Efficacy and Safety of Nimotuzumab in Combination with Radiotherapy or Chemoradiotherapy for Local Advanced Head and Neck Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: The present meta-analysis aimed to evaluate the efficacy and safety of adding nimotuzumab to radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: Prospective randomized controlled studies at EMBASE, PubMed, and the Cochrane Library from January 1, 2010, to October 1, 2022, were searched. Data on the overall survival (OS), progress-free survival (PFS), disease-free survival (DFS), complete response rate (CRR), objective response rate (ORR), and all grade adverse events were collected from the enrolled publications. OS was the primary measurement indicator. Pooled analysis was performed with relative risks (RRs), hazard risks (HRs), and their corresponding 95% confidence intervals (CIs) in the software Stata SE 16.0. RESULTS: Six randomized controlled studies were included in the analysis of the overall pooled effect. As compared to the control group, the nimotuzumab intervention group exhibited improved OS by 21% (pooled HR=0.79,95% CI: 0.64-0.98, P=0.028), along with PFS up to 31% (HR=0.69, 95% CI: 0.55-0.86, P=0.001) and DFS up to 29% (HR=0.71, 95% CI: 0.56-0.91, P=0.006), increased CRR as 50% (RR=1.50, 95%CI:1.09-2.04; P=0.012), and ORR as 35% (RR=1.35, 95%- CI:1.04-1.73; P=0.022). Regarding safety, nimotuzumab in combination with RT or CRT did not increase the incidence of all grade adverse events (pooled-RD=-1.27, 95%CI:-2.78-0.23, P=0.099). CONCLUSION: The present meta-analysis has demonstrated that nimotuzumab, in combination with RT or CRT, could provide survival benefits and increase response rates. Its safety profile has been found to be controllable.

Development and validation of a model to predict the risk of recurrence in patients with laryngeal squamous cell carcinoma after total laryngectomy.

Background: Recurrence is still the main obstacle to the survival of laryngeal squamous cell carcinoma (LSCC) patients who have undergone a total laryngectomy. Previous models for recurrence prediction in patients with LSCC were based on pathological information, while the role of easily accessible inflammatory markers in the prognosis of LSCC patients has rarely been reported. This study sought to develop and validate a model to predict the risk of recurrence in LSCC patients who underwent total laryngectomy. Methods: A total of 204 LSCC patients who underwent a total laryngectomy were included in this retrospective cohort study. Demographics, pathology, and inflammatory markers of patients were collected. All the patients were randomly divided into a training set and a test set at a ratio of 4:1. Patients were followed up for 3 years after surgery or until death occurred during this period. The random-forest method was used to develop a predictive model. The performance of the model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC) with the 95% confidence interval (CI), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Of the 204 LSCC patients, 56 (27.45%) patients had a recurrence. The random-forest prediction model was an all-factor model, and the most important predictors of the model were the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR), with proportions of 0.121, 0.100, and 0.092, respectively. The AUCs of the model in predicting the recurrence of LSCC in the training set and the test set were 0.960 (95% CI, 0.931-0.989) and 0.721 (95% CI, 0.716-0.726), respectively. The sensitivity, specificity, accuracy, PPV, and NPV of the model in the test set were 0.750 (95% CI, 0.505-0.995), 0.690 (95% CI, 0.521-0.858), 0.707 (95% CI, 0.568-0.847), 0.500 (95% CI, 0.269-0.921), and 0.870 (95% CI, 0.732-1.000), respectively. Conclusions: A model to predict the risk of recurrence in LSCC patients who have undergone a total laryngectomy was established, and inflammatory markers AGR, NLR, and PLR play an important role in the predictive model.

MicroRNA-137 Inhibits Esophageal Squamous Cell Carcinoma by Downregulating DAAM1.

BACKGROUND: A growing body of evidence demonstrates that miR-137 acts against cancers; however, the biological function of miR-137 in esophageal squamous cell carcinoma (ESCC) remains to be fully understood. OBJECTIVE: The aim of this study is to explore the role of miR-137 in ESCC. METHODS: miR-137 expression was detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and target protein expression was detected by western blot. Cell counting, colony formation and flow cytometry were employed to determine the effects of miR-137 on the growth of ESCC cells. Dual-luciferase reporter assay was performed to validate the binding of miR- 137 with a dishevelled-associated activator of morphogenesis 1 (DAAM1) 3'-UTR. RESULTS: miR-137 was shown to be down-regulated in ESCC. miR-137 expression was inversely correlated with the 5-year survival rate of ESCC patients. Up-regulated miR-137 attenuated ESCC proliferation and promoted ESCC cell apoptosis. Meanwhile, to further reveal how miR-137 regulated the malignant behaviors of ESCC, the downstream mRNA binding targets of miR-137 were explored. miR-137 was demonstrated to bind DAAM1 3'-UTR and repressed the expression of DAAM1. The expression of DAAM1 and miR-137 in ESCC was inversely correlated. Additionally, the reintroduction of DAAM1 had the capacity to reverse the negative role of miR- 137 in ESCC cell growth. CONCLUSION: These findings have uncovered the new function of miR-137 in ESCC via negatively regulating DAAM1, suggesting miR-137 as a potent therapeutic candidate for ESCC treatment.

First-Line Chemoradiation With or Without Chidamide (Tucidinostat) in Patients With Intermediate- and High-Risk Early-Stage Extranodal Nasal-Type Natural Killer/T-Cell Lymphoma: A Randomized Phase 2 Study in China.

PURPOSE: We investigated the safety and efficacy profile of intensity-modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, cisplatin (GDP), plus chidamide in the first-line setting for intermediate- and high-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL). METHODS: This was an open-label, randomized phase 2 trial performed at 2 centers in China. Patients were eligible if they were newly-diagnosed with intermediate- and high-risk early-stage ENKTCL with at least one risk factor based on a nomogram-revised risk index: >60 years old, elevated serum lactate dehydrogenase, invasion of the primary tumor, stage II or Eastern Cooperative Oncology Group performance status >1 or stage II disease. Patients were treated with IMRT followed by GDP, with or without chidamide, in the first-line setting. Two-year progression-free survival (PFS) comprised the primary endpoint. Toxicities, the 2-year overall survival (OS), and the response rate comprised the secondary endpoints. RESULTS: Eligible patients (N = 74) were enrolled between May 2015 and December 2019. Among them, 37 patients were treated with IMRT + GDP + chidamide (chidamide group), whereas 37 cases were treated with IMRT + GDP (control group). Follow-up comprised a median of 43.4 months (range, 1.0-74.6 months). The objective response rate was 86.5% in the chidamide group and 78.4% in the control group (P = .359) at the end of treatment completion. The 2 year OS and PFS rates were 89.2% and 75.2% in the chidamide group versus 83.8% (P = .388) and 70.2% (P = .821) in the control group. The main adverse events were hematological toxicities and mucositis, with similar rates in the 2 groups (P > .05). CONCLUSIONS: The addition of chidamide to IMRT + GDP as first-line treatment achieved similar treatment outcomes and tolerable toxicities compared with IMRT + GDP in patients with intermediate- and high-risk early-stage ENKTCL.

Prognostic Nutritional Index, Another Prognostic Factor for Extranodal Natural Killer/T Cell Lymphoma, Nasal Type.

Objective: The prognostic nutritional index (PNI) is a significant prognostic factor in diffuse large B cell lymphoma, follicular lymphoma, and other malignancies. The current study aimed to explore its prognostic role in extranodal natural killer/T cell lymphoma (ENKTL). Methods: Patients diagnosed with ENKTL and treated during 2002 and 2018 (n = 184) were retrospectively recruited. PNI was calculated from albumin concentration (g/L) and total lymphocyte count (*109/L). The association of PNI and overall survival (OS) or progression-free survival (PFS) was assessed in univariate analysis and multivariate Cox regression validated by the 10-fold cross-validation method. Results: Survival analyses showed that both OS and PFS differed significantly between PNI groups stratified by a cutoff value of 49.0. The 3- and 5-year OS were 42.5 and 36.3% in the low-PNI (PNI < 49) subgroup and 70.6% and 63.9% (P < 0.001) in the high-PNI (PNI ≥ 49) subgroup, respectively. The corresponding PFS showed a similar pattern (38.4, 32.4 vs. 64.8, 54.0%, P < 0.001). Multivariate analysis indicated that PNI was significantly independent for both OS (HR = 0.517, 95% CI = 0.322-0.831, P = 0.006) and PFS (HR = 0.579, 95% CI = 0.373-0.899, P = 0.015). Furthermore, integrating PNI into the models of IPI (International Prognostic Index), KPI (Korean Prognostic Index), and PINK (prognostic index of natural killer lymphoma) could improve the area under the curve (AUC) and reduce the integrated Brier score (IBS) and Akaike Information Criterion (AIC) value of each model. Conclusion: PNI was a significant prognostic indicator for ENKTL.

Hemoglobin level, a prognostic factor for nasal extranodal natural killer/T-cell lymphoma patients from stage I to IV: A validated prognostic nomogram.

Although nasal extranodal natural killer/T-cell lymphoma (nasal ENKL) shares some prognostic factors with other lymphomas, seldom studies had explored the prognostic value of hemoglobin. The ENKL cases in stage I-IV during 2000 to 2015 were collected from two medical centers (group A, n = 192), and were randomly divided into the group B (n = 155) and C (n = 37). Although the significant factors identified by the univariate analysis differed between the group A and B, the multivariate Cox regression indicated the same factors. C-index of the model was slightly better than Yang's, but its integrated Brier score (IBS) was obviously lower than Yang's both in the group A and B. Additionally, minimal depth of random survival forest (RSF) classifier confirmed that the prognostic ability of hemoglobin was better than age both in the group A and B. In the calibration of the nomogram, the predicted 3-year or 5-year OS of our nomogram well agreed with the corresponding actual OS. In conclusion, Hemoglobin is a prognostic factor for nasal ENKL patients in stage I - IV, and integrating it into a validated prognostic nomogram, whose generalization error is the smallest among the evaluated models, can be used to predict the patients' outcome.

A comparison of treatment modalities for nasal extranodal natural killer/T-cell lymphoma in early stages: The efficacy of CHOP regimen based concurrent chemoradiotherapy.

This study was designed to evaluate the efficacy of several treatment modalities, including CHOP based concurrent chemoradiotherapy (CCRT), for the patients with stage IE or IIE nasal extranodal NK/T-cell lymphoma (nasal ENKL). The cases were retrieved between 2000 and 2010 (n=94), and were followed to the end of February 2016. The patients were grouped into A (chemotherapy alone; CT alone), B (sequential treatment) and C (CCRT). For those with efficacy evaluation for overall treatment (n=90), CR was attained in 60.0% (18/30), 69.8% (30/43) and 76.5% (13/17) patients in the group A, B and C, respectively. The 5-year OS rate was 35.2%, 41.9% and 70.6% in the group A, B and C, respectively. For patients with early stage diseases (IE and IIE), the ECOG performance status and the Ann Arbor stage were significant prognostic factors for both OS and PFS. Among the stage IE patients, besides the ECOG performance status, three prognostic factors which related to treatments (treatment modalities, efficacy of initial and overall treatment) were significant against OS or PFS. In conclusion, compared to chemotherapy alone and sequential treatment, nasal ENKL patients in early stages, especially stage IE, benefit the most from CHOP based concurrent chemoradiotherapy.