A novel disulfidptosis-related lncRNAs signature for predicting survival and immune response in hepatocellular carcinoma.

The accumulation of intracellular disulfides induces a novel and unique form of metabolic-related cell death known as disulfidptosis. A previous study revealed the prognostic value of a risk model of disulfidptosis-related genes in hepatocellular carcinoma (HCC). However, to date, no studies have investigated the relationship between disulfidptosis-related long non-coding RNAs (DRLs) and HCC. In this study, we collected and analyzed RNA sequencing data from 370 HCC samples to explore the DRLs in the tumorigenesis and development of HCC. By employing Lasso Cox regression and multivariate Cox regression analyses, we identified five prognostic DRLs, which were used to construct a prognostic signature. The signature was subsequently validated using receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, Cox regression analyses, nomograms, and calibration curves. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed, revealing that the DRLs signature was associated with HCC and several cancer-related pathways. Furthermore, the DRLs signature showed correlations with the infiltration of M0 and M1 macrophages, immune-related functions, and multiple immune checkpoints, including PDCD1, LAG3, CTLA4, TIGIT, CD47, and others. Analysis using the tumor immune dysfunction and exclusion (TIDE) approach demonstrated that the DRLs signature could predict the response to immunotherapy. Finally, we screened potential chemotherapy drugs that could sensitize HCC. In conclusion, our novel DRLs signature provides valuable insights into predicting patient survival and immunotherapy responses.

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.

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.

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.

Receptor discordance among primary tumors, brain metastases and extra-brain metastases in patients with breast cancer.

Background: To investigate the expression status of estrogen receptor (ER), progesterone receptor (PR) and HER2 in patients with breast cancer brain metastases (BM). Methods: Patients who underwent craniotomy for BM were included. The status of ER, PR and HER2 (including HER2-low expression) in primary breast tumors (PT), BM and extra-BM (EM) was determined. Results: Between PT and BM, conversion of hormone receptor and HER2 occurred in 28% (30/107) and 12% (10/86) of cases. When considering three-tiered categorization of HER2, the conversion rate reached 31%. In the paired EM and BM (n = 39), the discordance rates were 18%, 3% and 22%, respectively. Conclusion: Receptor discordance was dynamic and relevant, especially using new HER2 categorization.

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.

Comparison of dynamic changes in the peripheral CD8+ T cells function and differentiation in ESCC patients treated with radiotherapy combined with anti-PD-1 antibody or concurrent chemoradiotherapy.

Objective: The systematic immune status of cancer patients undergoing immunotherapy is little known. We prospectively identified the function and differentiation traits of peripheral CD8+ T cells based on our phase 1b clinical trial (NCT03222440) of radiotherapy combined with camrelizumab in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and compared it with concurrent chemoradiotherapy (CCRT). Methods: 19 and 18 patients were included in the cohort of radiotherapy plus camrelizumab and cohort of CCRT treatment. By using flow cytometry, we evaluated the expression levels of PD-1, Eomes, T-bet and IFN-γ (function), CD38 and HLA-DR (activation), and differentiation subsets classified according to the expression levels of CD45RA and CD62L in peripheral CD8+ T cells before and during treatment. Results: Effective binding of anti-PD-1 antibody camrelizumab with PD-1 on CD8+ T cells was detected during treatment. Both two treatments elevated the expression levels of activation molecules CD38 and HLA-DR on CD8+ T cells. PD-1+CD8+ T cells had more activation features than PD-1-CD8+ T cells in two groups and the treatments did not alter these differences. The two treatments activated both PD-1+ and PD-1- CD8+ T cells. PD-1+CD8+ T cells had less Naïve and TEMRA but more Tcm and Tem than PD-1-CD8+ T cells in two groups and both two treatments changed the ratio of memory T cells in PD-1+ and PD-1- cells. RT plus camrelizumab treatment reduced Naïve T cells and TEMRA subsets both in PD-1+ and PD-1- CD8+ T cells while elevated Tcm subset in PD-1+CD8+ T cells and Tem subset in PD-1-CD8+ T cells. CCRT elevated Tcm subset and reduced TEMRA subset in PD-1-CD8+ T cells while did not change any subset in PD-1+CD8+ T cells. Furthermore, patients undergoing radiotherapy plus immunotherapy were found to obtain better prognosis than those receiving CCRT. Conclusions: This study identified the dynamic changes of systematic immune status of patients undergoing treatment. The two treatments had similar activation effects on peripheral CD8+ T cells with different PD-1 properties but had different effects on their differentiation status. These results provided potential clues to the reasons underlying the difference in prognosis of the two treatments.

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 retrospective study comparing definitive chemoradiotherapy vs. chemoradiotherapy followed by surgery in T4 esophageal squamous cell carcinoma patients who were downstaged after neochemoradiotherapy.

BACKGROUND: The outcome of patients with T4 esophageal squamous cell carcinoma (ESCC) is extremely poor. Two distinct therapeutic options are currently available for T4 esophageal cancers: neochemoradiotherapy followed by surgery (CRT-S) and definitive chemoradiotherapy (D-CRT). This study aimed to investigate the clinicopathologic characteristics of T4 ESCC in Chinese patients and compare the survival between the two therapeutic options. METHODS: We retrospectively analyzed 125 patients with clinically unresectable T4 ESCC in Tianjin Medical University Cancer Institute and Hospital from January 2010 to December 2020. Overall survival (OS), progression-free survival (PFS) and associated factors were analyzed. RESULTS: A total of 106 of 125 T4 ESCC patients were downstaged of the tumor by neoadjuvant CRT. Among 106 patients, 32 patients underwent CRT-S, and 74 patients underwent D-CRT. Patients in the CRT-S group had a higher OS (20.4 months vs. un-reached median OS, p = 0.037) and PFS (8.6 months vs. 21.0 months, p = 0.008) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor of PFS. After propensity score matching (PSM), 50 patients (CRT-S = 25; D-CRT = 25) were matched. Among these 50 patients, patients in the CRT-S group had a higher OS (15.6 months vs. un-reached median OS, p = 0.025) and PFS (7.2 months vs. 18.8 months, p = 0.026) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor for PFS. CONCLUSION: We demonstrated that CRT-S was superior to D-CRT for T4 ESCC patients who were downstaged by neo-CRT with respect to longer OS and PFS. Randomized controlled trials involving large population samples are needed to define the standard treatment for T4 ESCC.

Time-spatial analysis of T cell receptor repertoire in esophageal squamous cell carcinoma patients treated with combined radiotherapy and PD-1 blockade.

T cell receptor (TCR) repertoire as a biomarker for predicting immunotherapy efficiency has been widely studied. However, its dynamics during radiotherapy combined with PD-1 blockade is little known. Using paired tumor and blood samples from the phase Ib clinical study (NCT03222440), we investigate the time-spatial TCR repertoire in esophageal squamous cell carcinoma (ESCC) patients treated with first-line definitive radiotherapy concurrently with anti-PD-1 antibody camrelizumab, and also evaluate the association between TCR repertoire and clinical outcomes. TCR sequencing was performed on tumor biopsies (n = 34, 15 pairs) and peripheral CD8+ T cells (n = 36, 18 pairs) collected at baseline and during treatment (after 40 Gy radiation and 2 rounds of camrelizumab). Whole exome sequencing was applied to estimate genomic mutations and tumor mutation burden. We show that the intratumoral TCR repertoire at baseline was correlated with tumor microenvironment and presented heterogeneity inter-individually. T-cell clones inflowed mutually between tumors and peripheral blood under combination treatment, resulting in an elevation of intratumoral TCR diversity. The peripheral CD8+ TCR diversity at baseline, increased tumor-peripheral Morisita-Horn overlap during treatment, and expansion of persistent intratumoral T-cell clones during treatment predicted improved survival. While it is unclear whether radiation contributed to the TCR changes versus PD-1 therapy alone, our results firstly reveal radiotherapy combined with PD-1 blockade greatly promoted time-spatial alteration of TCR repertoire between tumor and peripheral blood, which demonstrate the peripheral CD8+ TCR diversity at baseline and dynamic alteration of intratumoral TCRs acted as potential effective biomarkers of radiotherapy combined with immunotherapy in ESCC.

IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma.

Metastasis contributes to treatment failure in nasopharyngeal carcinoma (NPC) patients. Our study aimed at elucidating the role of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in NPC metastasis and the underlying mechanism involved. IGF2BP3 expression in NPC was determined by bioinformatics, quantitative polymerase chain reaction and immunohistochemistry analyses. The biological function of IGF2BP3 was investigated by using in vitro and in vivo studies. In this study, IGF2BP3 mRNA and protein levels were elevated in NPC tissues. In addition, IGF2BP3 exerted an oncogenic role by promoting epithelial-mesenchymal transition (EMT), thereby inducing NPC cell migration and invasion. Further studies revealed that IGF2BP3 regulated the expression of key regulators of EMT by activating AKT/mTOR signalling, thus stimulating NPC cell migration and invasion. Remarkably, targeting IGF2BP3 delayed NPC metastasis through attenuating p-AKT and vimentin expression and inducing E-cadherin expression in vivo. Moreover, IGF2BP3 protein levels positively correlated with distant metastasis after initial treatment. Importantly, IGF2BP3 expression served as an independent prognostic factor in predicting the overall survival and distant metastasis-free survival of NPC patients. This work identifies IGF2BP3 as a novel prognostic marker and a new target for NPC treatment.

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.

Spatial Distribution and Predictive Significance of Dendritic Cells and Macrophages in Esophageal Cancer Treated With Combined Chemoradiotherapy and PD-1 Blockade.

Background: The first clinical study (NCT03671265) of first-line chemoradiotherapy combined with PD-1 blockade showed promising treatment outcomes in locally advanced esophageal squamous cell carcinoma (ESCC). However, partial patients did not respond to the combination treatment. The roles of dendritic cells (DCs) and macrophages in this combination treatment remain poorly understood. Methods: We performed multiplexed immunofluorescence method to identify CD11c+ DCs, CD68+ macrophages, and their PD-L1- or PD-L1+ subpopulations in paired tumor biopsies (n = 36) collected at baseline and during the combination treatment (after radiation, 40 Gy) from the phase Ib trial (NCT03671265). We applied whole exome sequencing in the baseline tumor biopsies (n = 14) to estimate tumor mutation burden (TMB). We dynamically investigated the spatial distribution of DCs and macrophages under chemoradiotherapy combined with PD-1 blockade, and evaluated the association between their spatial distribution and combination outcome, and TMB. Results: The results showed that high percentages of PD-L1- DCs and macrophages in the baseline tumor compartment, but not in the stromal compartment, predicted improved OS and PFS. Chemoradiotherapy combined with PD-1 blockade promoted DCs and macrophages to migrate closer to tumor cells. During combination treatment, PD-L1- tumor cells were nearest to PD-L1- DCs and macrophages, while PD-L1+ tumor cells were next to PD-L1+ DCs and macrophages. High TMB was closely associated with a shorter distance from tumor cells to DCs and macrophages. Shorter distance between PD-L1+ tumor cells and PD-L1+ DCs or PD-L1- macrophages during the combination was correlated with better OS. Shorter distance between PD-L1- tumor cells and PD-L1- macrophages during combination was associated with both longer OS and PFS. Conclusions: PD-L1- or PD-L1+ DCs and macrophages exhibit distinct spatial distribution in ESCC. The close distance between tumor cells and these antigen-presenting cells (APCs) is critical to the clinical outcome in chemoradiotherapy combined with PD-1 blockade in ESCC patients. Our results highlight the predictive potential of spatial patterns of APCs in chemoradiotherapy combined with immunotherapy and reveal the underlying mechanism of APCs participating in chemoradiotherapy-induced antitumor immune response in ESCC.

Role of clip markers placed by endoscopic ultrasonography in contouring gross tumor volume for thoracic esophageal squamous cell carcinoma: one prospective study.

BACKGROUND: We aimed to analyze the value of metal clip markers guided and placed by endoscopic ultrasonography (EUS) in the delineation of gross tumor volume (GTV) for thoracic esophageal squamous cell carcinoma. METHODS: From September 2016 to September 2018, patients with thoracic esophageal squamous cell carcinoma in Tianjin Medical University Cancer Institute and Hospital were recruited in the prospective trial, NCT02959385. They underwent titanium clips placement on tumor superior and inferior boundaries under EUS by a single expert endosonographer before radiotherapy computed tomography (CT) simulation. According to the clip markers, the reference GTVs were contoured by one experienced radiation oncologist. With the help of the Eclipse treatment planning system, clip markers on CT were concealed. Afterward, two other radiation oncologists with expertise in esophageal cancer delineated GTVs, defined as conventional GTVs, based on endoscopy and barium radiography findings. The two GTVs were compared and analyzed. Subgroup analysis was conducted in different T stage [early (T1 + T2) vs. advanced (T3 + T4)], focus location (upper vs. middle vs. lower segment), and tumor length (<5 vs. >5 cm) groups. RESULTS: The trial recruited 55 patients with 60 thoracic esophageal cancer foci. A total of 111 titanium clips were guided and implanted by EUS. Before CT simulation, two titanium clips at two foci fell off. After the procedure, no case of intolerable esophageal pain, hemorrhage, or perforation occurred. Compared to reference GTVs', discrepancies of conventional GTVs' superior borders were 0.91±0.82 cm (P<0.001), while differences of inferior borders were 0.74±0.63 cm (P<0.001). On the contrary, conventional GTVs' lengths were not significantly different from reference GTVs' with discrepancies 0.08±1.30 cm (P=0.64). Regardless of T stage, tumor location, and tumor length, conventional GTVs' superior and inferior borders were significantly different from reference GTVs', while GTVs' lengths differed insignificantly. CONCLUSIONS: This study confirmed that EUS-placed titanium clips could correct contouring of GTVs in thoracic esophageal cancer in different T stages, tumor locations, and lengths.

Annual report of the esophageal cancer radiation group of the Department of Radiotherapy, Tianjin Medical University Cancer Institute & Hospital.

BACKGROUND: This report describes the clinical work in esophageal cancer radiation group at the Department of Radiotherapy, Tianjin Medical University Cancer Institute & Hospital (TJMUCH). METHODS: We retrospectively analyzed the clinical data of patients with esophageal cancer who received radiotherapy (RT) at TJMUCH during the 5-year period between 2015 and 2019, including RT procedures, RT methods, treatment types, treatment outcomes and complications, and clinical trials. RESULTS: In 2015-2019, 1,464 patients with esophageal cancer received RT at the Department of Radiotherapy, TJMUCH. Of these, 1,176 patients received definitive chemoradiotherapy (CRT), 100 received preoperative neoadjuvant CRT, 120 received postoperative adjuvant RT, 49 received post-relapse RT, and 19 received palliative RT for advanced esophageal cancer. Among the patients who received definitive CRT, the incidences of grade 2 and higher radiation esophagitis, radiation pneumonitis, and leukopenia were 19.4%, 3.6%, and 19.7%, respectively; the incidences of grade 3-4 radiation esophagitis, radiation pneumonitis, and leukopenia were 9.4%, 1.2%, and 5.4%, respectively; no grade 5 acute adverse events were observed. Esophageal fistula was the major side effect during the advanced stage of RT. In 2015-2018, 44 patients (5%, 44/846) developed esophageal fistula; of these, 34 cases occurred after RT, and 10 cases occurred during RT. The overall survival was based on the data of 544 patients with esophageal cancer who underwent definitive RT at TJMUCH between March 2010 and September 2016. The median follow-up time was 21.6 months. The median survival was 19.6 months; and the 1-, 3-, and 5-year overall survival rates were 69.4%, 37.2%, and 32.3%, respectively. In 2015-2019, approximately 201 patients participated in different prospective clinical trials. CONCLUSIONS: RT is a crucial and effective treatment for esophageal cancer. Standardized treatment procedures, multidisciplinary cooperation, are the foundations for good treatment effects. Many promising ongoing clinical trials will be helpful to improve the prognosis and survival of esophageal cancer patients in the future.

The efficacy and safety of simultaneous integrated dose reduction in clinical target volume with intensity-modulated radiotherapy for patients with locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Compelling research to explore the effectiveness of simultaneous integrated dose reduction in clinical target volume (CTV) with intensity-modulated radiotherapy (SIR-IMRT) for locally advanced esophageal squamous cell carcinoma (ESCC) are limited. This study aimed to compare the clinical efficacy and treatment-related toxicity between SIR-IMRT and conventional IMRT (C-IMRT) in the treatment of ESCC. METHODS: From March 2010 to September 2016, the clinical data of 257 patients with ESCC who received definitive IMRT in the Tianjin Medical University Cancer Institute and Hospital were collected and retrospectively analyzed. Among these patients, 137 patients received C-IMRT with a prescribed dose of 60 Gy in 30 fractions for planning target volume (PTV), while 120 patients received SIR-IMRT with a prescribed dose of 60 Gy in 30 fractions for the planning gross tumor volume (PGTV) and a prescribed dose of 54 Gy in 30 fractions for PTV. All of the patients received definitive IMRT with elective nodal irradiation. Locoregional control, survival, treatment toxicity and dose to organs at risk (OAR) were compared between the groups. RESULTS: Patients who received SIR-IMRT showed a similar locoregional failure rate compared to the C-IMRT group (27.5% versus 29.9%, P=0.668). The 1-, 2- and 3-year overall survival (OS) rates were 71.5%, 44.3%, 44.3% vs. 77.9%, 52.1%, 32.9% in the C-IMRT and SIR-IMRT groups, respectively (P=0.825). No significant differences were observed in PFS and LRRFS between the two groups (P=0.880 and P=0.216, respectively). The dose of lung V30 and the maximum dose of spinal cord in the C-IMRT group were significantly higher than those in the SIR-IMRT group (P=0.013, P=0.047). The incidence of acute radiation esophagitis was significantly lower in the SIR-IMRT group (P=0.046), although no statistical difference was observed in the incidence of acute severe adverse events between the two groups. CONCLUSIONS: SIR-IMRT offers an effective and safe option for patients with unresectable ESCC who receive definitive RT. Further prospective and larger sample size studies are warranted to confirm our results.