular to a short doubling time which explains the metastatic presentation in nearly two thirds of the cases at diagnosis. This disease has a particular propensity to recur locally and disseminate in the brain. Hence, there have been several randomized trials assessing the role of thoracic and brain radiotherapy. Two individual data-based meta-analyses showed that thoracic radiotherapy and prophylactic cranial irradiation (PCI) should be part of the therapeutic strategy. Although platinum based chemotherapy combined to etoposide remains the cornerstone of SCLC treatment, since the 1980s radiotherapy has taken a growing place in multidisciplinary care. The treatment of stages I to III, is based on concomitant chemoradiation in fit patients and prophylactic cranial irradiation at the dose of 25 Gy in 10 fractions. Recent studies have confirmed that concomitant hyperfractionated accelerated radiotherapy at the dose of 45 Gy in 30 twice daily fractions, in 3 weeks gives the best results. However for patients who cannot receive HFART, once daily radiotherapy at the dose of 66 Gy in 33 fractions, may be an alternative. Five-year survival in the latest randomized studies is around 30-35% in SCLC patients having received concomitant CTRT and prophylactic cranial irradiation. Radiotherapy has also a place in metastatic SCLC. The pivotal treatment is of course systemic treatment with platinum based chemotherapy and Etoposide. There is however randomized evidence that consolidation thoracic radiotherapy at the dose of 30 Gy in 10 fractions, administered to responders may improve the outcome of patients with extensive disease. A randomized phase II trial has also tried to evaluate the role of consolidation radiotherapy, not only to intra-thoracic disease, but also to extracranial metastases in ED SCLC. The results were encouraging. Prophylactic cerebral irradiation (PCI) remains a standard of care in non metastatic disease in good responders but its place is more controversial in the metastatic setting. Most advances in SCLC management are based on a better integration of radiotherapy and chemotherapy, even in extensive disease. Teaching Lecture: Update on the management of SCLC

Teaching Lecture: How to combine checkpoint inhibitors with radiotherapy?

SP-0215 How to combine checkpoint inhibitors with radiotherapy? K. Harrington 1 1 The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Division of Radiotherapy and Imaging, Sutton, United Kingdom Abstract text There is enormous excitement about the potential for combining radiotherapy with immune checkpoint inhibitors as a means of enhancing outcomes for patients with a variety of cancers. In recent years, we have begun to understand in great detail the biological effects of radiation on tumour (and normal) cells and this knowledge has informed our thinking on how we might best exploit radiation-induced immunogenic cell death for patient benefit. In particular, we have a much clearer perspective on the importance of molecular responses to DNA damage and their interactions with immune sensing mechanisms in the cell. In this presentation, the interplay between DNA damage and nucleic acid sensors will be reviewed, with specific focus on the cGAS/STING axis. However, other innate immune effectors such as toll-like receptors, RIG-I and mda5 will also be discussed. In addition, opportunities for combination therapies will be discussed in the context of neoadjuvant, concomitant and adjuvant use of immune checkpoint inhibitors, encompassing the PD-1/PD-L1 axis but also considering other more novel agents. The importance of the fractional and total dose of radiation will also be discussed with a view to interpreting existing clinical trial data and informing future trial design. Finally, the current and potential future roles for both predictive and prognostic biomarkers will be evaluated. Teaching Lecture: How does brachytherapy fit in the modern management of penile cancer? SP-0216 How does brachytherapy fit in the modern management of penile cancer? J. Crook 1 1 BC Cancer Agency - Southern Interior, Radiation Oncology, Kelowna, Canada Abstract text Penile cancer is uncommon in western society, accounting for fewer than 1% of malignancies in men. When detected early, it is curable and penile conserving modalities should be considered first and foremost. If neglected and associated with spread to regional nodes, 5-year survival is reduced to 20-50% for inguinal node involvement and 10% when pelvic nodes are involved.The majority of penile cancers are of squamous cell (SCC) origin, and as such are both radiosensitive and radiocurable. About 50% are associated with HPV and as is the case for HPV-induced squamous cancer at other sites, may be more responsive to chemo-radiotherapy. For SCC localized to the glans, brachytherapy is a convenient and effective means of delivering radiotherapy. There is abundant experience over several decades using low dose rate brachytherapy (LDR) employing temporary implantation of iridium-192 wire, or more recently using Pulse Dose Rate afterloading with a high intensity Ir-192 stepping source and hourly fractions that mimic LDR radiobiology. Penile preservation rates are about 85% at 5 years and 70% at 10 years. Ideal tumors are confined to the glans and < 4 cm in diameter. Higher grade is not a contraindication to brachytherapy but does determine nodal management. Surgical nodal staging is

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