Search

Erdheim-Chester disease (ECD) is an exceedingly rare non-Langerhans cell CD68+ CD1a- S100- histiocytic multi-organ disease. Diagnosis of ECD is often delayed due to non-specific radiographic findings and heterogeneous lesional tissue. Increasingly, the role of genomic alterations is being recognized for both diagnosis and treatment of ECD. More than half of ECD patients harbor the BRAFV600E mutation. Evaluation for this mutation be can falsely negative on immunohistochemical staining and confirmation with molecular analyses is recommended. We present a case of the 44 year-old male with BRAFV600E-positive ECD treated successfully with steroids followed by single-agent dabrafenib.

Purpose: To report a case of Vogt-Koyanagi-Harada (VKH)-like uveitis under treatment with Dabrafenib and Trametinib for metastatic malignant melanoma, representing the longest follow-up (49 months) with retinal multimodal imaging. Methods: Retrospective case report. Results: A 49-year-old female with metastatic relapsing cutaneous malignant melanoma presented with blurry vision in both eyes for 1 week. She had been treated with Dabrafenib and Trametinib for 2 months. Fundus examination detected serous retinal detachments (SRDs) and hyperemic optic disks. Spectral-domain optical coherence tomography (SD-OCT) revealed SRDs, retinal pigment epithelium undulations, choroidal thickening, and loss of normal choroidal vascular architecture. The patient was diagnosed with VKH-like uveitis secondary to targeted agents since systemic investigations were unremarkable. Dabrafenib and Trametinib were discontinued, and pulse steroid treatment was started. Following the improvement of retinal and choroidal signs, the same targeted agents were restarted 6 weeks later. No recurrence of uveitis occurred during 49 months of follow-up; however, the convalescent phase findings of VKH were observed in the fundus examination. The systemic status of the patient, who is still using Dabrafenib and Trametinib, is stable. Conclusion: Although the mechanism is still unknown, the development of VKH-like uveitis secondary to targeted therapy may indicate successful tumor control in patients with metastatic melanoma. Providing effective immunosuppression with corticosteroids and making necessary dose modifications with a multidisciplinary approach may extend the survival of patients. [ABSTRACT FROM AUTHOR]

Introduction: Most pediatric low-grade-gliomas (LGG) and some high-gradegliomas (HGG) have alterations in the RAS/MAPK pathway. Promising high tumor response rates were achieved using BRAF/MEK inhibitors, however data on their use in low-middle-income-countries (LMICs) are limited. Methods: We retrospectively reviewed our Jordanian experience of using compassionate BRAF/MEK inhibitors in treating children with gliomas. We reviewed patients' clinical characteristics, tumor response, and side effects. Results: Twenty patients (13 males, 7 females) were identified. Median age at diagnosis was 8.3 years (0.3-18.9years). There were fifteen LGGs, three HGGs and two grade-2 pleomorphic xanthoastrocytoma (PXA-2). Fifteen tumors were supratentorial, three posterior fossa/brainstem, one diffuse-glioneuronal tumor (DLGNT) and one spinal. Five tumors were metastatic. Except for one patient with neurofibromatosis, ten patients underwent partial resection and nine had biopsy. All patients, except three, received BRAF/MEK inhibitors after initial standard chemo/radiotherapy. Seven LGGs had BRAF-mutation, six had BRAF-fusion, and two were empirically treated (one neurofibromatosis and one DLGNT). Fourteen LGGs were treated with 1-4 chemotherapy regimens before BRAF/MEK inhibitors' use; all had partial/stable response on targeted therapy at a median of 1.9 years (0.5-5.4years). Two patients with BRAFv600E-mutated/CDKN2A deleted PXA-2, had progression following resection, and experienced stable/partial response at 9 months of dabrafenib use. Two patients with HGGs had BRAFv600E-mutation, and one had an FGFR-mutation. All three patients with HGG had temporary stable/partial response, two with significant clinical improvement. At a median of 2.7 years (1.3-3.2years), all patients experienced tumor progression, and two died. Eight patients (40%) developed acneiform rash, three (15%) paronychia, and one had significant panniculitis and fatigue. Six patients (30%) needed dose-reduction. Nine patients had temporary drug interruptions [due to side effects (5) and drug shortage (4)]. Two patients who stopped trametinib due to side effects (significant acneiform rash/paronychia and intracranial bleeding) did not experience progression. Conclusions: Our experience with BRAF/MEK inhibitors' use was positive achieving response in all LGGs and provided sustained response with good quality of life for patients with HGG. Cost effectiveness analyses and patients' satisfaction comparisons with chemotherapy are needed to evaluate the routine use of these drugs in LMICs. [ABSTRACT FROM AUTHOR]

Purpose: BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. Dabrafenib and trametinib showed promising antitumor activity in patients with BRAFV600E-mutated metastatic melanoma and non–small cell lung cancer. This study aimed to evaluate the efficacy and safety of dabrafenib and trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer. Materials and Methods: This was a retrospective study to evaluate the efficacy of dabrafenib and trametinib in patients with metastatic BRAFV600E-mutated PTC. The patients received dabrafenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of dabrafenib and trametinib. Results: Between December 2019 and January 2022, 27 PTC patients including eight patients with poorly differentiated or anaplastic transformation, received dabrafenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients. Conclusion: Dabrafenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAFV600E-mutated metastatic PTC required a dose reduction. [ABSTRACT FROM AUTHOR]