Charlée Nardin

Liver resection and ablation for metastatic melanoma: A single center experience

The median survival for patients with stage IV metastatic melanoma is usually limited to approximately 1 year. In the case of liver metastasis, resection and ablation can achieve long‐term survival. This study aimed to describe the outcomes after liver resection or ablation for metastatic melanoma to the liver and identify preoperative prognostic factors.

The metabolic/pH sensor soluble adenylyl cyclase is a tumor suppressor protein

cAMP signaling pathways can both stimulate and inhibit the development of cancer; however, the sources of cAMP important for tumorigenesis remain poorly understood. Soluble adenylyl cyclase (sAC) is a non-canonical, evolutionarily conserved, nutrient- and pH-sensing source of cAMP. sAC has been implicated in the metastatic potential of certain cancers, and it is differentially localized in human cancers as compared to benign tissues. We now show that sAC expression is reduced in many human cancers. Loss of sAC increases cellular transformation in vitro and malignant progression in vivo. These data identify the metabolic/pH sensor soluble adenylyl cyclase as a previously unappreciated tumor suppressor protein.

BRAF mutation screening in melanoma: is sentinel lymph node reliable?

As the detection of the BRAF V600E mutation has a direct impact on treatment decision, an accurate screening for BRAF mutations in patients with advanced or metastatic melanoma is mandatory. Nevertheless, BRAF oncogene mutation status between different samples from the same patient has been studied with conflicting results. This study investigated the intrapatient homogeneity of BRAF mutation status using pyrosequencing in primary tumors and different metastatic sites of melanoma patients. Paired samples of lymphatic, visceral, and subcutaneous metastases and primary melanoma from 45 metastatic melanoma patients were tested for BRAF mutations using a pyrosequencing assay and by Sanger sequencing. Overall, sequencing for BRAF mutation status was performed in 114 paired samples from 45 patients. Eighteen patients (40%) carried a BRAF mutation, including BRAF V600E (12/18), BRAF V600K (5/18), and BRAF V600R (1/18) mutations. Multiple BRAF mutations (V600E and V600K) were found in one patient. Among the patients with BRAF mutations, a good agreement in BRAF mutation status was found between the first and second tumor samples genotyped (91%; Cohen’s &kgr; coefficient: 0.81). Discordance in BRAF mutation status was found only in four patients, involving all three patients in whom sentinel lymph node (SLN) metastases were sampled. These SLNs exhibited a wild-type genotype and were discordant with the other BRAF-mutated samples found in the same patient. The intrapatient BRAF status was predominantly homogeneous. However, SLN genotyping using pyrosequencing might be inaccurate in determining the actual mutation status of melanoma. Further studies are required to confirm the lack of reliability of SLN.

Long-term adverse event: inflammatory orbitopathy induced by pembrolizumab in a patient with metastatic melanoma

SummaryThe recent advent of immune checkpoint inhibitors (ICI), including anti-programmed cell death 1 protein (anti-PD-1) agents has revolutionized the therapeutic approach of metastatic malignancies. Yet, ICI can disrupt immune tolerance resulting in enhanced immune activation in normal tissues with significant toxicity. A dysregulated activation of T-cells directed to normal tissues stands as the main mechanism of immune-related adverse events (irAE). To date, only two cases of immune-related inflammatory orbitopathy related to anti-PD-1 agents have been reported. This rare immune adverse event usually occurred early after ICI initiation. Here, we report the first case of late inflammatory orbitopathy occurring in a melanoma patient treated with pembrolizumab. Consequently, the occurrence of irAE under ICI should be monitored, even late after treatment instauration.