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Metastatic uveal melanoma (mUM) is a rare type of melanoma with poor outcomes. The first systemic treatment to significantly prolong overall survival (OS) in patients with mUM was tebentafusp, a bispecific protein that can redirect T-cells to gp-100 positive cells. However, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) may underestimate the clinical impact of tebentafusp. As metabolic response assessed by PET Response Criteria in Solid Tumors (PERCIST) has been reported to better correlate with clinical outcome, we here compared the patterns of radiological and morphological responses in HLA-A*02:01-positive patients with mUM treated with tebentafusp. In the 19 enrolled patients, RECIST showed an overall response rate (ORR) of 10%, median progression-free survival of 2.8 months (95% CI 2.5-8.4), and median OS (mOS) of 18.8 months. In 10 patients, where both RECIST and PERCIST evaluation was available, the ORR was 10% for both; however, the PFS was longer for PERCIST compared to RECIST, 3.1 and 2.4 months, respectively. A poor agreement between the criteria was observed at all assessments (Cohen's kappa ≤0), yet they differed significantly only at the first on-treatment imaging ( P  = 0.037). Elevated baseline LDH and age were associated with an increased risk for RECIST progression, while lymphocyte decrease after the first infusions correlated to reduced risk of RECIST progression. Detectable ctDNA at baseline did not correlate with progression. Early response to tebentafusp may be incompletely captured by conventional imaging, leading to a need to consider both tumor morphology and metabolism., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved.

Background: Targeted therapy (TT) of BRAF V600 mutated unresectable melanoma with inhibitors of the MAPK pathway achieves response rates of up to 76%, but most patients develop secondary resistance. Albeit TT is strikingly efficacious during the first days of treatment, even in advanced cases, long-term survival is highly unlikely, especially in patients with unfavorable baseline characteristics like elevated lactate dehydrogenase (LDH). In patients treated with anti-PD-1 immune checkpoint inhibitors, elevated baseline metastatic growth rate (MGR) was the most important prognostic factor. Here, we aimed at investigating the prognostic impact of MGR in patients with unresectable melanoma receiving TT., Methods: Clinical records of 242 patients with at least one measurable target lesion (TL) receiving TT at seven skin cancer centers were reviewed. Baseline MGR was determined measuring the largest TL at baseline and at one earlier timepoint., Results: Overall survival (OS) and progression-free survival (PFS) were significantly impaired in patients with an MGR > 3.9 mm/month (median OS: 11.4 vs. 35.5 months, P < 0.0001; median PFS: 4.8 vs. 9.2 months, P < 0.0001). Multivariable analysis of OS and PFS revealed that the prognostic impact of elevated MGR was independent of LDH, presence of brain and liver metastases, tumor burden, and line of treatment. The prognostic significance of elevated MGR was highest in patients with normal LDH., Conclusions: Baseline MGR is an important independent prognostic marker for OS and PFS in melanoma patients treated with TT. Its implementation in clinical routine is easy and could facilitate the prognostic stratification., Competing Interests: Declaration of Competing Interest N.B.W. has participated in advisory board meetings for Novartis, Pierre Fabre, and Sanofi, and received speaker fees from Sanofi, outside the submitted work. A.Oe. has received consultant fees from MSD and Bristol-Myers Squibb; has participated in advisory board meetings for MSD and Bristol-Myers Squibb. T.A. received institutional grants from SkylineDx, Neracare, Novartis, Sanofi, and consulting fees from Novartis, Neracare, BMS, CeCaVa and Chemosat, outside the submitted work. A.F. served as a consultant to Novartis, MSD, BMS, Pierre-Fabre and Immunocore; received travel support from Novartis, BMS, Pierre-Fabre, and received speaker fees from Novartis, BMS and MSD and reports institutional research grants from BMS Stiftung Immunonkologie, outside the submitted work. U.L. has received consultancy fees from MSD, Novartis, and Roche; has participated in advisory board meetings for MSD, Novartis, and Roche; has received honoraria from MSD, Novartis, and Roche. P.T. has received honoraria and/or consultancy fees from Bristol-Myers Squibb, Curevac, Merck, MSD, Novartis, Pierre Fabre, Roche, and Sanofi; has received travel support from Bristol-Myers Squibb and Pierre-Fabre. J.M. has received consultancy fees from Merck/Pfizer, MSD, Amgen, Novartis, Bristol-Myers Squibb, and Pierre Fabre; has participated in advisory board meetings for Merck/Pfizer, MSD, Amgen, Novartis, Bristol-Myers Squibb, and Pierre Fabre; has received travel support from Ultrasun, L′Oreal, MSD, Bristol-Myers Squibb, and Pierre Fabre. C.L. has received consultancy fees from, has participated in advisory board meetings for, has received speaker’s fees, and/or has received travel reimbursements from Roche, Pierre Fabre, Novartis, Bristol-Myers Squibb, Merck, MSD, Biontech, Almiral Hermal, Kyowa Kirin, Sun Pharma and Sanofi. C.G. has received personal fees from CeCaVa, MSD, NeraCare and Philogen. F.M. has received speaker’s fees from, has received travel support from, and has participated in advisory board meeting for Novartis, Roche, Bristol-Myers Squibb, MSD and Pierre Fabre; has received research funding from Novartis and Roche. T.K.E. has received consultancy fees from Philogen, Bristol-Myers Squibb, Novartis, Roche, Merck, and Sanofi; has participated in advisory board meetings for CureVac, Philogen, Bristol-Myers Squibb, Novartis, Roche, and Sanofi. L.F. has received grant funding from the Swiss National Science Foundation, Swiss Cancer League, Hookipa Pharma and Novartis Foundation; has participated in advisory board meetings for Novartis and Bristol-Myers Squibb. M.M.L., K.K., L.R., M.F., N.R., R.S., C.Z., C.E., S.K., B.K., W.H., and A.C. have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Ltd.)