Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Esophageal Neoplasms/pathology* ; Prospective Studies ; Programmed Cell Death 1 Receptor/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Liver Diseases/etiology*

Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Esophageal Neoplasms/pathology* ; Neoadjuvant Therapy ; Carcinoma, Squamous Cell/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Esophagectomy ; Prognosis ; Neoplasm Staging

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/pathology* ; Anaplastic Lymphoma Kinase/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Mutation ; Cytoskeletal Proteins/genetics* ; Lung/pathology* ; Oncogene Proteins, Fusion/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Tumor Suppressor Protein p53/genetics*

Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).
Humans ; Mouth Neoplasms/pathology* ; Carcinoma, Squamous Cell/metabolism* ; Luteolin/therapeutic use* ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; Cell Line, Tumor

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.
Humans ; Esophageal Squamous Cell Carcinoma/surgery* ; Carcinoma, Squamous Cell/pathology* ; Esophageal Neoplasms/pathology* ; Combined Modality Therapy ; Immunotherapy

Objective: To compare the effects of preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the long-term survival of patients with radical resection for esophageal squamous cell carcinoma. Methods: Totally 1 082 patients with stage T3-4aN0-3M0 thoracic esophageal squamous cell carcinoma were recruited in this study who underwent radical resection at Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University from January 2005 to January 2015. There were 798 males and 284 females, with a median age of 61 years (range: 37 to 86 years). There were 138 patients undergoing preoperative neoadjuvant chemotherapy, 392 patients postoperative adjuvant chemotherapy, and 552 patients surgery alone. The neoadjuvant chemotherapy group was used as the benchmark group to match the propensity score with the adjuvant chemotherapy group and the surgery-only group respectively at a ratio of 1∶3. A total of 7 covariates including tumor location, number of positive lymph nodes, tumor invasion depth, tumor differentiation degree, surgical procedure, vascular tumor thrombus and nerve invasion were included, and the caliper value was taken as 0.1. After matching, a total of 699 patients were included for the analysis, including 128 patients in the neoadjuvant chemotherapy group, 267 patients in the adjuvant chemotherapy group, and 304 patients in the surgery alone group. The Kaplan-Meier method was used to generate the survival curves which was tested by the Log-rank method for survival analysis. Results: After matching analysis, the 5-year overall survival rate was 41.5% in the neoadjuvant chemotherapy group with a median overall survival time of 43 months (95%CI: 27 to 59 months), 57.6% in the adjuvant chemotherapy group with a median overall survival time unreached, and 24.9% in the surgery alone group with a median overall survival time of 28 months (95%CI: 25 to 31 months) (χ²=60.475, P<0.01). For overall survival after matching, the adjuvant chemotherapy group was better than the neoadjuvant chemotherapy group (χ²=11.384, P=0.001), the neoadjuvant chemotherapy group was better than the surgery alone group (χ²=8.654, P=0.003), and the adjuvant chemotherapy group was better than surgery alone group (χ²=60.234, P<0.01). Conclusion: Both preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy can improve the long-term survival of patients with locally advanced esophageal squamous cell carcinoma undergoing radical resection, and the improvement effect of postoperative adjuvant chemotherapy is more obvious.
Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Esophageal Neoplasms/pathology* ; Esophageal Squamous Cell Carcinoma ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Propensity Score ; Retrospective Studies ; Survival Rate

BACKGROUND: Immune checkpoint inhibitors (ICIs) improved survival of partial patients with lung squamous cell carcinoma (LUSC). However, it was still insufficient of data in older patients. This study aimed to investigate the efficacy and toxicity of immunotherapy in patients with LUSC in Chinese population of real world. METHODS: A total of 185 LUSC patients underwent pathological diagnosis were involved from January 2018 to January 2022. Patients were divided into elderly group (age ≥70 years) and younger group (age <70 years). The efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line treatment was compared. The expression of programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB) were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to evaluate the efficacy, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to evaluate immune-related adverse. Kaplan-Meier and Log-rank test was performed. Cox regression was used in prognostic analysis. RESULTS: Combined therapy acquired significantly higher overall response rate (ORR) compared with chemotherapy alone in elderly group (P<0.05), and also in younger group, despite the difference was not significant (P>0.05). The median progression-free survival (mPFS) and median overall survival (mOS) in elderly group were similar with younger group (P>0.05). Both combined group and immunology alone demonstrated prolonged mPFS in first-line compared with chemotherapy in elderly group. And combined group demonstrated significantly prolonged mPFS compared with chemotherapy in younger group (P<0.01). There was no difference of mOS between different regimes in two groups. Elderly LUSC patients had higher PD-L1 positive rate (≥1%) and similar TMB compared with younger group. There was no relationship between mPFS and mOS with the expression of PD-L1 and TMB. Immunology combined with chemotherapy demonstrated better mPFS compared to chemotherapy in first-line therapy with TMB-High (P<0.05), and inferior mPFS with TMB-Low despite the difference was not significant (P>0.05). Cox regression model demonstrated that clinical stage was an independent predictor and prognostic factor. The incidence of immune-related adverse was 58.0% (51/88) and grade 3 or above 25.0% (22/88). The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue. CONCLUSIONS Immunology combined with chemotherapy increased ORR, mPFS and mOS of Chinese patients with LUSC in first-line therapy compared with chemotherapy. There was no difference of efficacy and adverse effects rate between elderly group and younger group. The adverse effects of immunology in elderly patients with LUSC were controllable.
Aged ; B7-H1 Antigen/analysis* ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung/pathology* ; Carcinoma, Squamous Cell/drug therapy* ; China ; Humans ; Lung/pathology* ; Lung Neoplasms/pathology*

Humans ; Squamous Cell Carcinoma of Head and Neck ; Neoadjuvant Therapy ; Head and Neck Neoplasms ; Carcinoma, Squamous Cell/pathology* ; Immunotherapy

Immune checkpoint inhibitors (ICIs) present significant efficacy in the treatment of malignant tumors, and they have been approved as the first-line of treatment for various cancers. Pembrolizumab monotherapy or combined with chemotherapy has been recommended by domestic and foreign guidelines for the first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma. Although ICIs represent a milestone in the treatment of head and neck squamous cell carcinoma, potential problems still need to be addressed, such as the selection of the efficacy predictors for ICIs, the evaluation of the tumor response to ICIs, and the treatment of immune hyperprogression and immune-related adverse events. Therefore, to form a relatively unified understanding of ICIs treatment for head and neck squamous cell carcinoma, we integrated the clinical experience of multi-disciplinary experts of head and neck cancers on the basis of current clinical hot issues and finally developed this consensus.
Humans ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Immune Checkpoint Inhibitors ; Consensus ; Neoplasm Recurrence, Local/pathology* ; Head and Neck Neoplasms/drug therapy*

Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8⁺ T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/pathology* ; Carcinoma, Adenoid Cystic/pathology* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Humans ; Immunosuppression Therapy ; Interferon-gamma/pharmacology* ; Mouth Neoplasms/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Salivary Gland Neoplasms/pathology*