ESTRO 2021 Abstract Book

S671

ESTRO 2021

metastatic spread capacity in PCa. Materials and Methods

Liquid-biopsy-based markers such as CTCs and soluble factors were analyzed in the blood of castration- resistant PCa patients (CRPC) under androgen deprivation and aRT (n=28) at several time points during therapy. CTCs and immune cells were analyzed with multicolor flow cytometry and soluble factors with multiplex cytokine array and ELISA. The role of the chemokine receptor CXCR4 and the chemokine CCL-2 for stemness and RR was functionally analyzed in vitro , in vivo and in primary cultures using genetic and chemical targeting. Additionally, the influence of the bone environment on RR and stemness of PCa cells was investigated in the metastatic cultures on bone-peptides matrices by colony formation assay and γH2AX assay. Results We found that the degree of heterogeneity within the CTC population decreases during treatment, while EpCAM + CXCR4 + and panCK + CXCR4 + CTC populations are detectable without changes throughout and after aRT. These CTC subpopulations positively correlate with patients progression prior aRT and are associated with the occurrence of bone and lymph node metastases identified prior aRT. Interestingly, the CCL-2 plasma level correlates positively to patients progression and the occurrence of proinflammatory monocytes. In silico analyzes validated the strong correlation of CXCR4 with CCL-2 and its association with immune crosstalk and metastatic signatures. Clinical findings were functionally addressed in regards to potential association with RR in vitro in PCa cell lines including parental and radioresistant sublines of DU145 and LNCaP, and bone- tropic C4-2B and PC-3. We found CXCR4 and CCL-2 significantly enriched in cells with intrinsic and acquired radioresistance. Moreover, genetic and chemical targeting of CXCR4 and CCL-2 increased the radiosensitivity of PCa cells in vitro and in vivo . We found that the bone peptide osteocalcin enhances clonogenic survival after irradiation. Conclusion In summary, besides CTC count certain CTC populations may have the potential to identify PCa patients with bone metastasis and those who either do not respond to metastasis-directed aRT or have metastases outside the target volume of aRT. Further investigations are needed to address whether detailed CTC analysis may indicate patients benefiting from aRT to oligometastases. Moreover, this non-invasive dynamic method may allow for monitoring of therapy response and detection of disease progression at early stages. PD-0836 Watch-and-wait strategy : Where is a limit? Results from the pooled two prospective studies L. Pietrzak 1 1 Maria Sklodowska-Curie National Research Institute of Oncology, Radiotherapy, Warsaw, Poland Purpose or Objective Frequency and predictive factors for clinical complete response (cCR) in unselected patients are not well known. Materials and Methods Two prospective observational studies were designed and pooled to explore predictive factors for cCR. Both studies evaluated watch-and-wait strategy (w&w) in consecutive patients; the first single-institutional study in elderly with the small tumour, the second multi-institutional study in all the patients after standard of care preoperative radiotherapy. Results In total, 490 patients were analysed of whom 73 had cCR and 71 underwent w&w with the median follow-up of 24 months. Short-course radiotherapy alone, with consolidation chemotherapy and chemoradiation was given to 40.6%, 40.2% and 19.2% of the patients, respectively. Median interval to the first tumour response assessment was 10.5 weeks from the radiation start. cCR rates for cT1-2N0, intermediate risk (cT3 with unthreatened mesorectal fascia [MRF-] or cT2N+) and high risk cancers (cT4 or MRF+) were 39.0%, 16.8% and 5.4%, respectively. In multivariable analysis tumour volume (or alternatively tumour length and percentage of circumferential extension) and cN status were significant predictors for cCR. In circular cancers or with length ≥7 cm (n=184) cCR rate was 2.7%, sustained cCR 1.6% and the sensitivity of cCR diagnosis 23.1% (using a sum of sustained cCR and pathological complete response in persistent tumours as reference). None of 27 patients with the tumour volume larger than 120 cm 3 achieved cCR – see figure. Poster discussions: Poster discussion 19: Lower GI (colon, rectum, anus)