Background Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack of reliable metabolic biomarkers to predict irAEs. This study aims to explore the potential metabolic biomarkers to predict risk of irAEs and to investigate the association of plasma metabolites level with survival in patients with lung cancer receiving PD-1/PD-L1 inhibitor treatment. Methods The study collected 170 plasmas of 85 patients with lung cancer who received immune checkpoint inhibitors (ICIs) treatment. 58 plasma samples of 29 patients with irAEs were collected before ICIs treatment and at the onset of irAEs. 112 plasma samples of 56 patients who did not develop irAEs were collected before ICIs treatment and plasma matched by treatment cycles to onset of irAEs patients. Untargeted metabolomics analysis was used to identify the differential metabolites before initiating ICIs treatment and during the process that development of irAEs. Kaplan-Meier curves analysis was used to detect the associations of plasma metabolites level with survival of patients with lung cancer. Results A total of 24 differential metabolites were identified to predict the occurrence of irAEs. Baseline acylcarnitines and steroids levels are significantly higher in patients with irAEs, and the model of eight acylcarnitine and six steroid metabolites baseline level predicts irAEs occurrence with area under the curve of 0.91. Patients with lower concentration of baseline decenoylcarnitine(AcCa(10:1) 2, decenoylcarnitine(AcCa(10:1) 3 and hexanoylcarnitine(AcCa(6:0) in plasma would have better overall survival (OS). Moreover, 52 differential metabolites were identified related to irAEs during ICIs treatment, dehydroepiandrosterone sulfate, corticoserone, cortisol, thyroxine and sphinganine 1-phaosphate were significantly decreased in irAEs group while oxoglutaric acid and taurocholic acid were significantly increased in irAEs group. Conclusions High levels of acylcarnitines and steroid hormone metabolites might be risk factor to development of irAEs, and levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3 and hexanoylcarnitine (AcCa(6:0) could be used to predict OS for patients with lung cancer received ICIs treatment.

Purpose: The purpose of this study was to retrospectively analyze the safety and clinical efficacy of anlotinib combined with dose-dense temozolomide (TMZ) as the first-line therapy in the treatment of recurrent glioblastoma (rGBM).Patients and Methods: We collected the clinical data of 20 patients with rGBM. All patients received anlotinib (12 mg daily, orally for 2 weeks, discontinued for 1 week, repeated every 3 weeks) combined with dose-dense TMZ (100 mg/m², 7 days on with 7 days off) until the disease progressed (PD) or adverse effects (AEs) above grade 4 appeared. Grade 3 AEs need to be restored to grade 2 before continuing treatment, and the daily dose of anlotinib is reduced to 10 mg. The patients were reexamined by head magnetic resonance imaging (MRI) every 1 to 3 months. The therapeutic effect was evaluated according to Response Assessment in Neuro-Oncology (RANO) criteria. The survival rate was analyzed by Kaplan-Meier survival curve analysis. The baseline of all survival index statistics was the start of anlotinib combined with dose-dense of TMZ. National Cancer Institute-Common Terminology Criteria Adverse Events version 4.0 (NCI-CTCAE 4.0) was used to evaluate AEs.Results: Twenty cases of rGBM were evaluated according to the RANO criteria after treatment with anlotinib and dose-dense TMZ, including five cases of stable disease (SD), thirteen cases of partial response (PR), one case of complete response (CR), and one case of PD. The median follow-up time was 13.4 (95% CI, 10.5–16.3) months. The 1-year overall survival (OS) rate was 47.7%. The 6-month progression-free survival (PFS) rate was 55%. In the IDH wild type group, the median PFS and median OS were 6.1 and 11.9 months, respectively. We observed that AEs associated with treatment were tolerable. One patient stopped taking the drug because of cerebral infarction. There were no treatment-related deaths.Conclusion: Anlotinib combined with dose-dense TMZ for the first-line therapy showed good efficacy in OS, PFS, ORR, and DCR in the treatment of rGBM, and the AEs were tolerant. Randomized controlled clinical trials investigating the treatment of rGBM with anlotinib are necessary.

Objective: This study aimed to observe the range of exposure, indications, and feasibility of the retromastoid keyhole approach via grinding partial petrous ridge to the middle fossa. Methods: Simulated endoscopic surgeries via grinding suprameatal tubercle and petrous ridge to expose the middle fossa in retromastoid keyhole approach were performed on 8 adult cadaver heads (16 sides) fixed by formalin. The maximum exposure range in endoscope was observed. The boundaries of Parkinson triangle and the anatomic structures contained by Meckel cave and cavernous sinus (CS) lateral wall were revealed. The distances from midpoint of sigmoid sinus posterior border to every important anatomic structures in the middle fossa and the length of all sides of Parkinson triangle were measured. Results: By using endoscope, the exposure of the cerebellopontine angle, ventrolateral brainstem, incisure of tentorium, petroclival region, and CS lateral wall were satisfactory. Many important anatomic structures in middle fossa were exposed well. The distances from midpoint of posterior border of sigmoid sinus to suprameatal tubercle, trigeminal semilunar ganglion, posterior curve segment of internal carotid artery were 34.42 ± 2.14, 54.52 ± 2.87, and 65.15 ± 3.13 mm. The lengths of all sides of Parkinson triangle were 18.97 ± 2.93, 16.23 ± 2.02, and 8.04 ± 2.34 mm. Conclusion: The retromastoid keyhole approach via grinding partial petrous ridge to the middle fossa by using endoscope can increase the exposure of middle fossa effectively, which is proper for most lesions in posterior cranial fossa while some parts extend to middle fossa.