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Describes the stones used in the Assyrian sculptures. Inscriptions of Sennacherib; Type of limestone of special quality; Geological map of the Judi Dagh.

While neoadjuvant immunotherapy for melanoma has shown promising results, the data have been limited by a relatively short follow-up time, with most studies reporting 2-year outcomes. The goal of this study was to determine long-term outcomes for stage III/IV melanoma patients treated with neoadjuvant and adjuvant programmed cell death receptor 1 (PD-1) inhibition. This is a follow-up study of a previously published phase Ib clinical trial of 30 patients with resectable stage III/IV cutaneous melanoma who received one dose of 200 mg IV neoadjuvant pembrolizumab 3 weeks before surgical resection, followed by 1 year of adjuvant pembrolizumab. The primary outcomes were 5-year overall survival (OS), 5-year recurrence-free survival (RFS), and recurrence patterns. We report updated results at 5 years of follow-up with a median follow-up of 61.9 months. No deaths occurred in patients with a major pathological response (MPR, <10% viable tumor) or complete pathological response (pCR, no viable tumor) (n = 8), compared to a 5-year OS of 72.8% for the remainder of the cohort (P = 0.12). Two of eight patients with a pCR or MPR had a recurrence. Of the patients with >10% viable tumor remaining, 8 of 22 patients (36%) had a recurrence. Additionally, the median time to recurrence was 3.9 years for patients with ≤10% viable tumor and 0.6 years for patients with >10% viable tumor (P = 0.044). The 5-year results from this trial represent the longest follow-up of a single-agent neoadjuvant PD-1 trial to date. Response to neoadjuvant therapy continues to be an important prognosticator with regard to OS and RFS. Additionally, recurrences in patients with pCR occur later and are salvageable, with a 5-year OS of 100%. These results demonstrate the long-term efficacy of single-agent neoadjuvant/adjuvant PD-1 blockade in patients with a pCR and the importance of long-term follow-up for these patients. Clinicaltrials.gov , NCT02434354 • This represents the longest follow-up of a neoadjuvant trial of single-agent PD-1 blockade for cutaneous melanoma to date. • Pathologic response to treatment remains prognostic, as patients with ≤10% viable tumor remaining had a 5-year OS of 100%. • Patients with ≤10% viable tumor who had a recurrence do so after 3 years of follow-up and have salvageable recurrences. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Many patients treated with anti-PD-1 therapy do not show a clinical response. Preclinical studies suggest that adding hypofractionated radiotherapy (HFRT) to anti-PD1 can increase the efficacy of immunotherapy through several mechanisms including increased antigen presentation. We conducted a prospective trial testing the combination of pembrolizumab and HFRT in patients with metastatic solid tumors.Materials/methods: This prospective single-institution phase I trial tested pembrolizumab in combination with HFRT in patients with metastatic cancers (NSCLC, melanoma, pancreas, breast, others) and an ECOG performance status of 0-1. Melanoma and NSCLC patients were required to have progression of disease on anti-PD1, having received ≥ 2 doses of anti-PD1 and progression documented by RECIST v1.1. Patients were required to have an index lesion ≥1 cm that was amenable to HFRT and at least one other lesion that was not irradiated and could be followed for response using RECIST criteria. Pembrolizumab 200 mg IV every 3 weeks was administered beginning 1 week prior to the first fraction of radiation. The HFRT dose was 8 Gy x 3 fractions or 17 Gy x 1 fraction, determined by randomization during the Expansion phase. The primary objective was the safety of HFRT combined with pembrolizumab, with dose-limiting toxicity (DLT) defined as Grade ≥ 3 non-hematological toxicity related to the combination of Pembrolizumab and HFRT. The secondary objective was the radiographic response of metastatic lesions outside the radiation field as measured by RECIST.Results: A total of 59 patients aged 27-90 years (median 60) were enrolled from March 2015 to December 2018 (24 in the Safety Phase and 35 in Expansion Phase). 40 patients (67.7%) had treatment-related AEs, of which 4 were grade 3 and none were grade 4. One patient experienced hepatitis, classified as DLT. While most patients did not have a radiologic response, in patients with metastatic melanoma, 7 of 16 (43.8%, exact 95% CI 19.8-70.1%) had an objective response of non-irradiated lesions to HFRT + pembrolizumab, including 3 complete and 4 partial responses. Responses are durable with 3/3 complete responders alive with no progression, and 3/4 partial responders alive with 2 having no evidence of progression. Among melanoma patients, only 2 of 7 (29%) responders received ipilimumab prior to enrollment, compared to 8 of 9 (89%) non-responders (P = 0.035). An increase in Ki67+ PD-1+ non-naïve CD8 T-cells was observed in the blood 2 weeks after HFRT, but the magnitude did not correlate with likelihood of response. Responses were observed after either 17 Gy x 1 fraction or 8 Gy x 3 fractions, with no difference in response rate by fractionation.Conclusion: This study suggests that HFRT administered with concurrent pembrolizumab is associated with acceptable toxicity and that in patients with metastatic melanoma progressing on anti-PD-1 therapy, this approach yields an ORR of 44%. [ABSTRACT FROM AUTHOR]