ESTRO 38 Abstract book

S171 ESTRO 38

increase the prevalence of bacteria linked to anticancer immunosurveillance and adapt bacteria ecosystem accordingly. SP-0334 The Microbiome and treatment side-effects Y. Touchefeu 1 1 Institut des Maladies de l'Appareil Digestif- University Hospital- Nantes- France, Hepato-Gastroenterology, Nantes, France Abstract text Radiation therapy and chemotherapy induce major changes in the composition of the gut microbiota. Basic and clinical data suggest that the intestinal microbiota may play an important role in the pathogenesis of chemo- or radiation-induced mucositis. Further metagenomic studies, investigating microbiota gene functions, are required to better understand the impact of microbiota disruption during cancer treatments. Strategies can be developed to prevent or treat potentially life threatening treatment complications, using manipulations of the intestinal microbiota. Probiotics may be beneficial to prevent chemo or radiation-induced diarrhoea. Gut microbiota identification could also be used as a predictive marker for radiation and chemotherapy adverse effects such as mucositis, diarrhoea, fatigue, pain and bacteremia, and could guide preventive strategies. Abstract text Background: Salivary gland hypofunction and xerostomia are major complications to head and neck radiotherapy. We have conducted a trial assessing the safety and efficacy of adipose tissue-derived mesenchymal stem cell (ASC) therapy for radiation-induced xerostomia. Patient and Methods: A randomized, placebo-controlled phase I/II trial included 30 patients, randomized in a 1:1 ratio to receive ultrasound-guided transplantation of ASCs or placebo to the submandibular glands. Patients had previously received radiotherapy for a T1-2, N0-2A, human papillomavirus-positive, oropharyngeal squamous cell carcinoma. The primary outcome was the change in unstimulated whole salivary flow rate, measured before and four months after the intervention Results: No severe adverse events were detected. Unstimulated whole salivary flow rates significantly increased in the ASC-arm at one (33%; p=0.048) and four months (50%; p=0.003), but not in the placebo-arm (p=0.6 and p=0.8), compared to baseline. The ASC-arm symptom scores significantly decreased on the xerostomia and VAS questionnaires, in the domains of thirst (-22%, p=0.035) and difficulties in eating solid foods (-2%, p=0.008) after four months compared to baseline. The ASC-arm showed significantly improved salivary gland functions of inorganic element secretion and absorption, at baseline and four months, compared to the placebo-arm. Core-needle biopsies showed increases in serous gland tissue and decreases in adipose and connective tissues in the ASC-arm compared to the placebo-arm (p=0.04 and p=0.02, respectively). MRIs showed no significant differences between groups in gland size or intensity (p < 0.05). In addition, outcome from one-year follow-up study along with next the stem cell studies in the pipeline will be presented. Conclusions: We have conducted the first-in-man transplantation of Symposium: Reducing the normal tissue effects of RT SP-0335 Stem cell replacement to overcome RT induced xerostomia C. Von Buchwald 1 , C. Groenhoej 1 , C.D. Lynggaard 1 1 Rigshospitalet- Copenhagen- Denmark, Department of Orl- H and N Surgery And Audology, Copenhagen, Denmark

SP-0332 The Microbiome & Cancer Therapies V. Pazienza 1 1 Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, Gastroenterology, San Giovanni Rotondo, Italy Abstract text Despite continuous advances in cancer related therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. Cancer is a major health burden worldwide being among the top two killing disease in the frame of non comunicable diseases that are responsible of the 70% of deaths worldwide. There is a growing evidence that gut bacteria can affect the response to chemo, immuno and radiotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. In this lecture is presented the existing knowledge concerning the role of the microbiota in mediating chemo, immuno and radiotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments. Abstract text The microbiome is associated with immunity and the development of a healthy immune system. Several factors are known to influence the variable part of the microbiome such as host lifestyle, environment, diet, genotype, pathobiology, inflammation etc.. Parameters associated with a healthy and fit microbioma are essentially the high diversity and a resilient feauture i.e the capacity to cope with a physiological stress. An umbalanced scenario together with a concomitant factors such as an inflammation process and/or presence of pathogens can cause complex diseases. It was not then surprising the finding that outcome of immunotherapeutic strategies in cancer patients can be dependent on the gut microbiome. Treatment of cancer with check point inhibitors capable to unleash T cells to expand exponentially and kill transformed cells, is the newest and best treatment strategy being developed in the last decade. A true revolution in oncology is ongoing and we are seeing dramatic responses and long term overall survival in critical deadly tumors like advanced melanoma, non-small cell lung cancers, renal cell carcinomas. Not all patients respond and some of them show severe autoimmune toxicities. Data are now emerging suggesting that response to ICI therapy, particularly anti-CTLA4, is associated to microbioma composition and that restored immunity and antitumor activity of ICI could be achieved only with transplantation of stool samples from responder patients. Immunological mechanisms underlying these findings are still in the process of being fully elucidated. Significance of these findings is quite relevant for future strategies in oncology. We are today facing the possibility that modulation of microbioma with probiotics or fecal transplants can SP-0333 Immune effects of the microbiome on cancer treatment M. Nuti 1 1 Sapienza University of Rome, Division of Medical Oncology B- Department of Radiological- Oncological and Pathological Sciences- Policlinico Umberto I, Rome, Italy