ABSTRACT
BRAF and MEK inhibition is efficient in patients with BRAF V600-mutated metastatic melanoma, but due to acquired resistance the duration of response (DoR) is often only short-lived. In this retrospective multicenter study with 60 patients suffering from inoperable or metastatic melanoma we evaluated the efficacy of re-challenge with a BRAF inhibitor (BRAF2) with or without MEK-inhibition after progressive disease upon previous treatment with a BRAF inhibitor (BRAF1) with or without MEK inhibition. Treatment with BRAF1 led to a disease control rate (DCR) of 90% with 12% complete responses (CR), 58% partial responses (PR) and 20% stable diseases (SD), the median progression-free survival (PFS) was 9.9 and DoR 10.7 months. BRAF2 with (68%) or without (32%) additional MEK inhibition was initiated after a median interval of 3.4 months. DCR after re-challenge with BRAF2 was 57%, 8% CR, 20% PR and 28% SD, median PFS was 5.0 and DoR 14.0 months. The duration of the treatment interval or the treatment in the interval did not influence the DCR or PFS to BRAF2. The only predictive factor for response to BRAF2 was previous response to BRAF1; all patients with CR to BRAF1 achieved disease control with BRAF2, but only 60% of the patients with PR to BRAF1 (p=0.002). Addition of MEK inhibition to BRAF2 after treatment with BRAF1 as monotherapy did not significantly increase the DCR or PFS compared to patients treated solely with mono- or combination therapy. In conclusion re-challenge with a BRAF inhibitor is a meaningful therapeutic option for patients with BRAF V600-mutated metastatic melanoma.
ABSTRACT
BACKGROUND: To date, there is growing consensus that PEEK material may be used for interbody fusion in spinal infections. Data supporting that claim are however restricted to a few very small clinical series. The aim of this study is to evaluate the outcome of surgical treatment of pyogenic spinal infections with PEEK cages in combination with posterior pedicel screw fixation. METHODS: Between 2006 and 2013, a total of 211 patients suffering from spondylodiscitis underwent surgical debridement and instrumentation. There were 52 cases where PEEK cages were used. Laboratory and physical examinations were assessed at a 3-month follow-up. Last follow-up was performed with at a minimum of 12 months after surgery via a telephone interview. RESULTS: Mean age at presentation was 67 years, with 19 (37 %) male patients and 33 (63 %) female. Distribution of the infection was lumbar in 29 (56 %%), thoracic in 3 (6 %) and cervical in 11 (21 %) cases. Nine patients (17 %) had concomitant non-contiguous spondylodiscitis. Epidural abscess was found in 17 patients (33 %); 48 (92 %%) had pain; neurological deficits were found in 20 patients (38 %). All patients in this series underwent surgical debridement with instrumentation of the spine. Postoperative intravenous antibiotics were administered for 15.4 ± 6.8 days followed by 2.9 ± 0.5 months of oral antibiotics. Complete resolution of the infection was achieved in all cases. Of the 28 patients with neurological deficits, 6 had full recovery and 10 had improved incompletely after surgery. One patient suffered from a pulmonary embolism postoperatively. There were no mortalities. CONCLUSIONS: Use of PEEK cages for interbody fusion is feasible and safe in patients suffering from a pyogenic spinal infection.
