ESTRO 2021 Abstract Book

S552

ESTRO 2021

SP-0708 What radiotherapy dose do we need to achieve clinical complete response in early and advanced tumours? A. Appelt 1 1 University of Leeds, Leeds Institute of Medical Research at St James's, Leeds, United Kingdom Abstract Text Radiotherapy for rectal cancer has traditionally been used in the (neo-)adjuvant setting, where its key function has been to control subclinical disease not managed by the primary surgery. The increased focus on organ preservation raises the evident question: Are the pre-operative radiation dose-fractionation schedules also optimal for dedicated non-surgical management? In particular, are there some patient groups where higher tumour doses might be preferable, in order to achieve clinical complete response (and long-term control) with (chemo-)radiotherapy alone? This talk will initially briefly summarize the trials which have examined the dose-response question for rectal cancer, overwhelmingly in the neoadjuvant setting. This directly leads to a discussion of tumour response as an endpoint, and how pathological response measures – pathological complete response (pCR), tumour regression grade (TRG) – differs from those used in the organ preservation setting (e.g. clinical complete response (cCR) and long-term organ preservation). The bulk of the presentation will focus on the (limited) clinical evidence for benefits of dose-escalation for non-surgical management, including an attempt to estimate a dose-response relationship for local control based on the existing – primarily retrospective – literature. The impact of tumour staging, volume and other disease factors on cCR and long-term control will be discussed. Finally, the risk of toxicity with dose-escalation should not be ignored: Normal tissue complication probability has scarcely been studied in the organ preservation setting. Even if patients may expect increased tumour control (and thus increased organ preservation) with a higher dose, the risk of radiation-induced toxicity may offset that in the overall risk-benefit estimate. SP-0709 Radiosensitisation and systemic treatment to increase clinical complete response E. Fokas 1 1 University of Frankfurt, Department of Radiotherapy and Oncology, Frankfurt, Germany Abstract Text Preoperative 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) to patients with clinically staged TNM stage II/III rectal cancer has resulted in excellent local control. However, as the management of rectal cancer is shifting to organ preservation, various strategies have been explored to enhance clinical complete response. Here, the evidence on radiosensitizing molecular agents and intensified concomitant chemotherapy to achieve complete response and improve clinical outcome will be discussed. Abstract Text Until recently, the standard of care for locally advanced rectal cancer (LARC) consisted of neoadjuvant (CRT), followed by surgery according to the TME principles. This strategy has decreased the rates of local recurrences below 10% at 5 years. However, distant recurrences remain a problem for these patients. The beneficial effect of postoperative adjuvant chemotherapy in locally advanced rectal cancer is limited. One possible explanation is the pore compliance to chemotherapy after major surgery. Introducing chemotherapy earlier in the treatment by giving it neoadjuvantly, may improve compliance and efficacy. In the last few years, numerous phase I and II studies have been performed in order to find the optimal timing: starting with chemotherapy or with the (chemo)radiotherapy? Also, the optimal radiotherapy schedule has yet to be defined. The recently published randomized phase III RAPIDO trial, comparing hypofractionated 5x5 Gy schedule followed by neoadjuvant CAPOX (x6), with standard chemoradiotherapy, demonstrates at 3 years a reduction of disease related treatment failures in the experimental arm from 30.4% to 23.7%. In addition, an increase in complete pathological responses from 14% to 28% was observed. The randomized phase III Prodige-23 trial, comparing neoadjuvant FOLFIRINOX (x6) followed by chemoradiotherapy with chemoradiotherapy and postoperative FOLFOX (x12) demonstrated an increase in 3 years disease free survival from 68.5% to 75.7% in favor of the experimental arm. These results suggest that total neoadjuvant treatment is the preferred treatment strategy in LARC patients. However, all (neo)adjuvant treatment is accompanied by an increase in toxicity. Neoadjuvant strategies run a risk of overtreatment with unnecessary extra toxicity. Further insight in optimal strategy, patient selection and toxicity profiles will be provided during this talk. SP-0710 Clinical experiences on total neoadjuvant therapy in rectal cancer C. Marijnen 1 1 Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands

SP-0711 Personalised approaches towards organ preservation - Where are we now? M. Gambacorta Italy

Abstract not received

Symposium: Proving the clinical benefit of 15 years of IGRT

SP-0712 Heart sparing for lung radiotherapy E. Vasquez Osorio