ESTRO 38 Abstract book

S7 ESTRO 38

improvement is likely to occur with integration of novel immunotherapy agents, including multiple checkpoint inhibitors, personalised cancer vaccines, and other immune response modifiers. Tissue and blood-based biomarker data are needed to better understand how to personalise consolidation therapies most effectively. SP-0019 Active management of patient’s comorbidities (including respiratory and cardiac comorbidities) V. Westeel 1 1 Hôpital Univ. Jean Minjoz, Chest Disease Department, Besançon, France Abstract text The prevalence of comorbidity is high in lung cancer patients, up to 50 % in non-surgically treated patients. Pathologies, which share the same risk factor, smoking exposure, and diseases at increased risk after 70 years are particularly frequent in patients diagnosed with lung cancer. Chronic inflammation is also considered to contribute to lung cancer carcinogenesis in several comorbidities, such as COPD and cardiovascular diseases (CVDs). Because standard therapy includes chemotherapy, radiotherapy and immunotherapy in PD-L1≥1% NSCLC, many comorbidities can interfere with treatment decision. Pulmonary comorbidity Several lung diseases are associated with an increased risk of lung cancer. COPD is reported in approximately 50% of patients with NSCLC, including patients treated with chemo-radiotherapy. COPD is a risk factor for lung cancer, independent of smoking history, with COPD smokers five times more likely to develop lung cancer than smokers without COPD. Bronchiectasis has also been reported as an independent risk factor of lung cancer, because of recurrent microbial infections. Diagnosis of obstructive bronchial disease relies on spirometry to measure the FEV1 and the diffusing capacity for carbon monoxide. Therapeutic management can include smoking cessation, pharmacologic treatments, oxygen therapy and noninvasive ventilation, and early treatment and prevention of exacerbations (influenza and pneumococcal vaccination) and pulmonary rehabilitation (www.goldcopd.org). Several studies suggest an association between interstitial lung diseases (ILDs), particularly pulmonary fibrosis, and lung cancer. Treatment-related mortality and the risk of radiation pneumonitis are high in patients with ILD. Therefore, the diagnosis should not be ignored and the benefit of radiotherapy carefully considered, taking into account this high risk of toxicity and patient prognosis. Cardiovascular diseases Cardiovascular diseases (CVDs) are observed in approximately 25% of patients and represent the first cause of non-cancer death, in locally advanced NSCLC. Heart failure and cardiac arrhythmia are predictive of cardiac complications after chemo-radiotherapy. Heart failure, myocardial infarction and cardiac arrhythmias are associated with decreased survival rates in patients treated with chemoradiation for stage III NSCLC, while hyperlipidaemia might have a protective effect. Beside diagnosis and optimal treatment of CVDs, treatment adaptations may be necessary. Cisplatin, which requires large hydration cannot be used in patients with pre- Chronic renal disease is common in patients with lung cancer and impacts both systemic treatment and survival. The choice of the chemotherapy regimen and dose calculation should be adapted according to the glomerular filtration rate, using carboplatin rather than cisplatin, avoiding pemetrexed…(1) Infections, especially hepatitis B and HIV infection need to be diagnosed before treatment for stage III NSCLC. Cytotoxic chemotherapy can be responsible for HBV existing reduced LVEF. Other comorbidities

malignancy and therapy response, in order to effectively harness their anti-cancer potential. This is particularly relevant to late-stage and recurrent disease which are refractory to standard of care treatment, do not respond to targeted or T cell immunotherapy and that are consequently fatal. Glioblastoma (GBM) is such a cancer type, and the most malignant form of primary brain tumor in the central nervous system. Despite aggressive standard of care treatment, the median survival of GBM patients does not exceed 15 months. Tumor-associated macrophages/microglia (TAMs) are the most abundant non-cancerous cell types in human and murine GBM. Using murine models of GBM in which we examined the relative contribution of TAM, we found that radiotherapy alters infiltrating bone marrow-derived macrophages (BMDM) and brain-resident microglia (MG) content and phenotype.These cells undergo profound proteomic and transcriptional changes in the treated GBM tumor immune microenvironment, and support radiotherapy resistance and relapse. We demonstrated that the convergence of MG and BMDM phenotype at recurrence relies on acquisition of neurodegenerating signals within the TIME, with activation of the Notch and TGFb pathways at its core. Limiting the acquisition of this recurrent signature in both BMDM and MG led to enhanced radiotherapy response and delayed recurrence in multiple GBM murine models. We propose that dampening thedynamics of macrophage subpopulation phenotype in GBM post treatment may be a fundamental step to take in combinatorial therapy. SP-0018 Optimal management of patients with unresectable stage III NSCLC: areas of controversy and ongoing research R. Dziadziuszko 1 1 Medical University of Gdansk, Dept. of Oncology and Radiotherapy, Gdansk, Poland Abstract text Results of definitive treatment of patients with unresectable stage III NSCLC have changed favourably over the last decade. With more precise imaging, invasive staging, 4D-CT treatment planing, and image-guided treatment delivery, concurrent radiochemotherapy protocols lead to median survival of approximately 24 – 30 months and 5-year survival probability of approximately 30 - 35%. These indices are further improved with integration of consolidation immunotherapy as demonstrated in the PACIFIC trial with PDL1 inhibitor durvalumab. Further progress in this field is likely to result from improvements in both local and systemic therapies. Old dose/volume/fractionation reserach questions need still to be re-evaluated from the perspective of optimisation of local control versus toxicities. Most effective hypofractionation protocols and perhaps different radiotherapy doses to primary tumour and mediastinal lymph nodes are the key reserach questions. More research focus on late toxicity, particularly cardiac and pulmonary, is needed as our patients live longer and are more likely to experience this toxicity. Systemic research trials are designed to test the use of different immune checkpoint inhibitors as consolidation treatment with concurrent, sequential or even exclusive radiotherapy in properly selected patient subsets. Further Symposium: Optimal management of patients with unresectable stage 3 NSCLC SP-0017 Standard of care in 2019 F.McDonald 1 1 Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Department of Radiotherapy, Sutton, United Kingdom Abstract not received