ESTRO 2023 - Abstract Book

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ESTRO 2023

genes and then with processes and found, that processes which differentiate BCS and IORT exosomes are: Wnt signaling pathway, cell migration, TGF β receptor signaling pathway, cell-cell adhesion, and cell cycle arrest. Conclusion This is the first report documenting the miRNA cargo of exosomes in surgical wound fluids in BCS and IORT patients. This comprehensive approach which allows for a deeper and broader analysis of miRNA cargo of EXO-SWF enables a better understanding of their molecular and functional significance. Moreover, the presented results may be a starting point for modifying the treatment scheme by targeting specific molecules and signaling pathways.

PO-2211 Early data of a phase II study of PRaG3.0 regimen for remedy of HER2-expressing advanced pan-cancer

M. Xu 1 , R. Chen 1 , Y. Kong 1 , X. Zhao 1 , L. Zhang 1

1 Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China, Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China, Suzhou, China Purpose or Objective With the advancement of molecular detection and tumor microenvironment researches, the progress of anticancer therapy tends to focusing on pan-cancer analysis, targeted therapy and immunotherapy. Evidences have shown that radiotherapy can induce a systemic anti-tumor immune response, which may potentially sensitize PD-1/PD-L1 inhibitors. Previous phase II trial showed that radiotherapy combined with PD-1 inhibitor and GM-CSF (PRaG regimen) has obtained promising results. Meanwhile, HER2 is expressed in a variety of solid tumours. Preclinical studies indicated that a novel HER2-targeting antibody-drug conjugate (RC-48 ADC) elicit immunogenic cell death and selectively radiosensitize to tumours. An exploratory phase II trial was conducted to assess the initial clinical efficacy and safety of PRaG3.0 regimen （ RC48-ADC combined with radiotherapy, PD- 1/PD-L1 inhibitor sequential GM-CSF and IL-2 ） for treatment of HER2-expressing pan- cancer. Materials and Methods Patients with advanced, confirmed HER2-expressing(IHC3+, 2+ or 1+) solid tumors that had progressed after the standard of care or intolerance were enrolled. In the cycle, those received RC48-ADC(2.0 mg/kg d1), then stereotactic body radiation therapy or hypofractionated radiotherapy(2-3 doses of 5-8Gy) was delivered for one metastatic lesion every other day, followed by GM-CSF(200µg d3-7), sequential IL-2(2million IU d8-12), and PD-1/PD-L1 inhibitor was dosing within one week after completion of radiotherapy. PRaG3.0 regimen was repeated every 3 weeks for at least 2 cycles. After RC48-ADC combined with PD-1/PD-L1 inhibitor sequential GM-CSF and IL-2 for at least 6 cycles, then maintenance with PD-1/PD-L1 inhibitor was administered until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). This trial is registered with ClinicalTrials.gov, No. NCT05115500. Results By September 2022, a total of 26 patients were enrolled , involved stomach cancer, pancreatic cancer, colon cancer, cervical cancer, ovarian cancer, lung cancer, prostate cancer, renal pelvic cancer, breast cancer and rectum cancer. 20 patients underwent first time assessment. The ORR was 45%, disease control rate was 75% and the median PFS was 5.5 months(95%CI, 4.4-6.6 months) at the time of evaluation. The common treatment related adverse events were alopecia (84.6%), fatigue (69.2%), fever(38.5%), hepatic damage(7.7%), nausea(30.8%), rash69.2%), thyroid dysfunction(11.5%). One patient occurred grade 3 hepatic damage. Conclusion The PRaG3.0 regimen is well tolerated with acceptable toxicity. Our data suggest the PRaG3.0 regimen further improve the synergistic antitumor effects, this precise paradigm may provide a promising salvage treatment of HER2-expressing advanced solid tumors. 1 Radboud University Medical Center, Radiation Oncology, Nijmegen, The Netherlands; 2 Radboud University Medical Center, Medical Imaging, Nijmegen, The Netherlands Purpose or Objective Limited diffusion of oxygen into distant areas in combination with an increased oxygen consumption rate (OCR) leads to hypoxia in most solid tumors. Hypoxic areas in tumors are known to be radioresistant and can have a negative effect on the anti-tumor immune response. Recently, it became clear that tumor cells are also reliant on oxidative phosphorylation (OXPHOS) for their energy, opposing the longstanding notion that tumor cells primarily rely on glycolysis under aerobic conditions. Therefore, we aim to alleviate hypoxia through metabolic reprogramming by inhibition of the oxidative metabolism to sensitize tumor cells for radiotherapy, immunotherapy and its combination. Materials and Methods Murine mouse colon MC38 cells containing a hypoxia response element upregulating eGFP under hypoxic conditions, were used to grow spheroids. 24h after spheroid formation, the spheroids were treated with different concentrations of the OXPHOS inhibitors IACS-010759, atovaquone and metformin. The eGFP signal for hypoxia was followed over time using the Incucyte Zoom Live Cell Imaging system. The hypoxic area and total spheroid are was determined and used to quantify the fraction of hypoxia. PO-2212 Metabolic reprogramming using OXPHOS inhibitors alleviates hypoxia in tumor spheroids A. Beerkens 1,2 , D. Boreel 1,2 , F. Göllesch 1 , P. Roelofs 1 , S. Heskamp 2 , G. Adema 1 , P. Span 1 , J. Bussink 1

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