Objective: Neoadjuvant chemotherapy regimens have shown encouraging efficacy characterized by high objective response rate (ORR), pathologic complete response (pCR) rate, and major pathologic response (MPR) rate, alongside acceptable safety. This single-center retrospective study aimed to evaluate the safety and efficacy of neoadjuvant pembrolizumab plus chemotherapy in patients with locally advanced resectable oral and oropharyngeal squamous cell carcinomas (LA-OSCC/OPSCC). Materials and methods: A total of 50 patients were included. The patients received 2-4 cycles of neoadjuvant therapy with pembrolizumab, albumin-bound paclitaxel and cisplatin before surgery, followed by adjuvant radiotherapy or immunotherapy. Results: The median follow-up time was 31.7 months (95%CI, 29.4-34.0). The ORR was 85.4%, and the MPR rate was 65.8%. The 1-year event-free survival (EFS) rate was 88.8% (95%CI, 79.8%-98.8%). Patients with moderate programmed cell death ligand 1 (PD-L1) expression (combined positive score (CPS) 1 to <10) achieved the highest MPR rate (71.4%), underscoring the potential predictive value of PD-L1 expression. Treatment-related adverse events (TRAEs), most commonly alopecia, anemia, neutropenia, and nausea, were manageable. No treatment-related deaths occurred. Conclusion: This retrospective analysis indicates that neoadjuvant pembrolizumab combined with chemotherapy is a promising strategy for patients with LA-OSCC/OPSCC. Future prospective studies with larger cohorts and longer follow-up are warranted to confirm these findings.

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is characterised by hyperactivation of the cyclin-dependent kinase 4/6 (CDK4/6) pathway. As immunotherapy has become the first-line treatment for HNSCC, resistance to anti-programmed death-1 (PD-1) agents has emerged as a pivotal challenge. This prospective, single arm, phase II study (NCT05721443) evaluated the efficacy and safety of dalpiciclib, a CDK4/6 inhibitor, combined with cetuximab in patients with anti-PD-1-resistant, HPV-negative recurrent and/or metastatic HNSCC. Patients diagnosed with p16-negative R/M HNSCC resistant to first-line anti-PD-1 therapy without prior cetuximab treatment were enroled. Patients received oral dalpiciclib (150 mg daily on days 1-21 of each 28-day cycle) and intravenous cetuximab (400 mg/m2 on day 1 of cycle 1, followed by 250 mg/m2 weekly in each cycle). The primary endpoint was objective response rate (ORR), secondary endpoints were overall survival, progression-free survival, duration of response, and safety. Between March 2023 and November 2024, a total of 28 patients were enroled. The ORR was 67.9

INTRODUCTION:Oral mucosal melanoma (OMM) is a rare subtype of melanoma but exhibits highly invasive biological behavior. Programmed cell death protein 1 (PD-1) monotherapy showed lower response in OMM than other subtypes of melanoma. MATERIALS AND METHODS:We retrospectively analyzed the efficacy and safety of pembrolizumab with anlotinib in patients with advanced OMM between August 2018 and September 2024. The primary endpoint was objective response rate (ORR); the secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). RESULTS:Forty-one patients were enrolled in our study. Seventeen patients (41.4%) achieved an objective response. The median PFS was 6.4 months (95% confidence interval [CI], 4.5-8.3 months), and the median OS was 10.0 months (95% CI, 8.3-11.7 months). Thirty-three patients (80.5%) experienced at least one TRAE. The most common TRAEs were hypertension (29.3%), hand-foot syndrome (19.5%), and anemia (19.5%). Grade 3 or higher TRAEs occurred in two patients (4.8%), and no grade 5 TRAEs were observed. CONCLUSIONS:Our study suggested that pembrolizumab with anlotinib in patients with advanced OMM showed potential efficacy and manageable adverse effects. Further studies are needed to confirm the efficacy of this combination strategy.

e18005 Background: Targeting vascular endothelial growth factor receptor (VEGFR) may synergistically enhance the antitumor effects of immune checkpoint inhibitors (ICIs). This study evaluated the efficacy and safety of camrelizumab with chemotherapy (Arm A) or apatinib (Arm B) as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Methods: This open-label, double-cohort, multicenter, phase II study (NCT05156970) enrolled patients with recurrent or metastatic HNSCC who had not received prior systemic therapy for metastatic or recurrent disease. In Arm A, patients received camrelizumab (200 mg intravenous, day 1), followed by docetaxel (75 mg/m²) and cisplatin (75 mg/m²) or carboplatin (area under the curve 5) on day 2 every 3 weeks for up to six cycles, followed by camrelizumab monotherapy (200 mg intravenous, day 1, every 3 weeks). In Arm B, patients received camrelizumab (200 mg intravenous, day 1, every 3 weeks) plus oral apatinib (250 mg daily). The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and safety. Results: Between July 2021 and May 2024, 81 patients were enrolled (41 in Arm A and 40 in Arm B). The median follow-up was 11.93 months. The median OS was 16.40 months (95% confidence interval [CI], 4.13-28.67) in Arm A and 21.00 months (95% CI, 16.63-25.37) in Arm B. The median PFS was 4.57 months (95% CI, 1.11-8.03) in Arm A and 4.20 months (95% CI, 0.00-8.54) in Arm B. The ORR was 46.3% (95% CI, 32.0%-61.0%) in Arm A and 50.0% (95% CI, 35.0%-65.0%) in Arm B. Grade 3 or higher treatment-related adverse events occurred in six patients (14.6%) in Arm A and seven (17.5%) in Arm B. Conclusions: Camrelizumab combined with chemotherapy or apatinib demonstrated encouraging survival outcomes, with a favorable safety profile. These findings support further investigation of camrelizumab-based regimens as first-line treatments for patients with recurrent or metastatic HNSCC. Clinical trial information: NCT05156970 .

Cryoablation therapy for tumors has a long history of clinical application. Its anti-tumor mechanisms and histopathological changes have been well established, with extensive clinical practice demonstrating its safety and efficacy, theoretically making it an ideal modality for tumor treatment. Historically constrained by limitations in cryogenic media and freezing equipment, its therapeutic effectiveness and clinical adoption were significantly restricted. The emergence of new-generation cryoablation systems represented by Argon-Helium cryosurgical systems has achieved substantial advancements in refrigeration efficiency, ablation range precision, and temperature monitoring accuracy, thereby greatly promoting the widespread adoption of tumor cryoablation technology. This consensus systematically summarizes the mechanisms of cryoablation technology, indications for cryotherapy in head and neck mucosal melanoma, standardized clinical treatment protocols, management of adverse reactions, and related principles. It aims to provide authoritative references for standardizing cryoablation therapy in the treatment of head and neck mucosal melanoma.

6026 Background: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is characterized by hyperactivation of the cyclin-dependent kinase 4/6 (CDK4/6) pathway. As immunotherapy has become the first-line treatment for HNSCC, resistance to anti-programmed death-1 (PD-1) agents has emerged as a pivotal challenge. This phase II study evaluated the efficacy and safety of dalpiciclib, a CDK4/6 inhibitor, combined with cetuximab in patients with anti-PD-1-resistant, HPV-negative recurrent or metastatic (R/M) HNSCC. Methods: Patients diagnosed with p16-negative R/M HNSCC resistant to first-line anti-PD-1 therapy and cetuximab-naïve were enrolled. Patients received oral dalpiciclib 150 mg daily for 21 consecutive days and intravenous cetuximab (400 mg/m² on day 1 of cycle 1, followed by 250 mg/m² weekly) in 28-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS). Simon's two-stage design was used, with study termination planned if ≤1 response was observed among the first 14 patients. If met, an additional 12 patients were enrolled. Results: A total of 28 patients were enrolled, with a median age of 58 years (range 30-75 years). Among 28 evaluable patients, 3 had disease progression, 6 had stable disease, and 19 achieved partial response. The ORR was 67.9% (95% confidence interval [CI], 49.0%-82.0%), and the disease control rate was 89.3% (95% CI, 72.0%-97.0%). As of December 31, 2024, 9 patients remained on treatment. With a median follow-up of 7.34 months, the median PFS was 5.3 months (95% CI, 1.33-9.27), and the median OS was 17.0 months. Treatment-related adverse events (TRAEs) occurred in all patients, predominantly grade 1-2. The most common TRAEs were neutrophil count decreased (25/28, 89.3%), white blood cell count decreased (25/28, 89.3%), and acneiform rash (16/28, 57.1%). Grade 3 TRAEs included neutrophil count decreased (9/28, 32.1%) and white blood cell count decreased (9/28, 32.1%). No grade 4/5 TRAEs were observed. Conclusions: Dalpiciclib combined with cetuximab was well-tolerated and demonstrated potentially favorable efficacy in patients with anti-PD-1-resistant, HPV-negative R/M HNSCC. Clinical trial information: NCT05721443 .

Mucosal melanoma (MM) is a rare and aggressive form of melanoma with a poorer prognosis compared to other subtypes. Recent large-scale next-generation sequencing studies, including our own research, have demonstrated that the molecular characteristics and potential oncogenic drivers of MM differ significantly from those of cutaneous melanoma. The emergence of selective CDK4/6 inhibitors, already approved for use in breast cancer and undergoing phase III clinical trials for other solid tumors, represents a promising development in the treatment of MM. Recent studies have shown that CDK4/6 inhibitors not only induce cell cycle arrest but also play a crucial role in facilitating the interaction between tumor cells and the host immune system. Moreover, our findings indicate that dysregulation of cell cycle progression due to cyclin‐dependent kinase 4 (CDK4) amplification is a significant genetic characteristic in a substantial portion of MM cases. Targeting CDK4 in specific MM patients shows promise for precision cancer therapy, utilizing molecularly characterized MM patient-derived xenograft (PDX) models and clinical trials. This paper provides an overview of existing literature on CDK4/6 dysregulation in MM, as well as preclinical and clinical investigations on CDK4/6 inhibitors and potential combination therapies for MM treatment.

Abstract Background Mucosal melanoma (MM) is a rare but devastating subtype of melanoma. Our previous studies have demonstrated robust anti-tumor effects of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in head and neck MM (HNMM) patient-derived xenograft models with CDK4 amplification. Herein, we aimed to investigate the efficacy and safety of dalpiciclib (SHR6390), a CDK4/6 inhibitor, in HNMM patients harboring CDK4 amplification. Methods The anti-tumor efficacy of dalpiciclib was assessed by HNMM patient-derived xenograft (PDX) models and patient-derived tumor cells (PDC) in vivo and in vitro. Immunohistochemical analyses and western blot were then performed to assess the markers of cell proliferation and CDK4/6 signaling pathway. For the clinical trial, advanced recurrent and/or metastatic HNMM patients with CDK4 amplification were treated with dalpiciclib 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results Dalpiciclib profoundly suppressed growth of HNMM-PDX and PDC with CDK4 amplification, whereas it showed relatively weak suppression in those with CDK4 wild type compared with vehicle. And dalpiciclib resulted in a remarkable reduction in the expression levels of Ki-67 and phosphorylated Rb compared with control group. In the clinical trial, a total of 17 patients were enrolled, and 16 patients were evaluable. The ORR was 6.3%, and the DCR was 81.3%. The estimated median PFS was 9.9 months (95% CI, 4.8-NA), and the median OS was not reached. The rate of OS at 12 months and 24 months was 68.8% (95% CI, 0.494–0.957) and 51.6% (95% CI, 0.307–0.866), respectively. The most frequent adverse events were neutrophil count decrease, white blood cell count decrease, and fatigue. Conclusions Dalpiciclib was well-tolerated and displayed a durable benefit for HNMM patients with CDK4 amplification in this study. Further studies on CDK4 inhibitors and its combination strategy for MM are worth further exploration. Trial registration ChiCTR2000031608.

BackgroundThe KEYNOTE-048 and KEYNOTE-040 study have demonstrated the efficacy of pembrolizumab in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC), we conducted this real-world study to investigate the efficacy of pembrolizumab in patients with R/M HNSCC.MethodsThis is a single-center retrospective study conducted in the Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Shanghai, China). Between December 2020 and December 2022, a total of 77 patients with R/M HNSCC were included into analysis. The primary endpoint of the study was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), overall response rate (ORR)and toxicity.Efficacy was assessed according to RECIST version 1.1.SPSS 27.0 and GraphPad Prism 8.0 software were utilized to perform the statistical analysis.ResultsBy the cut-off date (February 28, 2023), the median OS,PFS and ORR were 15.97 months,8.53 months and 48.9% in patients treated with the pembrolizumab regimen in the first line therapy. Among these patients, 17 patients received pembrolizumab with cetuximab,and 18 received pembrolizumab with chemotherapy.We observed no significant differences between two groups neither in median OS (13.9 vs 19.4 months, P=0.3582) nor PFS (unreached vs 8.233 months, P= 0.2807). In the ≥2nd line therapy (n=30), the median OS, PFS and ORR were 5.7 months, 2.58 months and 20% respectively. Combined positive score (CPS) was eligible from 54 patients. For first line therapy, the median OS and PFS were 14.6 and 8.53 months in patients with CPS ≥1, and median OS and PFS were 14.6 and 12.33 months in patients with CPS ≥20. The immune-related adverse events (irAEs) were occurred in the 31 patients (31/77, 40.26%), and the most common potential irAEs were hypothyroidism (25.97%), and pneumonitis (7.79%).ConclusionOur real-world results indicated that pembrolizumab regimen is a promising treatment in patients with R/M HNSCC

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402. In this phase 3 trial, first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with anti-PD-1 finotonlimab plus cisplatin plus 5-fluorouracil (C5F) prolonged overall survival compared with placebo plus C5F.

Pembrolizumab with cisplatin and 5-fluorouracil showed survival benefit but relatively high occurrence of treatment-related adverse events (TRAEs) for recurrent/metastatic oral squamous cell carcinoma (R/M OSCC). A more tolerable regime is needed. This trial enrolled 20 R/M OSCC patients with previously untreated and PD-L1 positive. Patients were administered camrelizumab with docetaxel and cisplatin every 3 weeks for six cycles, followed by camrelizumab monotherapy every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was occurrence of grade ≥ 3 TRAEs, secondary endpoints included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). 45% patients experienced grade ≥ 3 TRAEs, which the most common were anemia (15%), stomatitis (15%), and neutropenia (10%). The most common potential immune-related adverse events were reactive cutaneous capillary endothelial proliferation (RCCEP; 60%), hypothyroidism (35%), and pneumonitis (15%). No treatment-related deaths occurred. The median OS, PFS, and ORR was 14.4 months, 5.35 months, and 40.0% respectively. The study also found RCCEP occurrence, lower FOXP3+ cells, and higher density of intratumor tertiary lymphoid structure were associated with improved efficacy. Our data suggest that camrelizumab with docetaxel/cisplatin as first-line therapy was well tolerable and had potentially favorite efficacy in PD-L1-positive patients with R/M OSCC.

BACKGROUND:Mucosal melanoma has characteristically distinct genetic features and typically poor prognosis. The lack of representative mucosal melanoma models, especially cell lines, has hindered translational research on this melanoma subtype. In this study, we aimed to establish and provide the biological properties, genomic features and the pharmacological profiles of a mucosal melanoma cell line that would contribute to the understanding and treatment optimization of molecularly-defined mucosal melanoma subtype. METHODS:The sample was collected from a 67-year-old mucosal melanoma patient and processed into pieces for the establishment of cell line and patient-derived xenograft (PDX) model. The proliferation and tumorigenic property of cancer cells from different passages were evaluated, and whole-genome sequencing (WGS) was performed on the original tumor, PDX, established cell line, and the matched blood to confirm the establishment and define the genomic features of this cell line. AmpliconArchitect was conducted to depict the architecture of amplified regions detected by WGS. High-throughput drug screening (HTDS) assay including a total of 103 therapeutic agents was implemented on the established cell line, and selected candidate agents were validated in the corresponding PDX model. RESULTS:A mucosal melanoma cell line, MM9H-1, was established which exhibited robust proliferation and tumorigenicity after more than 100 serial passages. Genomic analysis of MM9H-1, corresponding PDX, and the original tumor showed genetic fidelity across genomes, and MM9H-1 was defined as a triple wild-type (TWT) melanoma subtype lacking well-characterized "driver mutations". Instead, the amplification of several oncogenes, telomerase reverse transcriptase (TERT), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), melanocyte Inducing transcription factor (MITF) and INO80 complex ATPase subunit (INO80), via large-scale genomic rearrangement potentially contributed to oncogenesis of MM9H-1. Moreover, HTDS identified proteasome inhibitors, especially bortezomib, as promising therapeutic candidates for MM9H-1, which was verified in the corresponding PDX model in vivo. CONCLUSIONS:We established and characterized a new mucosal melanoma cell line, MM9H-1, and defined this cell line as a TWT melanoma subtype lacking well-characterized "driver mutations". The MM9H-1 cell line could be adopted as a unique model for the preclinical investigation of mucosal melanoma.

Background and purpose: Oral mucosal malignant melanoma (OMM) is a highly malignant solid tumor with a distant metastasis rate of about 40%. The lung is the most common metastatic site. This study aimed to investigate the characteristics and prognostic analysis of OMM with lung metastasis, in order to find the best treatment mode for OMM with lung metastasis. Methods: The data of the patients with lung metastasis diagnosed in the Ninth People’s Hospital Affiliated to the Medical College of Shanghai Jiao Tong University from January 2017 to January 2021 were retrospectively analyzed. The imaging characteristics of chest computed tomography (CT) were summarized, and Kaplan-Meier method was used for survival analysis. Results: In this study, 88% of patients with OMM were diagnosed with lung metastasis within 2 years after operation, including 22 cases (52%) in the first year and 15 cases (36%) in the second year; 71% of patients showed multiple, round or oval nodules of different sizes on chest CT, and few single metastases (10%). Non-scheduled follow-up (P = 0.009), concurrent local recurrence (P = 0.037), concurrent pleural effusion (P = 0.042) and no immunotherapy (P = 0.000) could significantly reduce the survival time of patients. The response of patients with relapse to programmed death-1 (PD-1) immunotherapy was significantly reduced (P = 0.009), and the median overall survival (OS) of PD-1 single drug was only 10 months. After combination therapy with PD-1 and anti-vascular targeted drugs, the median OS could be increased to about 19 months (P = 0.019). Conclusion: OMM is prone to lung metastasis, and even tiny nodules less than 1cm can be metastatic foci. The metastasis of OMM most often occurs within 1-2 years after operation. Regular follow-up can detect early metastasis and significantly prolong the survival. The efficacy of immunotherapy alone for recurrent and metastatic OMM is also poor, and immunotherapy combined with anti-vascular targeted therapy is required.

Importance:The antibody drug conjugate drug MRG003 comprises an anti-epidermal growth factor receptor (EGFR) humanized immunoglobulin G1 monoclonal antibody that is conjugated with monomethyl auristatin E via a valine-citrulline linker. There is currently insufficient evidence of this drug's safety and efficacy. Objective:To evaluate the safety and maximum tolerated dose of MRG003 in a phase 1a study and investigate the preliminary antitumor activity in EGFR-expressing patients in a phase 1b study. Design, Setting, and Participants:This nonrandomized open-label, single-arm, phase 1, multicenter study of solid tumors was divided into 2 parts, phase 1a dose escalation and phase 1b dose expansion. Patients with advanced or metastatic solid tumors who had failed outcomes from or were not able to receive standard treatment were enrolled in phase 1a without EGFR prescreening. Phase 1b recruited EGFR-positive patients with refractory advanced squamous cell carcinomas of the head and neck (SCCHN), nasopharyngeal carcinoma (NPC), and colorectal cancer (CRC). This study was conducted at 7 Chinese centers between April 11, 2018, and March 29, 2021 (data cutoff date). Data analysis took place between April 2021 and June 2021. Interventions:An intravenous dose of 0.1 to 2.5 mg/kg of MRG003 was administered every 3 weeks during phase 1a. During phase 1b, patients were administered the recommended dose identified in phase 1a. Main Outcomes and Measures:The primary end points were dose-limiting toxic effects in phase 1a and objective response rate in phase 1b. The safety, tolerability, immunogenicity, and pharmacokinetics of MRG003 were assessed. Tumor assessment was evaluated by RECIST 1.1. Results:Twenty-two patients (mean [range] age, 54.5 [32.0-67.0] years; 9 women [41%]) were enrolled in phase 1a and 39 patients (mean [range] age, 50.4 [27.0-75.0] years; 8 women [21%]) in phase 1b. The recommended dose was identified as 2.5 mg/kg. Eighty-nine percent of adverse events (AEs) were associated with MRG003 treatment, and most AEs were grade 1 to 2. Nineteen patients (31%) reported grade 3 or greater treatment-related AEs, including hyponatremia, leukocytopenia, neutropenia, increased aspartate aminotransferase levels, and febrile neutropenia. In phase 1a, 1 patient (5%) achieved a partial response, and 5 (23%) achieved stable disease. In phase 1b, 8 patients (21%) achieved a confirmed partial response, and 12 (31%) achieved stable disease. The objective response rates for SCCHN, NPC, and CRC were 40%, 44%, and 0%, and the disease control rates were 100%, 89%, and 25%, respectively. Conclusions and Relevance:The findings of this nonrandomized clinical trial suggest that MRG003 showed a manageable safety profile and promising antitumor activity in patients with EGFR-positive NPC and SCCHN. Trial Registration:Clinicaltrials.gov Identifier: NCT04868344.

Adjuvant therapy plays a critical role in the treatment of oral mucosal melanoma (OMM). Anti-programmed cell death-1 (PD-1) agents are recommended as front-line therapy for metastatic melanoma, but their efficacy as adjuvant therapy for high-risk OMM remains unclear. A single-center, retrospective cohort study was conducted in 193 nodular-type oral mucosal melanoma (NOMM) patients who received chemotherapy alone or in combination with high-dose interferon-α2b (HDI) or anti-PD-1 agents as adjuvant therapy. Multivariate analysis was performed to identify significant prognostic factors for the 2-year overall survival (OS) and progression-free survival (PFS). Tumor thickness, ulceration and invasion level were found to be independent prognostic factors for both 2-year OS and PFS, while T-stage was only associated with OS. The 2-year OS and PFS were 43.5

目的:比较2种活检方法在口腔黏膜恶性黑色素瘤(oral mucosal melanoma,OMM)中的预后差异,以期找到OMM最佳的活检模式.方法:回顾分析2010年1月—2018年1月于上海交通大学医学院附属第九人民医院确诊的OMM病例,比较2种活检方法与预后的关系.主要观察指标为生存期(overall survival,OS),即病理确诊到死亡日期或随访时间节点(2021年9月1日).采用SAS 9.3软件包进行统计学分析.结果:单因素分析显示,T分期、颈淋巴结(CLN)状况、活检类型与OS有统计学相关性.所有3个变量均纳入Cox回归模型中进行多因素分析,结果显示,T分期、颈部淋巴结转移以及活检方法与预后有显著相关性.冷冻活检组颈部淋巴结和远处转移的发生率均显著低于切取活检组(53％:74％和22％:42％,Log-rank=12.955,PP＜0.01);冷冻活检组的3年和5年OS显著高于切取活检组(65％:42％,Log-rank=12.570,P＜0.01;54％:20％,Log-rank=7.203,P＜0.01).结论:冷冻活检组3年及5年OS显著优于切取活检组,冷冻下活检较常规切取活检能显著降低OMM的颈淋巴结及远处转移率.推荐采用冷冻下活检,用以明确OMM的诊断.

目的:探讨针对EGFR靶点的药物(厄洛替尼、尼妥珠单抗)是否影响实验动物的痛阈并初步分析其机制.方法:正常小鼠分为2组(生理盐水,n=6;厄洛替尼,n=6),给药后1 h采用Von Frey纤维丝法、热板法、5％(中性)甲醛致痛实验比较2组动物的痛阈差异.选取正常裸鼠分为3组(Sham组+NS组,n=10;足底成瘤+NS组,n=10;足底成瘤+尼妥珠单抗组,n=10),分别检测造模前1 d,造模后1、5、7、10、14d小鼠机械痛阈、热痛阈.14d后解剖小鼠足爪,组织匀浆后以ELISA法检测IL-1β、IL-6等细胞因子浓度.采用Graphpad Prism软件包处理数据.结果:注射厄洛替尼后,小鼠机械痛阈、热痛阈无明显变化.注射5％(中性)甲醛后,小鼠前相(0～10min,P＜0.01)、后相(10～60min,P＜0.01)舔咬时间显著减少.裸鼠足底成瘤后可诱发小鼠热痛敏、机械痛敏,尼妥珠单抗可提高成瘤小鼠的热痛阈(P＜0.05)及机械痛阈值(P＜0.05).ELISA分析显示,尼妥珠单抗治疗组小鼠足爪组织中IL-1β、IL-6浓度较PBS治疗组显著降低(P＜0.05).结论:厄洛替尼可降低5％甲醛引发的小鼠疼痛;尼妥珠单抗可减少足底成瘤引发的机械痛敏和热痛敏,其机制可能与局部组织中炎性细胞因子降低有关.EGFR靶向药物或可成为晚期癌痛患者良好的镇痛药物之一.

针对数字化单点渐进成型过程的板料回弹问题,建立标准回弹验证模型,并以内角间距尺寸作为评价标准,找到影响回弹特性的四大工艺参数,运用六西格玛设计思维使用正交方法优化试验,通过信号噪声比分析,找到回弹特性最优的工艺参数卡片.回弹特性最优参数工艺包为最大层间距1.2 mm,单向等高路径成型轨迹,进给速度选择最大速度模式8000 mm/min.使用优化后的参数包发现,回弹量从5 mm降低至1 mm,回弹率从1.9％降低至0.5％,回弹量降低了4 mm,效果明显.

Key Points Question What is the safety and antitumor activity of MRG003 in patients with advanced solid tumors? Findings In this phase 1 clinical trial of 61 patients with advanced or metastatic solid tumors, treatment with MRG003 exhibited manageable safety and showed encouraging antitumor activity in squamous cell carcinomas of the head and neck and nasopharyngeal carcinoma, with a confirmed objective response rates of 40% and 44%, respectively. Meaning The study findings suggest the safety of treatment with MRG003 and an acceptable tolerance in most patients with epidermal growth factor receptor–expressing solid tumors, as well as encouraging antitumor activity in patients with squamous cell carcinomas of the head and neck and nasopharyngeal carcinoma.

Background Hyperthermia has been reported to cause cancer stage regression, thus providing surgical opportunities in patients with unresectable tumors and improving the quality of life of patients by preserving certain organs. Methods A prospective open-label phase II trial was conducted to evaluate the efficacy of hyperthermia combined with induction chemotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). Patients received hyperthermia combined with two cycles of 5-fluorouracil, cisplatin, and docetaxel (TPF) induction chemotherapy regimens or TPF induction chemotherapy alone, followed by radical surgery with postoperative radiotherapy. The primary endpoint was the clinical response rate of the induction chemotherapy. The secondary endpoints were overall survival (OS), disease-free survival (DFS), and toxicity. Results A total of 120 patients were enrolled, and 115 patients were included in the clinical response analysis. The clinical response rate was significantly higher in the experimental arm than in the control arm (65.45% vs. 40.00%, p = 0.0088). There were no unexpected toxicities, and hyperthermia and induction chemotherapy did not increase the perioperative morbidity rate. Moreover, there was a significant improvement in DFS, but no significant difference in OS between the two arms. In the subgroup analysis, increased OS and DFS rates were associated with patients with favorable clinical response after induction chemotherapy in the total population, experimental arm, and control arm. Conclusions Our study demonstrates that hyperthermia combined with induction chemotherapy is associated with a high response rate and provides a new treatment option for patients with resectable stage III or IVA OSCC.