Association of preoperative muscle-adipose index measured by computed tomography with survival in patients with esophageal squamous cell carcinoma.

BACKGROUND: Conventional nutritional metrics are closely associated with the prognosis of patients with radically resected esophageal squamous cell carcinoma (ESCC). Nevertheless, the prognostic implications of muscle and adipose tissue composite indexes in ESCC remain unknown. METHODS: We retrospectively analyzed clinicopathological data of 304 patients who underwent resected ESCC. To obtain measurements of the muscle and adipose indexes, preoperative computed tomography (CT) images were used to quantify skeletal-muscle adipose tissue. The diagnostic threshold for muscle-adipose imbalance was determined using X-tile software and used to analyze the association between the muscle-adipose index (MAI) and survival. Instantaneous risk of recurrence was assessed using a hazard function. We constructed a nomogram based on the MAI and other clinical characteristics and established a novel predictive model with independent prognostic factors. The prognostic capabilities of these nomograms were evaluated using calibration curves, receiver operating characteristic (ROC) curves, and decision-curve analysis (DCA). RESULTS: The overall survival (OS) and disease-free survival (DFS) rates in the muscle-adipose-balanced group were significantly better than those in the muscle-adipose-imbalanced group. Multivariate analyses revealed that the MAI, prognostic nutritional index (PNI), tumor stage, and tumor differentiation were independent prognostic factors for OS and DFS in patients with resected ESCC (P < 0.05). The nuclear density curve indicated a lower risk of recurrence for patients in the muscle-adipose-balanced group than that for their imbalanced counterparts. Conversely, the nuclear density curve for PNI was confounded. Postoperative radiotherapy- (RT) benefit analysis demonstrated that patients with ESCC in the muscle-adipose-balanced group could benefit from adjuvant RT. CONCLUSION: This study confirmed that preoperative MAI could serve as a useful independent prognostic factor in patients with resected ESCC. A nomogram based on the MAI and other clinical characteristics could provide individualized survival prediction for patients receiving radical resection. Timely and appropriate nutritional supplements may improve treatment efficacy.

CT imaging-based radiomics signatures improve prognosis prediction in postoperative colorectal cancer.

OBJECTIVE: To investigate the use of non-contrast-enhanced (NCE) and contrast-enhanced (CE) CT radiomics signatures (Rad-scores) as prognostic factors to help improve the prediction of the overall survival (OS) of postoperative colorectal cancer (CRC) patients. METHODS: A retrospective analysis was performed on 65 CRC patients who underwent surgical resection in our hospital as the training set, and 19 patient images retrieved from The Cancer Imaging Archive (TCIA) as the external validation set. In training, radiomics features were extracted from the preoperative NCE/CE-CT, then selected through 5-fold cross validation LASSO Cox method and used to construct Rad-scores. Models derived from Rad-scores and clinical factors were constructed and compared. Kaplan-Meier analyses were also used to compare the survival probability between the high- and low-risk Rad-score groups. Finally, a nomogram was developed to predict the OS. RESULTS: In training, a clinical model achieved a C-index of 0.796 (95% CI: 0.722-0.870), while clinical and two Rad-scores combined model performed the best, achieving a C-index of 0.821 (95% CI: 0.743-0.899). Furthermore, the models with the CE-CT Rad-score yielded slightly better performance than that of NCE-CT in training. For the combined model with CE-CT Rad-scores, a C-index of 0.818 (95% CI: 0.742-0.894) and 0.774 (95% CI: 0.556-0.992) were achieved in both the training and validation sets. Kaplan-Meier analysis demonstrated a significant difference in survival probability between the high- and low-risk groups. Finally, the areas under the receiver operating characteristics (ROC) curves for the model were 0.904, 0.777, and 0.843 for 1, 3, and 5-year survival, respectively. CONCLUSION: NCE-CT or CE-CT radiomics and clinical combined models can predict the OS for CRC patients, and both Rad-scores are recommended to be included when available.

IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment.

Background: Lung cancer has some of the highest morbidity and mortality worldwide among cancers, with non-small cell lung cancer (NSCLC) accounting for 85% of lung cancer diagnoses. Severe pulmonary hemorrhage (PH) is a serious potential adverse event in the treatment of lung cancer with bevacizumab. Significant clinical differences have been observed between patients with lung adenocarcinoma (LUAD) and those with lung squamous cell carcinoma (LUSC) after bevacizumab treatment; however, the underlying causes is unclear and requires further study. Methods: First, tumor tissues from LUAD and LUSC patients were stained with antibodies targeting CD31 and CD34 to assess the difference in microvessel density (MVD). Tube formation assays were performed using HMEC-1 cells cocultured with lung cancer cells. Single-cell sequencing data obtained from lung cancer tissues were then downloaded and analyzed to identify differentially expressed genes related to angiogenesis in LUAD and LUSC tumors. Real-time polymerase chain reaction, immunofluorescence analysis, small interfering RNA analysis, and enzyme-linked immunosorbent assay were performed to clarify the underlying causes. Results: The MVD of LUAD tissues was higher than that of LUSC tissues. Additionally, endothelial cells cocultured with LUAD cells had a higher MVD than did those cocultured with LUSC cells. Although bevacizumab mainly targets vascular endothelial growth factor (VEGF), the expression of VEGF in LUSC and LUAD cells was not significantly different (P>0.05). Further experiments showed that interferon regulatory factor 7 (IRF7) and interferoninduced protein with tetratricopeptide repeats 2 (IFIT2) were differentially expressed between LUSC and LUAD tumors. Higher IRF7 levels and lower IFIT2 levels in LUAD tumors were associated with higher MVD in LUAD tissues, which may be responsible for the different hemorrhage outcomes after bevacizumab treatment. Conclusions: Our data indicated that IRF7 and IFIT2 may account for the differential hemorrhage outcomes in patients with NSCLC after bevacizumab treatment, revealing a new mechanism underlying bevacizumab-induced pulmonary hemoptysis.

Low-dose radiotherapy promotes the formation of tertiary lymphoid structures in lung adenocarcinoma.

Purpose: A tertiary lymphoid structure (TLS) refers to an organized infiltration of immune cells that is linked to a positive prognosis and improved response to immunotherapy. However, methods that promote TLS formation are limited and challenging to implement in clinical settings. In this study, we aimed to promote the formation and maturation of TLSs in lung adenocarcinoma (LUAD) by combining low-dose radiotherapy (LDRT) with immunotherapy. Methods: Tissue sections from 198 patients who had undergone surgery were examined. Risk factors for patient survival were assessed, and the relationship between TLSs and five-year survival was analyzed. The Kras-LSL-G12D spontaneous lung cancer mouse model was used to screen the optimal irradiation dose (0/1/2 Gy whole lung irradiation) for promoting TLS formation. LDRT combined with anti-PD-1 was used to promote the formation and maturation of TLSs. Results: TLS+, TLSHigh, TLS+GC+ and CD8High within TLS+ were associated with a favorable prognosis. LDRT increased the formation of early TLSs in the Kras-LSL-G12D lung cancer mouse model. In addition, LDRT combined with anti-PD-1 treatment can significantly improve the maturity of TLSs in mouse LUAD, resulting in greater antitumor effects. This antitumor effect was strongly associated with the number of CD8+ T cells within the TLSs. Conclusion: We successfully applied LDRT combined with PD-1 inhibitor therapy for the first time, which increased both the quantity and maturity of TLSs in lung cancer. This approach achieved a promising antitumor effect.

Methylated PTGER4 is better than CA125, CEA, Cyfra211 and NSE as a therapeutic response assessment marker in stage IV lung cancer.

Real-time assessment of therapeutic response in patients with advanced lung cancer presents a major challenge throughout the treatment process. Currently, computed tomography imaging is often used; however, it is radiation-based and hysteretic and is not suitable for repeated use as a real-time assessment. Blood biomarkers represent a novel solution for assessing therapeutic response in patients with advanced lung cancer. In the present study, the efficacy of a methylation marker [methylated prostaglandin E receptor 4 (mPTGER4)] and four protein markers [carcinoma antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin 19-fragments (cyfra21-1) and neuron-specific enolase (NSE)] were simultaneously evaluated to determine their potential in facilitating therapeutic response monitoring as well as their prognostic values in patients with stage IV lung cancer. The results indicated that, following treatment, the blood levels of methylated PTGER4 and NSE had significantly decreased, and mPRGER4, CA125, CEA and NSE exhibited a significant decrease in percentage level. Since mPTGER4 exhibited a higher rate of positive detection prior to therapy, and a greater response of sensitivity to therapy compared to the protein markers, it may represent an improved marker for the monitoring of therapeutic response. The efficacy of the markers in predicting the overall survival (OS) rate of patients with stage IV lung cancer was also assessed. Results from the follow-up of patients (up to 891 days) revealed that the blood levels of mPTGER4, CA125 and NSE before treatment were able to predict overall survival (OS) rate. Additionally, the percentage change in expression levels of CA125, CEA and NSE was also able to predict the OS rate. In conclusion, the present results indicate that mPTGER4 represents an improved biomarker for monitoring therapeutic efficacy compared with CA125, CEA, Cyfra21-1 and NSE. In predicting the long-term survival of patients with stage IV lung cancer; however, the pre-treatment levels of mPTGER4, CA125 and NSE and the percentage changes of CA125, CEA and NSE may be used as the markers.

Intensity-modulated radiotherapy plus nimotuzumab with or without concurrent chemotherapy for patients with locally advanced nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of intensity-modulated radiotherapy (IMRT) plus nimotuzumab with or without concurrent chemotherapy (CCT) for patients with locally advanced nasopharyngeal carcinoma (LA-NPC). PATIENTS AND METHODS: A total of 50 newly diagnosed patients with LA-NPC treated at the Affiliated Hospital of Jiangnan University between November 2011 and January 2017 were retrospectively analyzed. All patients received the combined treatment modality of nimotuzumab plus IMRT. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Neoadjuvant, concurrent or adjuvant chemotherapy with the doublet regimen of taxanes (docetaxel or paclitaxel) plus platinum (cisplatin or nedaplatin) were administered. Among the 50 patients, 43 (86.0%) received ≥6 cycles of nimotuzumab (median 7 cycles, range 2-14 cycles) and 29 (58.0%) received two cycles of CCT with docetaxel plus nedaplatin. RESULTS: With a median follow-up of 28.0 months, the 2-year progression-free survival (PFS) and overall survival were 83.29% (95% confidence interval [CI]: 67.93%-91.72%) and 97.67% (95% CI: 84.62%-99.67%), respectively. Both univariate and multivariate analyses revealed that cycles of nimotuzumab were significantly associated with PFS. Patients who received ≥6 cycles of nimotuzumab showed a better PFS than those receiving <6 cycles (P=0.006), whereas the addition of CCT failed to improve PFS. Oral mucositis was the most common adverse event, which was recorded as grade 3-4 in 18 (36.0%) patients. Besides, two (4.0%) patients experienced nimotuzumab-related anaphylaxis, and no skin rash was found in any patient. Subgroup analysis revealed that the patients who received CCT had more grade 3-4 adverse events as compared to those who did not receive CCT (62.1% vs 33.3%, P=0.045). CONCLUSION: The regime of nimotuzumab plus IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC. Further clinical trials are needed to confirm these findings.