A Case Series of Two Patients Presenting With Pericardial Effusion as First Manifestation of Non-Small Cell Lung Cancer With BRAF Mutation and Expression Of PD-L1

Abstract

Lung cancer is the number one cause of cancer-related deaths in the United States. Involvement of pericardium occurs once cancer has progressed to stage IV which can cause massive effusion in the pericardial sac. This can lead to cardiac tamponade which can be fatal very quickly if untreated. The following is a two patient case series in which both patients presented with large pericardial effusion. The first patient sought medical attention due to new onset palpitations and was found to have hemorrhagic pericardial effusion and pulmonary embolism (PE). The second patient presented with shortness of breath. Investigations revealed that she had pericardial and pleural effusions along with multiple metastases throughout the body. Both patients ended up with a diagnosis of non-small cell lung cancer (NSCLC) with BRAF mutation. One patient had V600E mutation; other patient had a variant p.D594N mutation. Both patients also had expression of PD-L1.

Metastatic Melanoma Patient–Derived Xenografts Respond to MDM2 Inhibition as a Single Agent or in Combination with BRAF/MEK Inhibition

“…Similar results were obtained in a small Phase I/2 clinical trial testing KRT-232 with trametinib and/or dabrafenib (NCT02110355), where patients with TP53 wt metastatic cutaneous melanoma were treated with KRT-232 at 120, 180 or 240 mg QD (7 days of each 3 week cycle) in combination with T (BRAF nonV600-mutant ) or D+T (BRAF V600-mutant ). KRT-232 + T was found to reduce tumor size in 73% of the patients with metastatic cutaneous melanoma expressing BRAF nonV600-mutant , with 13% (2/15) showing a greater than 30% reduction in size according to the RECIST criteria (44,45). Furthermore, 100% (6/6) of patients with BRAF V600-mutant melanoma treated with KRT-232 in combination with trametinib or dabrafenib had a reduction in tumor size, with 67% (4/6) patients having a decrease in tumor size of greater than 30%.…”

“…In contrast to the high prevalence of V600 BRAF mutations in the PDX tumors that were resistant to KRT-232, all of the PDX tumors that responded to KRT-232 lacked the BRAF V600 mutation, although and hairy cell leukemia, none of the other mutations have been reported and there are no data on the biological significance of these mutations (43)(44)(45). Amplification of the BRAF gene also occurred in the PDX tumors, but occurred in equal percentages in both the PDX tumors that were resistant to KRT-232 proteins involved in the regulation of apoptosis (61).…”

“…Further analysis of PDX1129 by NGS identified two mutations in BRAF (D549N and K483T). While the BRAF p.D549N is of unknown significance, it has been previously identified in the NZM41 cell line and in other melanomas, colorectal and lung carcinomas, in addition to hairy cell leukemia (42) (43)(44)(45). PDX2316 also was retrospectively analyzed by NGS and was found to lack mutations in BRAF and NRAS, although mutations in NF1, CDKN2A, MTOR, and KIT were detected.…”

Multiple primary malignant neoplasms: A case report and literature review

“…The ORR, DCR and median PFS time of the patients who were treated with dabrafenib and trametinib were 63, 79% and 9.7 months, respectively, and 65% of the patients achieved a PFS time of >6 months (17). Thus, the combination of MEK inhibitors with BRAF inhibitors may demonstrate improved results compared with BRAF inhibitors alone (18). The patient in the present case report was diagnosed with NSCLC harboring a BRAF V600E mutation.…”

Lung cancer classification based on CT scan image by applying FCM segmentation and neural network technique

“…This report is based on estimates for one year in 2020 [4]. This disease is characterized by pain accompanied by shortness of breath because the cancer cells fill the space in the lungs, and the capacity of the lungs for air storage is getting narrower [5]. This disease is also a frequent cause of other cancers because it spreads rapidly in the body and in the lungs [6].…”