Adding simultaneous integrated boost to whole brain radiation therapy improved intracranial tumour control and minimize radiation-induced brain injury risk for the treatment of brain metastases.

BACKGROUND: Brain metastases (BMs) are the most frequent intracranial tumours associated with poor clinical outcomes. Radiotherapy is essential in the treatment of these tumours, although the optimal radiation strategy remains controversial. The present study aimed to assess whether whole brain radiation therapy with a simultaneous integrated boost (WBRT + SIB) provides any therapeutic benefit over WBRT alone. METHODS: We included and retrospectively analysed 82 patients who received WBRT + SIB and 83 who received WBRT alone between January 2012 and June 2021. Intracranial progression-free survival (PFS), local tumour control (LTC), overall survival (OS), and toxicity were compared between the groups. RESULTS: Compared to WBRT alone, WBRT + SIB improved intracranial LTC and PFS, especially in the lung cancer subgroup. Patients with high graded prognostic assessment score or well-controlled extracranial disease receiving WBRT + SIB had improved intracranial PFS and LTC. Moreover, WBRT + SIB also improved the long-term intracranial tumour control of small cell lung cancer patients. When evaluating toxicity, we found that WBRT + SIB might slightly increase the risk of radiation-induced brain injury, and that the risk increased with increasing dosage. However, low-dose WBRT + SIB had a tolerable radiation-induced brain injury risk, which was lower than that in the high-dose group, while it was comparable to that in the WBRT group. CONCLUSIONS: WBRT + SIB can be an efficient therapeutic option for patients with BMs, and is associated with improved intracranial LTC and PFS. Furthermore, low-dose WBRT + SIB (biologically effective dose [BED] ≤ 56 Gy) was recommended, based on the acceptable risk of radiation-induced brain injury and satisfactory tumour control. TRIAL REGISTRATION: Retrospectively registered.

Low radiotherapy dose is suitable for brain metastases in SCLC compared with high dose.

Objective: This study was designed to evaluate the suitable radiotherapy dose in SCLC patients with BM. Methods: A retrospective analysis was performed among 121 patients on the prognosis of BM of SCLC who were admitted to our hospital from 2013 to 2023. They all received first line chemotherapy. 80 patients of them received TRT after chemotherapy. The Chi square method was used to compare the categorical data. Univariate survival analysis was estimated by Kaplan Meier method and the logrank was used to compare survival curves between groups. A multivariate prognostic analysis was made by the Cox proportional hazard model. The iOS and iLC of two groups of low dose and high dose were analyzed after propensity score matching (PSM). Results: In all the patients, the median follow-up time was 18.6 months (range 6.30~85.7), the 2-year iOS and iLC rates were 15.4% and 70.3%, respectively, and cerebral necrosis occurred in 2 patients. In univariate analysis related to iOS, extracranial disease control (p=0.023), higher DS-GPA (≥2) (p=0.016), immunotherapy (p=0.049), low-dose(p=0.030), and WBRT+SIB (p=0.009) were significantly associated with an increase in survival rate. After PSM, the 2-year iOS of low dose (n=49) was significantly higher than that of high dose (n=49) (P=0.025), while the 2-year iLC was not significantly improved (P=0.267). In DS-GPA < 2 subgroup, the iOS of low dose group was significantly higher than that of high dose group (p=0.019). In the DS-GPA ≥ 2 subgroup, the 2-year iLC of the low dose group was significantly inferior than that of the high dose group (p=0.044). Conclusions: The iLC was improved along with increasing radiotherapy dose, but high dose had inferior iOS compared to low dose, while there were not significantly improving iLC when radiotherapy BED >56Gy. But in patients with DS-GPA≥2 subgroup, high dose brought better iLC benefits.

Predictive and prognostic markers from endoscopic ultrasound with biopsies during definitive chemoradiation therapy in esophageal squamous cell carcinoma.

INTRODUCTION: Endoscopic ultrasound (EUS) may play a role in evaluating treatment response after definitive chemoradiation therapy (dCRT) for esophageal squamous cell carcinoma (ESCC). This study explored the prognostic markers of EUS with biopsies and developed two nomograms for survival prediction. METHODS: A total of 821 patients newly diagnosed with ESCC between January 2015 and December 2019 were reviewed. We investigated the prognostic value of the changes in tumor imaging characteristics and histopathological markers by an interim response evaluation, including presence of stenosis, ulceration, tumor length, tumor thickness, lumen involvement, and tumor remission. Independent prognostic factors of progression-free survival (PFS) and overall survival (OS) were determined using Cox regression analysis and further selected to build two nomogram models for survival prediction. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to respectively assess its discriminatory capacity, predictive accuracy, and clinical usefulness. RESULTS: A total of 155 patients were enrolled in this study and divided into the training (109 cases) and testing (46 cases) cohorts. Tumor length, residual tumor thickness, reduction in tumor thickness, lumen involvement, and excellent remission (ER) of spatial luminal involvement in ESCC (ER/SLI) differed significantly between responders and non-responders. For patients undergoing dCRT, tumor stage (P = 0.001, 0.002), tumor length (P = 0.013, 0.008), > 0.36 reduction in tumor thickness (P = 0.004, 0.004) and ER/SLI (P = 0.041, 0.031) were independent prognostic markers for both PFS and OS. Time-dependent ROC curves, calibration curves, and DCA indicated that the predicted survival rates of our two established nomogram models were highly accurate. CONCLUSION: Our nomogram showed high accuracy in predicting PFS and OS for ESCC after dCRT. External validation and complementation of other biomarkers are needed in further studies.

Effects of PEG in patients with esophageal squamous cell carcinoma during concurrent chemoradiotherapy: a prospective study.

BACKGROUND AND AIMS: This prospective study aimed to compare the changes in nutritional status and adverse events among patients with esophageal squamous cell carcinoma who received enteral nutrition through oral intake, PEG, and an enteral nasogastric tube (NGT) during concurrent chemoradiotherapy (CCRT). METHODS: Of 141 included patients, 38, 74, and 29 patients were fed through oral intake, PEG, and NGTs, respectively. The clinical characteristics and baseline nutritional status of the 3 groups were recorded and analyzed. The Patient-Generated Subjective Global Assessment score, skeletal muscle index, and quality of life were evaluated before and after CCRT; the incidence of adverse events during feeding using PEG and NGTs was also recorded. The correlations among the different nutritional pathways and the CCRT-related adverse events (eg, radiation esophagitis and myelosuppression) were assessed. RESULTS: At baseline, the oral intake group had a significantly better nutritional status and lower disease stage than those in the PEG and NGT groups. However, during CCRT, the oral intake group exhibited the most significant decreases in weight and skeletal muscle index. The synchronous chemotherapy completion rate was the highest in the PEG group. Multivariate analysis showed that the planning tumor volume and oral intake and NGT feeding pathways were associated with radiation esophagitis of at least grade 2. CONCLUSIONS: We found that PEG effectively maintained the body weight and skeletal muscle index of patients with esophageal cancer during CCRT. PEG also improved the synchronous chemotherapy completion rate and reduced the occurrence of at least grade 2 radiation esophagitis. (Clinical trial registration number: NCT04199832.).

Cutaneous Lymphadenoma: A Case Report and Literature Review.

Cutaneous lymphadenoma (CL) is an uncommon epithelioid tumor that is usually present on the head and face. It was first described by Santa Cruz and Barr in 1987, as a lymphoepithelial tumor, and was renamed as CL in 1991. Although CL is considered as a benign tumor, there are cases of recurrence after shave excision and metastasis to regional lymph nodes. Correct diagnosis and complete resection are of great importance. Here, we report a typical case of CL and make a comprehensive review of this rare skin tumor.

Radiotherapy plus camrelizumab affects peripheral CD8 T-cell differentiation subsets expressing PD-1, TIGIT, and CTLA-4 in esophageal squamous cell carcinoma.

Our previous phase Ib trial (NCT03222440) showed that radiotherapy plus the anti-PD-1 antibody camrelizumab is a safe and feasible first-line therapy for locally advanced esophageal squamous cell carcinoma. In this study, we divided peripheral CD8 T-cell differentiation subsets into 4 subpopulations (naive T cells, central memory T cells, effector memory T cells, and CD45RA+ effector memory T cells). We then investigated the influence of radiotherapy plus camrelizumab therapy on the proportions of the 4 subsets and their PD-1, TIGIT, and CTLA-4 expression as well as their proliferative activity and compared the effects with those of concurrent chemoradiotherapy. Nineteen and 15 patients with esophageal squamous cell carcinoma who received radiotherapy plus camrelizumab therapy and concurrent chemoradiotherapy, respectively, were enrolled in this study. We isolated peripheral blood mononuclear cells from these patients before treatment and longitudinally after the delivery of 40 Gy radiotherapy. Flow cytometry was conducted to detect peripheral CD8 T-cell subsets and PD-1, TIGIT, CTLA-4, and Ki67 expression levels in patients with esophageal squamous cell carcinoma. We found that radiotherapy plus camrelizumab therapy did not change the proportions of the 4 subsets or the expression of CTLA-4, but this therapy decreased PD-1 expression by the 4 subsets and TIGIT expression by effector memory T cells, as well as significantly enhanced the proliferative activity of CD8 T cells, whereas concurrent chemoradiotherapy produced different effects. In addition, we further identified peripheral biomarkers that potentially predict the outcome of radiotherapy plus camrelizumab therapy.

Immunotherapy with or without radiotherapy for metastatic or recurrent esophageal squamous cell carcinoma: A real-world study.

Background and purpose: To evaluate the efficiency and safety of immunotherapy combined with or without radiotherapy (RT) for metastatic or recurrent esophageal squamous cell carcinoma (ESCC). Methods: We retrospectively reviewed data of 127 patients with metastatic or recurrent ESCC, who received immunotherapy with or without RT at Tianjin Medical University Cancer Institute between 2017 and 2021. Results: The median follow-up time was 15.7 months (95 % confidence interval (CI): 12.42-18.99). The median PFS of the RT and NRT groups was 5.45 months (95 % CI: 2.89-8.28) and 4.60 months (95 % CI: 3.75-7.06), respectively (P = 0.660). The median OS was 11.9 (95 % CI: 8.61-19.2) and 10.3 (95 % CI: 7.56-15.8) months, respectively (P = 0.890). The median PFS of locoregional recurrence patients in the RT and NRT groups was 11.27 months (95 % CI: 2.45-20.09) and 4.17 months (95 % CI: 2.64-5.71), respectively (P = 0.081). The median OS of locoregional recurrent patients in the RT and NRT groups was 19.48 months (95 % CI: 8.37-30.60) and 7.69 months (95 % CI: 3.45-11.93), respectively (P = 0.026). 64 % of patients in the RT group and 30 % of patients in the NRT group experienced an improvement in dysphagia (P = 0.033). No significant increase in treatment-related toxicity was observed in the RT group compared with the NRT group, except for some hematological complications. Conclusions: Locoregional recurrent patients gained survival benefits from immunotherapy combined with RT. The combination of immunotherapy and RT was safe in metastatic/recurrent ESCC patients. RT for the esophagus leads to the improvement of dysphagia compared to immunotherapy alone.

Prognostic values of the gross volume of metastatic lymph nodes in patients with esophageal squamous cell carcinoma treated with definitive concurrent chemoradiotherapy.

Purpose: We aim to explore whether the gross volume of metastatic lymph nodes (GTVnd) and the gross volume of primary tumor (GTVp) could be prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT). Methods: We retrospectively analyzed 252 ESCC patients treated with dCCRT in the era of intensity-modulated radiation therapy (IMRT) at our institution. The cut-off value for the GTVnd derived from the restricted cubic splines (RCS) was determined. Univariate and multivariate Cox proportional hazard models were performed to determine the association between GTVnd and prognosis. we performed recursive partitioning analysis (RPA) method using GTVnd to develop a new risk stratification (TGTVndM). Moreover, the linear trend χ2, likelihood ratio χ2, and akaike information criterion (AIC) were used to determine the prognostic value between the TNM and TGTVndM staging systems. Results: The five-year overall survival (OS) rate was 30.6%, with a median follow-up of 38 months. The cut-off value of GTVnd determined by the RCS was 4.35 cm3. GTVnd≥4.35 cm3 was an independent and significant negative prognostic factor for OS (HR=1.949, P<0.001), progression free survival (PFS) (HR=1.425, P=0.048), and distance metastasis free survival (DMFS) (HR=2.548, P=0.001). In multivariable analysis, gender, clinical T stage, and GTVnd were independently associated with OS. RPA segregated patients into 3 prognostic groups: high risk (T1-4 GTVnd≥4.35, n=126, III stage), intermediate risk (T4 GTVnd<4.35,n=38,II stage), and low risk(T1-3GTVnd<4.35, n=88, I stage). The 5-year OS(P<0.001), PFS (P=0.002), and DMFS (P=0.001) were significantly worse in high-risk group in comparison with the intermediate and low risk groups. Compared with the TNM staging system, the clinical T stage combined with GTVnd (TGTVndM) had a higher linear trend χ2 (26.38 versus 25.77), higher likelihood ratio χ2 (24.39 versus 20.69), and lower AIC (1255.07 versus 1260.06). Conclusions: GTVnd may serve as a good prognostic factor in predicting distant metastasis and death for ESCC patients treated with dCCRT. The TGTVndM staging system demonstrated superior accuracy for predicting OS and could serve as a more effective prognostic guidance for unresectable ESCC patients.

A Clinical Scoring Model to Predict the Effect of Induction Chemotherapy With Definitive Concurrent Chemoradiotherapy on Esophageal Squamous Cell Carcinoma Prognosis.

PURPOSE: The aim of the study was to compare the clinical outcomes of induction chemotherapy (IC) followed by definitive concurrent chemoradiotherapy (dCCRT) versus chemoradiotherapy alone in patients with esophageal squamous cell carcinoma (ESCC) on the basis of a clinical scoring model. METHODS: A retrospective review of 599 patients with ESCC treated with dCCRT at our institution from 2010 to 2019 was conducted. The patients were divided into two groups based on whether they received IC. A clinical scoring model was performed using the significant variables obtained from the multivariate analysis. The PFS and OS rates were estimated using the Kaplan-Meier method. RESULTS: During the study period, 182 patients receiving IC followed by dCCRT and 417 dCCRT alone were identified. No significant differences in the PFS and OS rates were observed between the IC group (P=0.532) and the non-IC group (P=0.078). A clinical scoring model was constructed based on independent prognostic factors with scores ranging from 0 to 10.4. The patients were divided into high- and low-risk groups by using the median score as the cutoff value. The PFS rate of patients receiving IC was higher than that of patients treated without IC (P=0.034), while there was no improvement in the OS rate (P=0.794) in the high-risk group. No significant differences in the PFS (P=0.207) or OS (P=0.997) rate were found between the two treatment groups in the low-risk group. CONCLUSIONS: The addition of IC followed by dCCRT for patients with ESCC might be associated with better PFS rates based on a clinical scoring model but has no impact on OS rates. Further prospective studies are warranted for the validation of this model.

DNA methylation mediated down-regulation of ANGPTL4 promotes colorectal cancer metastasis by activating the ERK pathway.

Background: Colorectal cancer (CRC) imposes significant health burden and is increasing in incidence. NGPTL4 has been implicated in the development of CRC. The present study aimed to investigate the molecular mechanisms by which ANGPTL4 expression might regulate epithelial-mesenchymal transition (EMT) and the tumor microenvironment in CRC. Methods: CRC and para-carcinoma tissues were collected from 67 CRC patients. ANGPTL4 expression levels and DNA methylation of ANGPTL4 promoter region were determined. Next, the migration and invasion capacities of CRC cells were assessed. Immunofluorescence and Western blot were used to identify the signaling pathways by which ANGPTL4 mediated tumor metastasis. A tumorigenesis mice model with transplanted fibroblast cells and ANGPTL4 overexpressed CRC cells was established to investigate the effects of ANGPTL4 on the metastasis of cancer cells in vivo. Results: ANGPTL4 was significantly decreased in CRC tissues and DNA hypermethylation was involved in the regulation of ANGPTL4. Mechanistically, ANGPTL4 induced activation of cancer-associated fibroblasts in the tumor microenvironment and promoted EMT in CRC cells through the ERK signaling pathway. In vivo, the overexpression of ANGPTL4 was found to inhibit the metastasis of tumor cells in lung tissues. Conclusion: DNA hypermethylation induced ANGPTL4 downregulation promoted the activation of cancer-associated fibroblasts and epithelial mesenchymal transformation of CRC cells via the ERK signaling pathway, thereby promoting invasion and metastasis in CRC.

Peripheral blood CD45RO+T cells is a predictor of the effectiveness of neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

ABSTRACT: To investigate the relationship between the changes in circulating CD45RO+T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally advanced rectal cancer.The clinicopathological data of 185 patients with rectal cancer who received neoadjuvant therapy in the General Surgery Department of Beijing Chaoyang Hospital affiliated to Capital Medical University from June 2015 to June 2017 were analyzed. Venous blood samples were collected 1 week before neoadjuvant therapy and 1 week before surgery, and the expression of CD45RO+T was detected by flow cytometry. The receiver operating characteristic curve analysis was used to determine the optimal cut-off point of CD45RO+ratio. Log-rank test and multivariate Cox regression were used to analyze the overall survival rate (OS) and disease-free survival rate (DFS) associated with CD45RO+ratio.Circulating CD45RO+ratio of 1.07 was determined as the optimal cut-off point and CD45RO+ratio-high was associated with lower tumor regression grade grading (P = .031), T stage (P = .001), and tumor node metastasis (TNM) stage (P = .012). The 3-year DFS and OS rate in the CD45RO+ratio-high group was significantly higher than that in the CD45RO+ratio-low group (89.2% vs 60.1%, P<.001; 94.4% vs 73.2%, P<.001). The multivariate Cox analysis revealed that elevated CD45RO+ratio was an independent factor for better DFS (OR, 0.339; 95% CI, 0.153-0.752; P = .008) and OS (OR, 0.244; 95% CI,0.082-0.726; P = .011).Circulating CD45RO+ratio could predict the tumor regression grade of neoadjuvant therapy for rectal cancer, as well as long-term prognosis. These findings could be used to stratify patients and develop alternative strategies for adjuvant therapy.

Long term follow-up of inguinal endometriosis.

BACKGROUND: Inguinal endometriosis (IEM) is a rare extra pelvic endometriosis. Here, we study the clinical characteristics, management strategies, and long-term gynecological outcomes of IEM patients at Beijing Chaoyang Hospital. CASE PRESENTATION: Three patients presented with a total of four lesions (one on the left side, one on the right side, and one bilaterally). The diameters of the four lesions were 2 cm, 2 cm, 3.5 cm and 1.5 cm, respectively. Two patients were admitted with inguinal hernias. Two patients were admitted with endometrioses-one with ovarian endometriosis and one with pelvic endometriosis. The hernia sac was repaired concomitantly via excision of the round ligament in two patients. One patient underwent a concomitant laparoscopy for gynecologic evaluations, including an ablation to the peritoneal endometriosis, and resection of the left uterosacral ligament endometriosis and pelvic adhesiolysis. All lesions were located on the extraperitoneal portion of the round ligament and were diagnosed histologically. No recurrence was observed in the inguinal region. All patients diagnosed with adenomyosis were treated with medication alone without any complaints. CONCLUSIONS: Inguinal endometriosis can occur simultaneously with pelvic endometriosis. In most cases, a concomitant hernia sac appears together with groin endometriosis. Clinical management should be individualized and performed in tandem with general practitioners and obstetrics & gynecology experts. Pelvic disease, in particular, should be followed-up by a gynecologist.

Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer.

BACKGROUND AND OBJECTIVES: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. METHODS: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. RESULTS: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. CONCLUSIONS: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.

Epidermis Microstructure Inspired Graphene Pressure Sensor with Random Distributed Spinosum for High Sensitivity and Large Linearity.

Recently, wearable pressure sensors have attracted tremendous attention because of their potential applications in monitoring physiological signals for human healthcare. Sensitivity and linearity are the two most essential parameters for pressure sensors. Although various designed micro/nanostructure morphologies have been introduced, the trade-off between sensitivity and linearity has not been well balanced. Human skin, which contains force receptors in a reticular layer, has a high sensitivity even for large external stimuli. Herein, inspired by the skin epidermis with high-performance force sensing, we have proposed a special surface morphology with spinosum microstructure of random distribution via the combination of an abrasive paper template and reduced graphene oxide. The sensitivity of the graphene pressure sensor with random distribution spinosum (RDS) microstructure is as high as 25.1 kPa-1 in a wide linearity range of 0-2.6 kPa. Our pressure sensor exhibits superior comprehensive properties compared with previous surface-modified pressure sensors. According to simulation and mechanism analyses, the spinosum microstructure and random distribution contribute to the high sensitivity and large linearity range, respectively. In addition, the pressure sensor shows promising potential in detecting human physiological signals, such as heartbeat, respiration, phonation, and human motions of a pushup, arm bending, and walking. The wearable pressure sensor array was further used to detect gait states of supination, neutral, and pronation. The RDS microstructure provides an alternative strategy to improve the performance of pressure sensors and extend their potential applications in monitoring human activities.

Graphene-Paper Pressure Sensor for Detecting Human Motions.

Pressure sensors should have an excellent sensitivity in the range of 0-20 kPa when applied in wearable applications. Traditional pressure sensors cannot achieve both a high sensitivity and a large working range simultaneously, which results in their limited applications in wearable fields. There is an urgent need to develop a pressure sensor to make a breakthrough in both sensitivity and working range. In this paper, a graphene-paper pressure sensor that shows excellent performance in the range of 0-20 kPa is proposed. Compared to most reported graphene pressure sensors, this work realizes the optimization of sensitivity and working range, which is especially suitable for wearable applications. We also demonstrate that the pressure sensor can be applied in pulse detection, respiratory detection, voice recognition, as well as various intense motion detections. This graphene-paper pressure sensor will have great potentials for smart wearable devices to achieve health monitoring and motion detection.

Synchronous double cancers of colonic large cell neuroendocrine carcinoma and gastric squamous-cell carcinoma: a case report and review of literature.

Either colonic large cell neuroendocrine carcinoma (LCNEC) or gastric squamous-cell carcinoma (SCC) is extremely rare, with a very poor prognosis due to the high rate of distant metastases. Here, we report the first case of synchronous double malignancies in form of colonic LCNEC and gastric SCC. A 66-year male underwent a right hemicolectomy for a mass obstructing the ascending colon and an emergent gastroscopic hemostasis for another hemorrhagic stomach mass. Histopathological examination confirmed colonic LCNEC displaying the characteristic of large, vesicular nuclei with variable amounts of cytoplasm and gastroscopic biopsy revealed poorly-differentiated gastric SCC. Immunohistochemical staining of LCNEC demonstrated positive activities for chromogranin A, synaptophysin, CD56, NSE, ki-67 (>95%), but negative for CD99, CK20 and TTF-1. The patient had suffered from an accelerated growth of multiple liver metastases after surgery, suggestive of concomitant tumor resistance (CR), and survived 2 months after discharge.