ESTRO 2023 - Abstract Book

ESTRO 2023

Saturday 13 May

S1

Teaching Lecture: Health services research for trialists

SP-0001 Health services research for trialists K. Spencer United Kingdom

Abstract not available

Teaching Lecture: Radiation-induced tumour cell migration - Why does it matter and what can we do about it?

SP-0002 Radiation-induced tumour cell migration - Why does it matter and what can we do about it? J. Birch 1 1 University of Glasgow, School of Cancer Sciences, Glasgow, United Kingdom Abstract Text Radiotherapy (RT) is a highly effective and potentially curative treatment used in many solid cancers for local control and for palliative purposes. However, a body of research has emerged over the last few decades, across numerous cancer types that point to the potential for RT to promote metastatic spread. Numerous mechanisms have been implicated in this response including selective pressure on surviving cancer cells, increase of circulating tumour cells (CTCs), modulation of inflammatory and stress signalling, epithelial to mesenchymal transition, induction of actin-myosin contractility and promotion of an invasion-permissive tumour stroma. Despite the growing array of preclinical evidence, meaningful interrogation of the impact of RT on metastasis in the clinic is sparse, and the subject remains a contentious issue. The lack of clinical data to support RT induced metastasis potentially invokes a false sense of security- we don’t see it, so why does it matter? Of course gathering data to support or refute this view point is inherently difficult, considering the ubiquitous use of RT as standard of care in many cancers plus the different delivery modalities and varying treatment protocols used. This lecture will explore the biology behind the pro-metastatic effects of RT, whether the weight of pre-clinical evidence is enough to indicate clinical relevance, and finally the potential new therapeutic window that it presents. SP-0003 Total neoadjuvant therapy in rectal cancer: When, why, how C. Marijnen 1 1 Netherlands Cancer Institute and Leiden University Medical Center, Radiation Oncology, Amsterdam and Leiden, The Netherlands Abstract Text Until recently, the standard of care for locally advanced rectal cancer (LARC) consisted of neoadjuvant chemoradiotherapy, followed by surgery according to the total mesorectal excision principles. This strategy has decreased the rates of local recurrences below 10% at 5 years. To improve quality of life, interest in organ preservation has increased, even in patients with locally advanced disease. Unfortunately, distant recurrences still remain a problem, with 5-year disease free survival rates of about 65% for locally advanced rectal cancer patients. The beneficial effect of postoperative adjuvant chemotherapy in rectal cancer is limited, especially after neoadjuvant (chemo)radiotherapy (CRT). One possible explanation is the poor compliance to chemotherapy after major surgery. In addition, the long interval between diagnosis and start of postoperative chemotherapy may facilitate outgrowth of micrometastases. Introducing chemotherapy before surgery, may therefore improve compliance and efficacy. Chemotherapy in a total neoadjuvant treatment (TNT) regimen can be given either as induction or as consolidation chemotherapy. In the last decade, several large, randomized trials have been performed in order to prove the beneficial effect of TNT. The Polish, STELLAR and RAPIDO trial evaluated regimens with short course RT (5x5 Gy) combined with consolidation chemotherapy and compared this with standard CRT with or without adjuvant chemotherapy1–3. In contrast, the PRODIGE 23 trial compared CRT combined with consolidation chemotherapy with standard CRT followed by adjuvant chemotherapy 4. Furthermore, the CAO/ARO/AIO-12 and OPRA study evaluated the difference between induction and consolidation chemotherapy in combination with CRT5,6. In general, it can be concluded that TNT appears to improve disease free survival (DFS) in some studies (RAPIDO, PRODIGE 23), but not in others (STELLAR, Polish study) when compared to standard CRT. Overall survival (OS) benefit was not seen in any of these studies. The comparison between induction and consolidation chemotherapy did not reveal a difference in DFS or OS. However, all studies comparing TNT with standard chemoradiotherapy demonstrated a significant increase in the number of patients that achieved a pathological complete response (pCR). This was confirmed in a recent meta-analysis7 and may open a window of opportunity for organ preservation in this locally advanced patient group. Additionally, consolidation chemotherapy after CRT seems more effective in achieving a pCR than induction chemotherapy before CRT. Despite these results, the optimal treatment strategy is still not clear. All above mentioned trials used different chemotherapy regimens, with variation in the number of courses as well as in the choice for doublet or triplet therapy. Also, the interval from start of treatment to evaluation varied in the different trials, hampering a firm conclusion about the best strategy. Given that no improvement in overall survival is observed in any of the trials, one has to be cautious about the increase in toxicity that is unavoidable with intensified treatment. The optimal neoadjuvant chemotherapy should therefore be balanced between efficacy and toxicity. Adequate patient selection is a prerequisite in this neoadjuvant setting to avoid unneccessary overtreatment and toxicity. Further insight in optimal strategy, patient selection and toxicity profiles will be provided during this talk. Teaching Lecture: Total neoadjuvant therapy in rectal cancer: When, why, how