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e14609 Background: Radiotherapy (RT) can prime an anti-tumor immune response. Unfortunately, this response rarely generates total tumor destruction and abscopal effect. When activated by RT, intratumorally (IT) administered hafnium oxide nanoparticles (NBTXR3) locally increase radiation dose deposit and tumor cell death compared to RT alone. We hypothesized that NBTXR3 + RT could enhance the anti-tumor immune response, both in mice and humans. Methods: Murine CT26 cells were injected in both flanks of immunocompetent mice. When tumor volume reached 50-120mm3, NBTXR3 (or vehicle) was injected IT in right flank tumors only, then irradiated (3x4Gy). Mice were sacrificed when tumors reached 800mm3. Alternatively, tumors were collected 3 days after last RT fraction and immune cell infiltrates analyzed by immunohistochemistry (IHC). Patients (pts) with locally advanced Soft Tissue Sarcoma (STS) (NCT02379845) received NBTXR3 + RT or RT alone. Pre- and post-treatment (biopsy and resection, respectively) tumor tissues from pts were analyzed by IHC and Digital Pathology for immune biomarkers ( > 16 pts per arm). Results: In mice, IHC analyses showed an increase of CD8+ T cells infiltrates in both flanks of mice treated with NBTXR3+RT, while this was not observed in animals treated with RT alone. Furthermore, ICH analysis of post- vs pre-treatment samples from STS pts showed a marked increase of CD8+ and PD1 biomarkers for pts treated with NBTXR3 + RT, while no differences were seen for pts treated with RT alone. Conclusions: NBTXR3 + RT markedly changes the tumor immune profile in a similar manner in mice and pts with STS. We hypothesize that this adaptive immune response could help convert a local tumor microenvironment to a “hot” phenotype and thus improve the efficacy of immune checkpoint inhibitors. These results led us to investigate the safety and systemic effect of NBTXR3 activated by stereotactic ablative RT (SABR) in combination with anti-PD-1 antibody in pts with locoregionally recurrent or metastatic (to lung or liver) Head and Neck squamous cell carcinoma HNSCC, as well as in metastatic non-small cell lung cancer (NSCLC) and liver metastasis patients [NCT03589339].

e15149Background: Radiotherapy (RT) can prime an anti-tumor immune response. Unfortunately, this response is not sufficient to allow tumor destruction and abscopal effect (effect on a distant untre...

Purpose Well-differentiated metastatic endocrine carcinomas are difficult to manage because of variable disease outcome. New prognostic factors are required. These tumors overexpress somatostatin receptors (sst), implying the use of somatostatin analogs for tumor localization by somatostatin receptor scintigraphy using indium-111–pentetreotide (111In-pentetreotide) and for medical treatment. The aim of the present study was to evaluate the correlation between 111In-pentetreotide scintigraphy, sst receptor expression, and prognosis. Patients and Methods Between 1994 and 2002, 48 consecutive patients with well-differentiated endocrine carcinomas and a negative 111In-pentetreotide scintigraphy were retrospectively paired according to sex, age, and tumor localization with 50 patients with well-differentiated endocrine carcinomas and a positive tracer uptake at 111In-pentetreotide scintigraphy. Overall survival and expression of sst1 to sst5 receptors by immunohistochemistry were assessed. Results The lack of tracer uptake at the 111In-pentetreotide scintigraphy seemed to be a poor prognostic factor (P = .007) for overall survival by Kaplan-Meier test and in multivariate analysis; age and absence of clinical secretory syndrome also seemed to be poor prognostic factors. The tracer uptake (positive 111In-pentetreotide scintigraphy) correlated with the tumor expression of somatostatin receptor sst2 (P < .001) but not with that of sst1, sst3, sst4, or sst5. In a bivariate analysis, lack of sst2 expression also significantly correlated with poor prognosis. Conclusion We demonstrate the prognostic value of 111In-pentetreotide scintigraphy in well-differentiated malignant endocrine tumors. In these tumors, sst2 somatostatin receptor expression correlates with both tracer uptake and a better prognosis.

e14615 Background: NBTXR3 are functionalized hafnium oxide nanoparticles, undergoing seven clinical trials for enhancing radiation therapy (RT). The high electron density of the nanoparticles, when exposed to radiotherapy (NBTXR3 + RT), allow absorption/deposition of a high radiation dose within the cancer cells to physically kill the cells, and possibly improve outcome. Besides, NBTXR3 + RT has shown subsequent ability to enhance immunogenic cell death and immune response in preclinics. We hypothesized that NBTXR3 + RT could trigger an enhanced immune response when compared to RT in patients with STS. Methods: Tumor tissues pre- (biopsy) and/or post-treatment (resection) were collected from patients (pts) with locally advanced STS, who received either NBTXR3 as intratumor injection and RT (14 pts) or RT (12 pts), as preoperative treatment (NCT02379845). Immunohistochemistry and Digital Pathology for immune biomarkers and for Immunoscore (CD3/CD8) were analyzed. Gene expression profiling and pre-optimized immune-gene signatures called Immunosign were also used. Results: A significant increase of T cells (CD3+, CD8+) and a marked increase of CD103+ immune cell infiltration post- vs pre-treatment were observed for NBTXR3 + RT ( P< 0.01), while no differences were seen for RT. Post-treatment, an increased Immunoscore (CD3 + CD8 cell densities) was observed for NBTXR3 + RT compared to RT (P < 0.07). Consistently, the up-regulation of pan immune genes expression and specifically expression of adaptive immunity genes between pre- and post-treatment, was pronounced for NBTXR3 + RT when compared to RT. Functional analysis of genes up-regulated in NBTXR3 + RT showed an enrichment of cytokine activity (IL7, IFNA, IL16, IL11, IFNG), adaptive immunity (RAG1, GZMA, TAP1, TAP2, TBX21, STAT4, IFNG, LCK, LTK, CD37, CD22) and T cell receptor signaling pathway (CD28, CTLA4, CD274, BTLA, TIGIT, CD40LG, CD5, CD3E, ZAP70). Conclusions: NBTXR3 + RT induces a specific adaptive immune pattern. As such, it may contribute to convert “cold” tumor into “hot” tumor and be effectively combined with immunotherapeutic agents across oncology. These data warrant more tissue samples evaluation to reinforce these findings.

17008 Background: Head and neck squamous cell carcinoma (HNSCC) accounts for 95% of the tumors appearing in the upper aerodigestive tract. HNSCC represents about 10% of cancer in men and is the fourth most common cancer after prostate cancer, lung cancer and colorectal cancer. EGFR (epidermal growth factor receptor) is overexpresssed in 85 % of HNSCC and the inhibition of its kinase activity constitutes an important therapeutic strategy. Our work aims to study the action of an EGFR inhibitor (erlotinib) in patients with HNSCC; and to identify predictive markers of response in order to select patients that can benefit of the treatment. Methods: A pilot study has been conducted in HNSCC patients pending surgery were treated with neoadjuvant erlotinib. Tumor tissues biopsies were collected before and after treatment. Despite the short time of treatment (i.e. median time 20 days), twelve patients out of the 42 included in the study, experienced a clinical response (measured by 25% tumor shrinkage) while 28 we...

5513 Background: To date, neither immunohistochemistry (IHC) nor molecular analyses have identified prognostic markers of response to epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors in SCCHN. Thus, the selection of patients who could benefit from such agents remains a challenge. We designed a ‘pilot’ clinical trial of patients (pts) with SCCHN pending first-line surgery of their disease. Methods: Pts with resectable SCCHN received erlotinib at 150mg/day during the period between pan-endoscopy and surgery. Pharmacokinetic (PK) samples were collected during treatment, which ceased the day before surgery. Results: Thirty five pts were recruited. All of them had resectable SCCHN: oral cavity (17 pts), oropharyngeal (7 pts), hypopharyngeal (5 pts), larygeal (6 pts). Thirty pts received full treatment with erlotinib and the main reason for discontinuation was rash. The median duration of treatment was 21 days (14–27). All pts were evaluated clinically and their tumors assessed radiologically before and after treatment. Out of 30 evaluable pts, 8 were considered as good responders (30–80% decrease in tumor size), 18 had stable disease and 2 had minor progression. Expected toxicities were observed: rash (grade 2/3 in 11 pts), diarrhea (grade 2 in 1 pt). All pts underwent surgery. The incidence of post-operative complications was similar to our historical series. No mutations in the catalytic domain of EGFR TK were found. All tumors were positive for EGFR by IHC. Correlative statistical analyses between PK, toxicity and response data are ongoing and will be presented. Neither over expression of EGFR nor other IHC markers alone were found to be good predictive markers of efficacy. Retrospective analysis of morphological and IHC evaluation in some cell cycle regulators (mainly p21) appeared to be predictive of erlotinib efficacy (sensitivity 87.5%, specificity 88%). Conclusions: Neo-adjuvant treatment with erlotinib in SCCHN pts is well-tolerated. This trial demonstrated a useful prospective method to potentially aid patient selection to improve the design of post-operative adjuvant treatment combinations. No significant financial relationships to disclose.

9705 Background: IHC appears to be the required test for the selection of patients for a monoclonal antibody based targeted treatment with C225 (Erbitux). To validate the usefulness of IHC, confirm...