PORT: A Randomized, Cross-Over, Phase 2 Study of Melflufen Peripheral Versus Central Intravenous Administration in Patients With Relapsed/Refractory Multiple Myeloma.

BACKGROUND: Melflufen, a first-in-class alkylating peptide-drug conjugate, rapidly enters tumor cells and metabolizes to melphalan. In previous studies, melflufen was administered via central venous catheter (CVC). However, administration by peripheral venous catheter (PVC) may be preferable. PATIENTS AND METHODS: PORT was a two-period, phase 2 crossover study of CVC versus PVC melflufen administration in patients with relapsed/refractory multiple myeloma. Adults with ≥ 2 prior therapies refractory to/intolerant of an immunomodulatory drug and a proteasome inhibitor were randomized 1:1 to weekly oral dexamethasone plus melflufen (40 mg) via CVC or PVC infusion on day 1 of 28-day cycle 1. In cycle 2, patients continued dexamethasone and crossed over to the other melflufen administration route. In cycle 3, all patients received melflufen until progression; PVC or CVC routes were allowed based upon investigator decision. Pharmacokinetic sampling was performed during and after melflufen infusion. Primary endpoints were melphalan pharmacokinetic parameters (Cmax, AUC(0-t), and AUC(0-∞)) and frequency and severity of PVC-related local reactions. RESULTS: The 90% CIs for adjusted geometric mean ratios for pharmacokinetic parameters following CVC versus PVC administration were within the 0.8-1.25 bioequivalence range (Cmax 0.946 [90% CI: 0.849, 1.053]; AUC(0-t) 0.952 [90% CI: 0.861, 1.053]; AUC(0-∞) 0.955 [90% CI: 0.863, 1.058]). In both arms, adverse events were primarily hematological and similar; no phlebitis or local infusion-related reactions occurred. CONCLUSION: Melflufen PVC and CVC administrations are bioequivalent based on melphalan pharmacokinetic parameters. Melflufen via PVC was well tolerated, with no infusion-related reactions or new safety signals and may represent an alternative route of administration.

Health-related quality of life in relapsed/refractory multiple myeloma treated with melflufen and dexamethasone: analyses from the phase III OCEAN study.

Not available.

ANCHOR: melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study.

Melphalan flufenamide (melflufen), a first-in-class, alkylating peptide-drug conjugate, demonstrated clinical benefit in combination with dexamethasone in triple-class refractory multiple myeloma (MM). The phase I/IIa ANCHOR study evaluated melflufen (30 or 40 mg) and dexamethasone (40 mg with daratumumab; 20 mg followed by 40 mg with bortezomib; dose reduced if aged ≥75 years) in triplet combination with daratumumab (16 mg/kg; daratumumab arm) or bortezomib (1.3 mg/m2; bortezomib arm) in patients with relapsed/refractory MM refractory to an immunomodulatory agent and/or a proteasome inhibitor and who had received one to four prior lines of therapy. Primary objectives were to determine the optimal dose of melflufen in triplet combination (phase I) and overall response rate (phase IIa). In total, 33 patients were treated in the daratumumab arm and 23 patients received therapy in the bortezomib arm. No dose-limiting toxicities were reported at either melflufen dose level with either combination. With both triplet regimens, the most common grade ≥3 treatment-emergent adverse events were thrombocytopenia and neutropenia; thrombocytopenia was the most common treatment-emergent adverse event leading to treatment discontinuation. In the daratumumab arm, patients receiving melflufen 30 mg remained on treatment longer than those receiving the 40-mg dose. In the daratumumab arm, the overall response rate was 73% and median progression-free survival was 12.9 months. Notably, in the bortezomib arm, the overall response rate was 78% and median progression-free survival was 14.7 months. Considering the totality of the data, melflufen 30 mg was established as the recommended dose for use with dexamethasone and daratumumab or bortezomib for future studies in relapsed/refractory MM.

Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study.

Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone was approved in Europe for use in patients with triple-class refractory relapsed/refractory multiple myeloma (RRMM) with ≥3 prior lines of therapy and without prior autologous stem cell transplantation (ASCT) or with a time to progression >36 months after prior ASCT. The randomized LIGHTHOUSE study (NCT04649060) assessed melflufen plus daratumumab and dexamethasone (melflufen group) versus daratumumab in patients with RRMM with disease refractory to an immunomodulatory agent and a proteasome inhibitor or who had received ≥3 prior lines of therapy including an immunomodulatory agent and a proteasome inhibitor. A partial clinical hold issued by the US Food and Drug Administration for all melflufen studies led to financial constraints and premature study closure on February 23rd 2022 (data cut-off date). In total, 54 of 240 planned patients were randomized (melflufen group, N=27; daratumumab group, N=27). Median progression-free survival (PFS) was not reached in the melflufen group versus 4.9 months in the daratumumab group (Hazard Ratio: 0.18 [95% Confidence Interval, 0.05-0.65]; P=0.0032) at a median follow-up time of 7.1 and 6.6 months, respectively. Overall response rate (ORR) was 59% in the melflufen group versus 30% in the daratumumab group (P=0.0300). The most common grade ≥3 treatment-emergent adverse events in the melflufen group versus daratumumab group were neutropenia (50% vs. 12%), thrombocytopenia (50% vs. 8%), and anemia (32% vs. 19%). Melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM and a safety profile comparable to previously published melflufen studies.

Melflufen in relapsed/refractory multiple myeloma refractory to prior alkylators: A subgroup analysis from the OCEAN study.

Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS), but not overall survival (OS), versus pomalidomide plus dexamethasone in relapsed/refractory multiple myeloma in the OCEAN study. Time to progression (TTP) <36 months after a prior autologous stem cell transplantation (ASCT) was a negative prognostic factor for OS with melflufen. This post hoc exploratory analysis evaluated patients refractory to prior alkylators (e.g., cyclophosphamide and melphalan) in OCEAN. In 153 patients refractory to prior alkylators (melflufen, n = 78; pomalidomide, n = 75), the melflufen and pomalidomide arms had similar median PFS (5.6 months [95% CI, 4.2-8.3] vs. 4.7 months [95% CI, 3.1-7.3]; hazard ratio [HR], 0.92 [95% CI, 0.63-1.33]) and OS (23.4 months [95% CI, 14.4-31.7] vs. 20.0 months [95% CI, 12.0-28.7]; HR, 0.92 [95% CI, 0.62-1.38]). Among alkylator-refractory patients with a TTP ≥ 36 months after a prior ASCT or no prior ASCT (melflufen, n = 54; pomalidomide, n = 53), the observed median PFS and OS were longer in the melflufen arm than the pomalidomide arm. The safety profile of melflufen was consistent with previous reports. These results suggest that melflufen is safe and effective in patients with alkylator-refractory disease, suggesting differentiated activity from other alkylators.

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies.

INTRODUCTION: Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN. METHODS: These analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022). RESULTS: In OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports. CONCLUSION: These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).

Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study.

BACKGROUND: Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. METHODS: In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0-2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing. FINDINGS: Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60-72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61-72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6·8 months (95% CI 5·0-8·5; 165 [67%] of 246 patients had an event) in the melflufen group and 4·9 months (4·2-5·7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0·79, [95% CI 0·64-0·98]; p=0·032), at a median follow-up of 15·5 months (IQR 9·4-22·8) in the melflufen group and 16·3 months (10·1-23·2) in the pomalidomide group. Median overall survival was 19·8 months (95% CI 15·1-25·6) at a median follow-up of 19·8 months (IQR 12·0-25·0) in the melflufen group and 25·0 months (95% CI 18·1-31·9) in the pomalidomide group at a median follow-up of 18·6 months (IQR 11·8-23·7; HR 1·10 [95% CI 0·85-1·44]; p=0·47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs 26 [11%] of 246 in the pomalidomide group), neutropenia (123 [54%] vs 102 [41%]), and anaemia (97 [43%] vs 44 [18%]). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]). 27 [12%] patients in the melflufen group and 32 [13%] in the pomalidomide group had fatal treatment-emergent adverse events. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia). INTERPRETATION: Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. FUNDING: Oncopeptides AB.

Patient-reported outcomes in relapsed/refractory multiple myeloma treated with melflufen plus dexamethasone: analyses from the Phase II HORIZON study.

Relapsed/refractory multiple myeloma (RRMM) is known to have a high burden of disease and complications associated with refractoriness to prior lines of therapy. Severe pain and fatigue symptoms and impairments in physical and emotional functioning have been strongly linked to reduced health-related quality of life (HRQoL) in patients with RRMM. Assessment of patient reported-outcome measures from the pivotal, Phase II HORIZON study (OP-106; NCT02963493) in patients with RRMM (n = 64) demonstrated that melphalan flufenamide (melflufen) plus dexamethasone treatment preserved HRQoL. Patients had clinically meaningful improvements, even after eight treatment cycles, in relevant scales such as global health status/QoL, physical functioning, emotional functioning, pain, and fatigue. Patients with triple-class-refractory disease (n = 50) displayed similar improvements. Patient-reported outcome deterioration was delayed for a substantial amount of time in patients who experienced a response to melflufen plus dexamethasone treatment relative to patients who did not experience a response. These findings support the notion that treatment with melflufen plus dexamethasone may sustain or improve HRQoL over time in patients with RRMM, including in patients with triple-class-refractory disease for whom outcomes are generally worse. The clinical benefits observed in patients from the HORIZON trial are encouraging and supportive of translation into real-world practice.

Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma.

PURPOSE: Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS: Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS: Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class-refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class-refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION: Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class-refractory and extramedullary disease.

ASTRIS: a global real-world study of osimertinib in >3000 patients with EGFR T790M positive non-small-cell lung cancer.

Aim: Osimertinib is a third-generation, irreversible, oral EGFR tyrosine kinase inhibitor. We report real-world effectiveness and safety data. Patients & methods: EGFR T790M positive advanced non-small-cell lung cancer adults, who received ≥1 prior EGFR tyrosine kinase inhibitor, received osimertinib 80 mg daily. Primary effectiveness outcome: overall survival. Secondary effectiveness outcomes included: investigator-assessed clinical response, progression-free survival, time-to-treatment discontinuation. Results: At data cutoff, 3015 patients had enrolled: 57.1% had investigator-assessed response (95% CI: 55.2-58.9). Median progression-free survival: 11.1 months (95% CI: 11.0-12.0) and median time-to-treatment discontinuation: 13.5 months (95% CI: 12.6-13.9). Interstitial lung disease/pneumonitis-like events reported in 28 (1%) patients. Conclusion: Osimertinib demonstrated clinical effectiveness similar to efficacy observed in the clinical trial program with no new safety signals.

Buccal bone thickness at dental implants in the aesthetic zone: A 1-year follow-up cone beam computed tomography study.

Sufficient buccal bone thickness (BBT) is important for an optimal aesthetic outcome of implant treatment in the aesthetic zone. The aim of the study was to assess BBT at dental implants placed in the aesthetic zone (incisor, canine or first premolar in the maxilla) (immediate or delayed, with or without immediate provisionalization) with cone beam computed tomography (CBCT) as a function of time. Eighty patients were divided into 4 groups according to size of the buccal bony defect (<5 or ≥5 mm) after removal of the tooth, and timing of implant placement and provisionalization. CBCTs were made 1 month and 1 year after placement of the implant crown. BBT varied from 0.79 mm to 2.12 mm at 1 month and from 0.71 mm to 2.04 mm at 1 year. Change of BBT between 1 month and 1 year was negligible. This study concluded that BBT at dental implants in the aesthetic zone appears to be stable for immediate and delayed placed implants after placement of the definitive crown, independent of the size of buccal bone defect prior to implant insertion and timing of provisionalization.

Immediate Single-Tooth Implant Placement in Bony Defects in the Esthetic Zone: A 1-Year Randomized Controlled Trial.

BACKGROUND: This study aims to assess, with regard to marginal bone level (MBL), whether the outcome of immediate implant placement in bony defects in the esthetic zone was non-inferior to delayed implant placement after 1 year. METHODS: Forty patients with a failing tooth in the esthetic zone and a labial bony defect of ≥5 mm after removal of a tooth were randomly assigned for immediate (n = 20) or delayed (n = 20) implant placement. Second-stage surgery and provisionalization occurred after 3 months of healing. Follow-up was at 1 month and 1 year after definitive crown placement. The study was powered to detect a difference in MBL of >0.9 mm. Buccal bone thickness, soft tissue peri-implant parameters, esthetic indices, and patient satisfaction were also assessed. RESULTS: One year after definitive crown placement, MBL loss was 0.56 ± 0.39 mm mesially and 0.74 ± 0.51 mm distally for the immediate placement group and 0.51 ± 0.43 mesially and 0.54 ± 0.45 distally mm for the delayed placement group, respectively (not significant). Regarding differences in means, non-inferiority was observed after 1 year (difference in mean for immediate versus delayed: mesially 0.04 mm [95% confidence interval (CI) = -0.22 to 0.30 mm, P = 0.40]; distally 0.21 mm [95% CI = -0.10 to 0.51 mm, P = 0.58]). No significant differences in the other outcome variables were observed. CONCLUSIONS: Immediate implant placement with delayed provisionalization was non-inferior to delayed implant placement with delayed provisionalization in labial bony defects of ≥5 mm regarding change in MBL. Although not powered for other outcome variables, no clinically relevant differences were observed in these variables.

Recurrence Rates After Surgical or Endovascular Treatment of Spinal Dural Arteriovenous Fistulas: A Meta-analysis.

BACKGROUND: There is an increasing tendency to treat spinal dural arteriovenous fistulas (SDAVFs) endovascularly despite the lack of clear evidence favoring embolization over surgery. OBJECTIVE: To compare the initial failure and recurrence rates of primary treatment of SDAVFs by surgery and endovascular techniques. METHODS: A meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was performed. All the English literature from 2004 onward was evaluated. From each article that compared the 2 treatment modalities, the odds ratio (OR) was calculated. Combined ORs were calculated with Review Manager 5.3 of The Cochrane Collaboration. RESULTS: A total of 35 studies harboring 1112 patients were assessed. Initial definitive fistula occlusion was observed in 588 of 609 surgical patients (96.6%; 95% confidence interval [CI], 94.8-97.8) vs 363 of 503 endovascularly treated patients (72.2%; 95% CI, 68.1-75.9; P < .001). The combined OR from 18 studies that assessed both treatment modalities (730 patients) was 6.15 (95% CI, 3.45-11.0) in favor of surgical treatment. Late recurrence (13 studies, 480 patients) revealed an OR of 3.15 (95% CI, 1.66-5.96; P < .001) in favor of surgery. In a subgroup, recurrence was reported in 10 of 22 patients (45%) treated with Onyx vs 8 of 35 (23%) treated with n-butyle-2-cyanoacrylate (OR, 2.51; 95% CI, 0.75-8.37; P = .13). CONCLUSION: Although hampered by inclusion of poor quality studies, this meta-analysis shows a definite advantage of primary surgical treatment of SDAVF over endovascular treatment in initial failure rate and late recurrences. The often-used argument that endovascular techniques have improved and therefore outweigh surgery is not supported by this meta-analysis.

Near total extirpation of vestibular schwannoma with salvage radiosurgery.

OBJECTIVES/HYPOTHESIS: The management of a sporadic vestibular schwannoma (VS) has changed with the introduction of stereotactic radiosurgery (SRS). Because functional outcome is important, particularly regarding the facial nerve, a policy of near-total surgical resection of a large-size VS has emerged, minimizing damage to the facial nerve. The debate remains whether the surgical remnant should be treated immediately or after established growth. STUDY DESIGN: Retrospective case series. METHODS: A consecutive cohort of 55 patients underwent a retrosigmoid craniotomy and near-total removal of a large-size VS at our university medical center between 2005 and 2011 and had a follow-up of a least 3 years. Documented growth of the VS remnant after surgery necessitating adjuvant SRS was the primary outcome measure using analysis of variance. RESULTS: In 45 patients (81.8%), a small tumor remnant was left during surgery. The mean preoperative tumor volume was 12.2 cm(3) (range, 1.13-50.16 cm(3)); the mean volume of the remnant was 0.22 cm(3) (range, 0-1.52 cm(3)). The mean postoperative follow-up time was 35.4 months (range, 3-76 months). Salvage SRS was deemed necessary in seven patients (13.0%). The size of the postoperative tumor remnant was a significant predictor for the necessity of postoperative adjuvant SRS. Normal facial nerve function (House-Brackmann [HB] I) was preserved in 30 patients (57.7%), 17 patients (32.7%) experienced a permanent mild facial nerve deficit (HB II, III), and five patients (9.6%) experienced a severe facial nerve deficit (HB grade IV-VI). CONCLUSIONS: Initial observation after near total surgical removal of VS is a feasible strategy, with only a minority requiring salvage radiosurgery during follow-up.

Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia.

OBJECTIVE: Microvascular decompression (MVD) is considered the method of choice to treat idiopathic trigeminal neuralgia (TN) refractory to medical treatment. However, repeat MVD for recurrent TN is not well established. In this paper, the authors describe a large case series in which patients underwent repeat MVD for recurrent TN, focusing on outcome, risk factors, and complication rates. METHODS: Between 1990 and 2012, a total of 33 consecutive patients underwent repeat MVD for recurrent TN at the University Medical Center Groningen. The authors performed a retrospective chart review and telephone interviews. Risk factors were analyzed by binary logistic regression analysis. RESULTS: After 12 months of follow-up, 22 (67%) operations were successful, of which 19 patients were completely free of pain without medication. With multivariate analysis significant risk factors for success were older age (OR 1.11, p < 0.01) and direct absence of pain after repeat MVD (OR 25.2, p < 0.01). Previous neurodestructive procedures did not influence success rates. Facial numbness occurred in 9 patients (27%), while other morbidity was minimal. There was no mortality. CONCLUSIONS: This study demonstrates that repeat MVD is a feasible therapeutic option with good chances of success, even in patients who have undergone neurodestructive procedures. Complication rates, particularly facial numbness, can be avoided if only a limited neurolysis is performed.

[Treatment of trigeminal neuralgia]. / Behandeling van trigeminusneuralgie.

Classic idiopathic trigeminal neuralgia is characterized by sharp unilateral shooting pain in the distribution of one or more branches of the trigeminal nerve. It involves a diagnosis of exclusion. Initially, therapy consists of medical therapy, preferably with carbamazepine or oxcarbazepine. For patients refractory to medical therapy, microvascular decompression of the trigeminal nerve provides the best long-term outcomes, at a relatively low complication risk. In case of surgical contraindications, there are other options: radiosurgery or a neurodestructive procedure of the trigeminal ganglion. Short-term outcomes after neurodestructive therapy are good, however effects diminish over time. Every patient with idiopathic trigeminal neuralgia in whom medical therapy has failed, should be counselled at an experienced centre in which neurosurgical treatment is available.

Surgery on spinal epidural metastases (SEM) in renal cell carcinoma: a plea for a new paradigm.

BACKGROUND CONTEXT: Prediction models for outcome of decompressive surgical resection of spinal epidural metastases (SEM) have in common that they have been developed for all types of SEM, irrespective of the type of primary tumor. It is our experience in clinical practice, however, that these models often fail to accurately predict outcome in the individual patient. PURPOSE: To investigate whether decision making could be optimized by applying tumor-specific prediction models. For the proof of concept, we analyzed patients with SEM from renal cell carcinoma that we have operated on. STUDY DESIGN/SETTING: Retrospective chart analysis 2006 to 2012. PATIENT SAMPLE: Twenty-one consecutive patients with symptomatic SEM of renal cell carcinoma. OUTCOME MEASURES: Predictive factors for survival. METHODS: Next to established predictive factors for survival, we analyzed the predictive value of the Motzer criteria in these patients. The Motzer criteria comprise a specific and validated risk model for survival in patients with renal cell carcinoma. RESULTS: After multivariable analysis, only Motzer intermediate (hazard ratio [HR] 17.4, 95% confidence interval [CI] 1.82-166, p=.01) and high risk (HR 39.3, 95% CI 3.10-499, p=.005) turned out to be significantly associated with survival in patients with renal cell carcinoma that we have operated on. CONCLUSIONS: In this study, we have demonstrated that decision making could have been optimized by implementing the Motzer criteria next to established prediction models. We, therefore, suggest that in future, in patients with SEM from renal cell carcinoma, the Motzer criteria are also taken into account.