Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

PD-L1 expression with respect to driver mutations in non-small cell lung cancer in an Asian population: a large study of 1370 cases in China.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression with respect to genetic alternations has not been well established in non-small cell lung cancer (NSCLC), especially in the Asian population. METHODS: We reviewed 1370 NSCLC patients from a prospectively maintained database. Immunohistochemistry was performed on tumor cells and tumor-infiltrating lymphocytes (TILs) using the VENTANA (SP142) anti-PD-L1 antibody. The tumor proportion score (TPS) cutoff values were set at ⩾1% and ⩾50%, and the immune proportion score (IPS) cutoff values were set at ⩾1% and ⩾10%. RESULTS: In tumor cells, PD-L1 positivity was observed in 405 (29.6%), 122 (8.9%), and 27 (2.0%) patients with TPS cutoff values at ⩾1% and ⩾50%. Contrastingly, TILs of 1154 (84.2%) and 346 (25.3%) patients stained positive at IPS cutoff values of ⩾1% and ⩾50%, respectively. PD-L1 expression was more common in patients who were mutation-negative irrespective of the TPS cutoff values and tumor size. PD-L1 expression in tumor cells was less frequent in patients harboring EGFR mutations (18.8% TPS ⩾ 1% and 4.6% TPS ⩾ 50%). Conversely, PD-L1 expression was high in the presence of KRAS mutations (47.3% TPS ⩾ 1% and 22.5% TPS ⩾ 50%). Overall, KRAS, BRAF, PICK3A, MET mutations and ROS1 and RET translocations were more frequent, while EGFR and HER2 mutations and ALK translocations were less frequent compared with the overall PD-L1 expression levels. Although the difference between TILs among the PD-L1-positive cases was comparatively small, PD-L1 positivity was less prevalent in EGFR-mutated tumors and more common in those with KRAS mutations, ROS1 translocations, BRAF mutations, or MET mutations. CONCLUSION: Our study showed the heterogeneity in PD-L1 expression with respect to nine major oncogenic drivers in China. Future studies are warranted to further clarify the association between PD-L1 expression and driver mutations in NSCLC.

Structural characterization of a tetrapeptide from Sesame flavor-type Baijiu and its interactions with aroma compounds.

The small molecules in Chinese Baijiu have been widely reported, but there is little information on peptides since their low concentrations. A tetrapeptide, Asp-Arg-Ala-Arg (DRAR), was newly identified from Jingzhi Sesame flavor-type Baijiu (SFTB) by high-performance liquid chromatography and quadrupole-time-of-flight-mass spectrometry (HPLC-Q-TOF-MS) with a concentration of 13.159 ±â€¯0.202 µg/L (P > 0.05). Interactions between DRAR and volatile compounds were characterized using headspace solid-phase micro-extraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS), and the results indicated that DRAR could suppress the volatility of aroma compounds by 0.09-39.02 %, especially with respect to esters and alcohols. The involved binding modes of DRAR with esters or alcohols in 46% ethanol/water solutions (v/v) were respectively determined by ultraviolet (UV) absorption spectroscopy. According to the Van't Hoff equation, the thermodynamic parameters (for DRAR - esters complex, ΔH = -34.7 KJ mol-1, ΔS = -66.4 J mol-1 K-1 and for DRAR - alcohols complex, ΔH = -40.8 KJ mol-1, ΔS = -91.8 J mol-1 K-1) indicated that hydrogen bonds and van der Waals forces played major roles in stabilizing the DRAR-esters and DRAR-alcohols complexes. This study will help us to further understand the interaction mechanisms between aroma compounds and peptides, and the important role of peptides on the quality of Chinese Baijiu.