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Neonatal thyrotoxicosis (hyperthyroidism) is less prevalent than congenital hypothyroidism; however, it can lead to significant morbidity and mortality if not promptly recognized and adequately treated. Most cases are transient, secondary to maternal autoimmune hyperthyroidism (Graves disease [GD]). This article summarizes recommendations for screening and management of hyperthyroidism in both the fetal and neonatal periods, with a focus on neonatal thyrotoxicosis secondary to maternal GD. Early monitoring and treatment are crucial for optimizing short-term and long-term patient outcomes.

Until recently, platinum-based chemotherapy has represented the benchmark for the treatment of extensive disease small-cell lung cancer (ED-SCLC). ED-SCLC patients are often diagnosed with poor performance status (PS ≥2) and/or compromised organ functions. In fact, up to 63% of ED-SCLC has extensive liver involvement at diagnosis, which correlates with a poor prognosis. Whether to treat patients with tumor-related organ failure is still debated and the selection of those who could benefit from chemotherapy is crucial. Moreover, severe liver impairment contraindicates the administration of etoposide. Among 74 consecutive ED-SCLC patients followed at our institution from January 2017 to November 2019, three patients received single-agent carboplatin as a first-line treatment due to liver failure. We provide a brief description of a former heavy smoker 70-year-old man who was diagnosed with ED-SCLC and severe liver involvement leading to liver failure. The patient received a first-line treatment with single-agent carboplatin, obtaining a partial response, clinical benefit and the normalization of laboratory test, which documented the complete recovery of liver function. The intent of our work is to highlight the feasibility of single-agent carboplatin in ED-SCLC patients with tumor-related hepatic failure but preserved Eastern Cooperative Oncology Group PS, suggesting that this therapeutic option should not be discouraged a priori. Indeed, the identification of specific tools guiding physicians in the selection of patients who might benefit from the treatment is remarkably needed; meanwhile, the use of available prognostic score (e.g. Manchester score) might be of great value and should be considered in clinical practice. Anti-Cancer Drugs 32: 755-757 Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Novel treatment strategies incorporating PD-1/PD-L1 inhibitors in the first-line setting of advanced non-small-cell lung cancer (NSCLC) provided relevant improvements in survival outcomes. Among NSCLC patients with PD-L1 tumor proportion score ≥50%, identifying the ones to be addressed to pembrolizumab monotherapy or chemo-immunotherapy combinations is a matter of debate, taking into account the risks of overtreatment and toxicity. Here we report the clinical stories of four NSCLC patients with PD-L1 tumor proportion score ≥50% and good performance status, sharing high tumor burden including serosal involvement. After having rapidly progressed on first-line PD-1/PD-L1 inhibitors, they achieved major clinical and radiological response to pembrolizumab-chemotherapy combination. These cases prove the feasibility and effectiveness of salvage chemo-immunotherapy in pembrolizumab-refractory NSCLC patients.

Hyperammonemic encephalopathy represents a rare adverse effect of several chemotherapeutic agents, occurring in about 0.7% of patients treated with fluoropyrimidines, and it is independent from dihydropyrimidine dehydrogenase deficiency. Instead, its physiopathology is linked to the inhibition of Krebs cycle by fluoroacetate, leading to decreased ATP production, and to the inhibition of the urea cycle. Oxaliplatin seems to induce hyperammonemic encephalopathy in a similar way, acting on mitochondria. Here, we report the intriguing case of acute hyperammonemic encephalopathy in a 65-year-old patient with preserved liver function, who was treated with oxaliplatin and capecitabine for a metastatic, G1, atypical lung carcinoid. We reviewed the literature and found very few reports of oxaliplatin or capecitabineinduced hyperammonemic encephalopathy. Out of five cases of capecitabine-related hyperammonemic encephalopathy analyzed (four plus our case), median time to hyperammonemic encephalopathy onset was 6 days, with median serum ammonia levels of 213 μmol/L. Oxaliplatin-related hyperammonemic encephalopathy analyzed cases were three (two plus ours), with a median time to hyperammonemic encephalopathy of 11 days and median serum ammonia levels of 167 μmol/L. Identified predisposing factors for chemotherapy-induced hyperammonemia, such as dehydration, liver and renal impairment, infections, and sarcopenia were absent in our case. We hypothesize that the combination of a platinum-derivative and a fluoropyrimidine multiplies the risk of hyperammonemic encephalopathy, even in the absence of predisposing factors nor impaired liver function. We therefore suggest to always consider the risk of hyperammonemia when starting fluoropyrimidinesbased chemotherapy, especially combined with platinumderivatives, and to timely investigate neurologic symptoms monitoring ammonia serum levels. Anti-Cancer Drugs 31: 1103-1105.

Lung cancer is the leading cause of cancer death worldwide. In the past decade EGFR, ALK and ROS1 TKIs lead to an unprecedented survival improvement of oncogene-addicted NSCLC patients, with better toxicity profile compared to chemotherapy. In recent years the implementation of high-throughput sequencing platforms led to the identification of uncommon molecular alterations in oncogenic drivers, such as BRAF, MET, RET, HER2 and NTRK. Moreover, newly developed drugs have been found to be active against hard to target drivers, such as KRAS. Specific TKIs targeting these genomic alterations are currently in clinical development and showed impressive activity and survival improvement, leading to FDA-accelerated approval for some of them. However, virtually all patients develop resistance to TKIs by on-target or off-target mechanisms. Here we review the clinicopathological features, the emerging targeted therapies and mechanisms of resistance and strategies to overcome them of KRAS, BRAF, MET, RET, HER2 and NTRK-addicted advanced NSCLCs.