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Purpose: Bilateral vocal cord dysfunction (bVCD) is a rare but feared complication of thyroid surgery. This long term retrospective study determined the effect of intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) during thyroid surgeries with regard to the rate of bVCD and evaluated the frequency as well as the outcome of staged operations. Methods: Retrospective analysis of prospectively documented data (2000–2019) of a tertiary referral centers’ database. IONM started in 2000 and, since 2010, discontinuation of surgery was encouraged in planned bilateral surgeries to prevent bVCD, if non-transient loss of signal (ntLOS) occurred on the first side. Datasets of the most recent 40-month-period were assessed in detail to determine the clinical outcome of unilateral ntLOS in planned bilateral thyroid procedures. Results: Of 22,573 patients, 65 had bVCD (0.288%). The rate of bVCD decreased from 0.44 prior to 2010 to 0.09% after 2010 (p < 0.001, Chi2). Case reviews of the most recent 40 months period identified ntLOS in 113/3115 patients (3.6%, 2.2% NAR), of which 40 ntLOS were recorded during a planned bilateral procedure (n = 952, 2.1% NAR). Of 21 ntLOS occurring on the first side of the bilateral procedure, 15 procedures were stopped, subtotal contralateral resections were performed, and thyroidectomy was continued in 3 patients respectively, with the use of continuous vagal IONM. Eighteen cases of VCD were documented postop, and all but one patient had a full recovery. Seven patients had staged resections after 1 to 18 months (median 4) after the first procedure. Conclusion: IONM facilitates reduced postoperative bVCD rates. IONM is, therefore, recommendable in planned bilateral procedures. The rate of non-complete bilateral surgery after intraoperative non-transient LOS was 2%.
Purpose: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy.
Methods: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected.
Results: 413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI.
Conclusion: A broad range of actionable alterations was targeted with available molecular therapeutics.
However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary.