Impact of Postoperative Radiotherapy on the Prognosis of Early-Stage (pT1-2N0M0) Oral Tongue Squamous Cell Carcinoma.

PURPOSE: To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS: This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS: Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, P = .003; disease-free survival (DFS), 88% versus 50%, P = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, P = .040; DFS, 87% versus 64%, P = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% v 58%; P = .022; DFS, 76% v 47%; P = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% v 64%; P = .006; 92% v 66%; P = .049) but did not significantly affect OS. CONCLUSION: Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.

Neoantigen load as a prognostic and predictive marker for stage II/III non-small cell lung cancer in Chinese patients.

BACKGROUND: The prognosis for patients with stage II/III non-small cell lung cancer (NSCLC) is unsatisfactory, even after complete tumor resection and adjuvant chemotherapy. Here, we assessed the prognostic and predictive value of immunogenomic signatures for stage II/III NSCLC in Chinese patients. METHODS: A total of 91 paired resected stage II/III NSCLC and normal tissues, including 47 squamous cell lung carcinomas (SCC) and 44 lung adenocarcinomas (ADC), were collected and analyzed using whole exome sequencing (WES) to identify immunogenomic signatures for association with clinicopathological variables and disease-free survival (DFS). RESULTS: Higher neoantigen load (NAL, >2 neoantigens/Mb) exhibited better DFS for SCC patients (p = 0.021) but not ADC patients. A benefit from adjuvant chemotherapy was correlated with lower NAL (≤2 neoantigens/Mb) (p = 0.009). However, tumor mutation burden (TMB), mutations of individual gene, oncogene pathways, and antigen presentation machinery genes, and human leukocyte antigen (HLA)-I number and HLA-I loss of heterozygosity (LOH) had no prognostic or predictive value for DFS of SCC or ADC patients. CONCLUSIONS: NAL is a useful biomarker for lung SCC prognosis and prediction of chemotherapy responses in Chinese patients. The predictive value of NAL for adjuvant immunotherapy should be further explored in patients with resected NSCLC.

Diosgenin inhibits tumor angiogenesis through regulating GRP78-mediated HIF-1α and VEGF/VEGFR signaling pathways.

The present paper describes the molecular mechanism of diosgenin on tumor microenvironment angiogenesis and the regulation of GRP78 in angiogenesis signaling pathway. CCK8 method was used to evaluate the effect of different concentrations of diosgenin on HUVEC activity in hypoxic microenvironment. Apoptosis was detected by Annexin V/PI staining. Tube Formation experiment was conducted to evaluate angiogenesis. Western Blot assay was applied to detect the expressions and phosphorylation levels of the angiogenesis-related pathways HIF-1α, GRP78, VEGF/VEGFR, PI3K/AKT, ERK, and FAK in rheumatoid HUVEC. Silencing GRP78 by siRNA interference technology was employed to investigate the mechanism of GRP78 involved in the regulation of angiogenesis. The results indicated that diosgenin can significantly inhibit the cell viability of hypoxic HUVEC and the significance is dependent on drug concentration. As the concentration increases, HUVEC activity decreases. Cell apoptosis is induced in a dose-dependent manner and angiogenesis can be significantly inhibited. The hypoxic microenvironment can significantly increase the expressions of HIF-lα, GRP78, VEGF/VEGFR, PI3K/AKT, ERK, FAK proteins in angiogenesis-related pathways, and can also enhance the phosphorylation of AKT, ERK1/2 and FAK proteins, which can be decreased by drug intervention. After silencing GRP78, the angiogenesis-related pathway proteins HIF-lα and VEGF/VEGFR are significantly reduced, thus inhibiting the activation of AKT, ERK1/2, and FAK. The anti-tumor angiogenesis mechanism of diosgenin inhibiting the expression of HIF-lα, GRP78, VEGF/VEGFR, PI3K/AKT, ERK1/2 and FAK signaling pathways may be through multiple pathways and targets, and GRP78 is involved in the regulation of angiogenesis signaling pathway.

Metastases to the thyroid gland: A retrospective analysis of 21 patients.

BACKGROUND: Metastases to the thyroid gland are uncommon and often occur in patients with advanced metastatic diseases. The management and prognosis of secondary thyroid malignancies (STMs) are not well established. This retrospective study reported the incidence, clinical characteristics, treatment, and prognosis of STM in patients with metastatic tumors. SUBJECTS AND METHODS: A total of 21 cases (1.2% incidence) diagnosed by fine-needle aspiration between January 2006 to December 2014 in a single center were reviewed. Survival analysis was made by Kaplan-Meier method. RESULTS: The primary malignancies included esophagus cancer (7/21, 33.33%), breast cancer (6/21, 28.57%), head and neck cancer (3/21, 14.29%), unknown primary cancer (3/21, 14.29%), and lung cancer (2/21, 9.52%). The mean overall survival (OS) from diagnosis of primary malignancies was 57.26 months (95% confidence interval [CI]: 31.19-83.34) and the 2-year OS rate was 61.9%, and the mean OS from diagnosis of thyroid metastases was 31.20 months (95% CI: 12.23-50.18) and the 2-year OS rate was 34.3%. Patients with the head and neck cancer and breast cancer had better survival than other patients (from diagnosis of primary malignancies, P < 0.001; from diagnosis of thyroid metastases, P = 0.03). Histological types were also related to OS (from diagnosis of primary malignancies, P = 0.039; from diagnosis of thyroid metastases, P = 0.130). In addition, thyroidectomy may improve OS for patients with isolated metastases. CONCLUSION: The prognosis of STMs basically depends on the anatomic sites and histological types of primary cancers, and thyroidectomy may be considered for patients with isolated metastases.