Background: Thyroid cancer is the most common malignancy of the endocrine system, accounting for ~ 5% of all thyroid nodules and 1% of all systemic malignancies. BRAF mutations, primarily p.V600E hot spot mutations, are found in 60 - 70% of papillary thyroid cancer cases (PTC) and in 33 - 40% of fatal anaplastic thyroid cancers (ATC), also called poorly differentiated thyroid cancer. Dabrafenib was approved by the United States Food and Drug Administration (FDA) in 2018 to be applied in combination with trametinib for unresectable advanced or metastatic anaplastic thyroid cancer harboring the BRAFV600E mutation. Unfortunately, there are few reports on the pathophysiology, molecular mechanism, and risk factors of interstitial lung disease induced by combined BRAF- and MEK-targeted therapy.
Case presentation: We treated a 73-year-old man with metastatic BRAFV600E-mutated poorly differentiated thyroid cancer using the combination of dabrafenib and trametinib. Although a significant morphologic tumor response was observed in our patient using combined BRAF- and MEK-targeted therapy, he presented with non-febrile respiratory failure, and his chest computed tomography (CT) revealed bilateral reticulation and pleural effusion. Withdrawal from dabrafenib-trametinib and administration of methylprednisolone rapidly improved his respiratory status and imaging features.
Conclusion: The mechanisms of lung disease after the combined treatment with dabrafenib and trametinib are unclear. We hypothesized that dual-targeted therapy with a BRAF inhibitor, dabrafenib, and a MEK inhibitor, trametinib, might prevent the regeneration and proliferation of fibrotic epithelium in lung disease by blocking downstream proliferative signals.
Objectives: To evaluate the representativeness of the German Oncology Dynamics (OD) dataset by comparing its projected patient population structure with that outlined in published epidemiological literature.
Materials and methods: The OD is an international cross-sectional semi-retrospective survey collecting anonymized patient cases from a representative panel of physicians via a web-based questionnaire; the cases are quality-checked and projected to the drug-treated prevalence using physician workload information. The present study verifies the OD 2018 projected patient proportions by indication and sex against prevalence figures in IARC's Globocan and the Cancer in Germany report by the Robert Koch Institute. Additionally, age group and metastasis presence distributions in gonadotropin-releasing hormone analog (GnRHa)-treated prostate cancer patients are compared with the findings of a registry-based study: Retrospective Analysis of Patients with Prostate Cancer Initiating GnRH Agonists/Antagonists Therapy Using a German Claims Database: Epidemiological and Patient Outcomes by Hupe et al. [3].
Results: The OD demonstrated a cancer type distribution similar to the comparator sources. Cancer-specific sex distribution differences could be attributed to real-world diagnosis and treatment patterns. The age group distributions of GnRH-treated prostate cancer patients did not differ significantly between the OD and the Hupe et al. [3] study according to confidence interval comparisons and a Kolmogorov-Smirnov test.
Conclusion: Projected patient distributions for the OD Germany were similar to those documented in the published literature. The dissimilarities can be attributed to the low drug-treated prevalence of some cancer types and sex-specific diagnosis timeline differences. Further investigations are needed to verify the reliability of histological biomarker data as well as patient demographics in other countries.
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