Characterization of 164 patients with NRAS mutated non-small cell lung cancer (NSCLC).

BACKGROUND: NRAS mutations are observed in less than 1% of non-small cell lung cancer (NSCLC). Clinical data regarding this rare subset of lung cancer are scarce and response to systemic treatment such as chemotherapy or immune checkpoint inhibitors (ICI) has never been reported. METHODS: All consecutive patients with an NRAS mutated NSCLC, diagnosed between August 2014 and November 2020 in 14 French centers, were included. Clinical and molecular data were collected and reviewed from medical records. RESULTS: Out of the 164 included patients, 106 (64.6%) were men, 150 (91.5%) were current or former smokers, and 104 (63.4%) had stage IV NSCLC at diagnosis. The median age was 62 years, and the most frequent histology was adenocarcinoma (81.7%). NRAS activating mutations were mostly found in codon 61 (70%), while codon 12 and 13 alterations were observed in 16.5% and 4.9% of patients, respectively. Programmed death ligand-1 expression level <1%/1-49%/≥50% were respectively found in 30.8%/27.1%/42.1% of tumors. With a median follow-up of 12.5 months, median overall survival (OS) of stage IV patients was 15.3 months (95% CI 9.9-27.6). No significant difference in OS was found according to the type of mutation (codon 61 vs. other), HR = 1.12 (95% CI 0.65-1.95). Among stage IV patients treated with platinum-based doublet (n = 66), ICI (n = 48), or combination of both (n = 10), objective response rate, and median progression free survival were respectively 45% and 5.8 months, 35% and 6.9 months, 70% and 8.6 months. CONCLUSION: NRAS mutated NSCLC are characterized by a high frequency of smoking history and codon 61 mutations. Further studies are needed to confirm the encouraging outcome of immunotherapy in combination with chemotherapy.

Novel therapies for malignant pleural mesothelioma.

Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments.

Real-time light dosimetry for intra-cavity photodynamic therapy: Application for pleural mesothelioma treatment.

Complete and homogeneous illumination of the target is necessary for the success of a photodynamic therapy (PDT) procedure. In most applications, light dosimetry is done using detectors placed at strategic locations of the target. In this study we propose a novel approach based on the combination of light distribution modeling with spatial localization of the light applicator for real time estimation and display of the applied dose on medical images. The feasibility approach is demonstrated for intrapleural PDT of malignant pleural mesothelioma.

Illumination profile characterization of a light device for the dosimetry of intra-pleural photodynamic therapy for mesothelioma.

BACKGROUND: Complete and homogeneous illumination of the pleural cavity is essential to the success of photodynamic therapy (PDT) for mesothelioma, but remains a challenge. Knowing the repartition and propagation of light around the light applicator could be the first step towards optimizing dosimetry. Here we propose a characterization method of the illumination profile of a specific light device. METHODS: The light wand, made of a cylindrical diffuser located inside an endotracheal tube, was fixed in a tank filled with dilute 0.01% intralipid. Light dosimetry was performed around the tip of the wand using two complementary methods: direct measurements of light power with an isotropic probe and measurements of light distribution characterization. RESULTS: Dosimetry with the isotropic probe showed an ellipse-shaped illumination. An optimized effective attenuation coefficient was deduced. Combined with the spatial representation, a theoretical illumination profile was established with iso-surfaces of fluence rate, defining a gradient light dose according to the distance from the diffuser. CONCLUSION: A theoretical illumination profile of a light device was established and could be part of an intra-operative dosimetry system to improve light delivery during intrapleural PDT.

Intrapleural Photodynamic Therapy for Mesothelioma: What Place and Which Future?

In the surgical multimodal management of malignant pleural mesothelioma, it seems crucial to proceed with an efficient local adjuvant treatment to kill residual tumor cells. Intrapleural photodynamic therapy has recently emerged as a potential candidate in this goal. In this review, we analyzed and classified 16 articles in which patients with malignant pleural mesothelioma received intrapleural photodynamic therapy after maximal surgical resection. The toxicity, effect on survival, and development of the technique were assessed. After two decades of clinical studies, intrapleural photodynamic therapy after surgical resection became a safe treatment that significantly improved the survival of patients.