BACKGROUND:Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line standard treatment for advanced lung adenocarcinoma with common EGFR sensitive mutations (exon 19 E746-A750 deletion and exon 21 L858R). However, the optimal management for rare or compound EGFR mutations remains undefined. CASE PRESENTATION:We report a case of advanced lung adenocarcinoma with a rare compound EGFR L747S/L858R mutation. The patient underwent four lines of therapy, showing significant responses to alternating cycles of Osimertinib and Pembrolizumab-chemotherapy, despite intervening disease progression. The clinical course culminated in fatal treatment-induced myelosuppression, with an overall survival exceeding 43 months. CONCLUSION:This case underscores dynamic clonal evolution in advanced NSCLC: the initial L747S/L858R clone showed Osimertinib sensitivity, while subsequent resistance revealed a distinct profile (distinct TP53 mutation, MET amplification, high PD-L1/TMB) that explained the durable response to Pembrolizumab. These findings provide crucial evidence for sequential therapy strategies in compound EGFR mutations. Our findings also highlight the utility of Next Generation Sequencing (NGS) in identifying targetable resistance mechanisms, enabling prolonged survival in patients with compound EGFR mutations and offering valuable insights for clinical decision-making.

Background: Primary small cell carcinoma of the oesophagus (PSCCE) is a gastrointestinal tumour of rare onset. The current study was to investigate the role of a novel risk stratification system (RSS) for PSCCE. Methods: The study included patients with PSCCE attending any of five medical institutions in China in 2008–2021, four of which served as a training set (n = 422) for construction of the RSS while the other served as a separate cohort (n = 256) for validation of the model. The RSS was established based on covariates associated with overall survival (OS) with a two-sided P-value of < 0.05 in multivariable regression. Survival discrimination of RSS was assessed. Results: In the training cohort, multivariate regression analysis revealed age, Eastern Cooperative Oncology Group score, and initial lymph node metastasis to be independent prognostic factors for OS in non-distant metastatic PESCC; concurrent hepatic metastasis was the only significant predictor of distant metastatic PESCC. Accordingly, the RSS was developed and could classify patients into four subgroups: low-risk localized disease (LLD, defined as non-distant metastasis PESCC without risk factors, n = 58); high-risk localized disease (HLD, defined as non-distant metastasis PESCC with ≥ 1 risk factor, n = 199); low-risk metastatic disease (LMD, defined as metastatic PESCC without concomitant liver metastases, n = 103); and high-risk metastatic disease (HMD, definded as metastatic disease with synchronous liver metastases, n = 63). Three-year OS rates were 52.5%, 29.5%, 14.4%, and 5.7% for LLD, HLD, LMD, and HMD, respectively. When compared with the tumor-node-metastasis (TNM) system, RSS showed a consistently superior ability to predict OS in both the training and validation cohorts. Conclusion: The RSS is a reliable stratification model that could be used to optimize treatment for PESCC.

BackgroundPredicting the intracranial efficacy of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains challenging. The objective of this study was to construct a habitat-peritumoral radiomics framework for immunotherapy response prediction, concurrently identifying the optimal peritumoral extent.MethodsThis retrospective multicenter study analyzed 378 NSCLC-BM patients receiving PD-1/PD-L1 inhibitors. Participants were stratified into training (n=146), internal validation (n=63), and two external test cohorts (test 1: n=57; test 2: n=112). Logistic regression was conducted to determine significant clinical predictors. Habitat subregion segmentation was performed using K-means clustering with peritumoral extensions at incremental distances (1, 2, and 3 mm). Predictive models were developed using radiomic features extracted from intratumoral cores, habitat subregions, and peritumoral zones through machine learning approaches. A combined model integrated habitat signatures, peritumoral features, and clinical predictors. Model performance assessment employed the area under the curves (AUCs), calibration curves, and decision curve analyses (DCA).ResultsThe habitat-based XGBoost model demonstrated superior predictive performance across all cohorts compared to alternative models, achieving AUCs of 0.900 (training), 0.886 (internal validation), 0.820 (test 1), and 0.804 (test 2). For peritumoral analysis, the peri-1 mm RandomForest model exceeded other regional configurations. Integrating peri-1 mm features and clinical factors yielded a marginal performance enhancement in the combined model, with corresponding AUCs of 0.898, 0.894, 0.837, and 0.814. The combined model demonstrated optimal calibration and significant clinical utility, as evidenced by calibration curves and DCA.ConclusionThe validated habitat-peritumoral radiomics framework, optimized at a 1-mm peritumoral extent, demonstrates robust predictive accuracy for intracranial immunotherapy response in NSCLC-BM patients and offers significant clinical utility.

This open-label, single-arm phase II study assessed the safety and efficacy of sequential hypofractionated radiotherapy (RT) followed by zimberelimab and R-GemOx (rituximab, gemcitabine, oxaliplatin) in patients with primary refractory diffuse large B-cell lymphoma (DLBCL). Fourteen patients were enrolled between June 2022 and December 2023, with 13 included in the analysis. RT doses of 36 and 24 Gy were delivered to the gross and target volumes in 12 fractions, followed by zimberelimab and R-GemOx. The overall response rate within the irradiated field was 92.3%, and a complete response (CR) was achieved by 61.5% of patients; however, 38.5% experienced disease progression. Treatment-related toxicities were manageable, primarily comprising mild leukocytopenia. Digital spatial profiling revealed 53 differentially expressed genes in CD20-rich lymphoma regions and 93 in CD3-rich T cell regions in non-CR patients. Reactome analysis identified key immune system pathways. T cell infiltration correlated with treatment efficacy, and multiplex immunohistochemistry validated immune pathways as potential therapeutic targets. This study demonstrated the promising role of RT combined with immunochemotherapy in refractory DLBCL and suggests immune pathways as critical targets to improve treatment outcomes.

Tumor vascular normalization (TVN) is associated with antitumor therapeutic efficacy in nasopharyngeal carcinoma (NPC). However, the short time window of TVN is the biggest hindrance to its wide clinical application. We investigated whether targeting transforming growth factor beta can enhance the TVN effect of bevacizumab (BEV)-induced patient-derived xenograft (PDX) models of NPC. We constructed mouse subcutaneous PDX models of NPC and classified the mice into four drug-treatment groups, namely placebo control, galunisertib, BEV, and galunisertib + BEV. We performed MRI multi-parameter examinations at different time points and evaluated the vascular density, vascular structure, and tumor hypoxia microenvironment by histopathology. The efficacy of chemotherapy and drug delivery was evaluated by administering cisplatin. We found that combined therapy with galunisertib and BEV significantly delayed tumor growth, enhanced the TVN effect, and improved chemotherapeutic efficacy compared with monotherapy. Mechanistically, galunisertib reversed the epithelial-mesenchymal transition process and inhibited the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor by downregulating LAMC2. Correlation analysis of MRI data and pathological indicators showed that there was a good correlation between them.

BACKGROUND:Due to individual differences in tumors and immune systems, the response rate to immunotherapy is low in lung adenocarcinoma (LUAD) patients. Combinations with other therapeutic strategies improve the efficacy of immunotherapy in LUAD patients. Although radioimmunotherapy has been demonstrated to effectively suppress tumors, the underlying mechanisms still need to be investigated.METHODS:Total RNA from LUAD cells was sequenced before and after radiotherapy to identify differentially expressed radiation-associated genes. The similarity network fusion (SNF) algorithm was applied for molecular classification based on radiation-related genes, immune-related genes, methylation data, and somatic mutation data. The changes in gene expression, prognosis, immune cell infiltration, radiosensitivity, chemosensitivity, and sensitivity to immunotherapy were assessed for each subtype.RESULTS:We used the SNF algorithm and multi-omics data to divide TCGA-LUAD patients into three subtypes. Patients with the CS3 subtype had the best prognosis, while those with the CS1 and CS2 subtypes had poorer prognoses. Among the strains tested, CS2 exhibited the most elevated immune cell infiltration and expression of immune checkpoint genes, while CS1 exhibited the least. Patients in the CS2 subgroup were more likely to respond to PD-1 immunotherapy. The CS2 patients were most sensitive to docetaxel and cisplatin, while the CS1 patients were most sensitive to paclitaxel. Experimental validation of signature genes in the CS2 subtype showed that inhibiting the expression of RHCG and TRPA1 could enhance the sensitivity of lung cancer cells to radiation.CONCLUSIONS:In summary, this study identified a risk classifier based on multi-omics data that can guide treatment selection for LUAD patients.

Background:Almost all patients with small cell lung cancer (SCLC) relapse. The therapeutic options of relapsed SCLC are limited, and the clinical outcomes are poor. Thus, genomic profiling of relapsed SCLC patients may help to develop more effective therapeutic options.Methods:We collected blood specimens and follow-up information from a consecutive cohort of 31 patients diagnosed with relapsed SCLC in Zhongnan Hospital, Wuhan University, between 2018 and 2019, to analyze the comprehensive genomic profiling, and to investigate the impact of genomic alterations on therapeutic options and survival.Results:In our cohort of relapsed SCLC, the median number of genomic alterations was 5 (range, 1-11) per sample. The majority of patients were defined as low tumor mutation burden (TMB; 83.9%) and microsatellite stability (MSS; 87.1%). Immune checkpoint inhibitors (ICIs)-based treatment still brought considerable progression-free survival (PFS; 4.93-20.27 months) for patients with low TMB and MSS. Additionally, the most frequent genetic alterations observed in relapsed SCLC were TP53 (77%) and RB1 (52%). Other genomic alterations of high frequency were breast cancer 2 (BRCA2) (32%), ataxia telangiectasia mutated (ATM) (13%), epidermal growth factor receptor (EGFR) (10%), Notch receptor 1 (NOTCH1) (10%), and Fanconi anemia complementation group A (FANCA) (10%), in turn. Finally, based on the survival of therapeutic strategies targeting potential mutation genes, the role of genotyping in relapsed SCLC was confirmed.Conclusions:Our studies first exhibited comprehensive genomic profiling of relapsed SCLC, identifying several candidate genes, and briefly analyzed the association of survival and genomic alterations. Our data from a small cohort of relapsed SCLC will benefit further exploration the potential targets or biomarkers.

The success of immune checkpoint blockade has reaffirmed the importance of the immune system in cancer treatment. Immunotherapy enables the body's own immune system to fight tumor cells. However, the complex tumor microenvironment and its interaction with the immune system remain a mystery. The efficacy of immunotherapy is often affected by tumor heterogeneity. Molecular imaging techniques, such as single photon emission computed tomography and positron emission tomography, enable noninvasive whole‐body imaging of tumor and immune cell signatures. Noninvasive molecular imaging can also be used to monitor the treatment response of tumors, thereby achieving personalized response assessment, which may ultimately lead to improved clinical management, development of individualized treatments, and reliable prognosis. This article reviews recent research in immunotherapy response assessment, immune T‐cell imaging, immune checkpoint imaging, and radiomics/radiogenomics in immunotherapy. To date, these studies have primarily comprised exploratory preclinical imaging with preliminary results indicating that biomarker molecular imaging may have a role to play in the assessment of immunotherapy. Therefore, the principle of selecting patients for immunotherapy based on imaging results is feasible.

Trousseau's syndrome is a relatively rare reported event in immunotherapy-related clinical trials, mostly occurring in the early period of immune checkpoint inhibitor (ICI) therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. The patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.

Background The accumulation of reactive oxygen species (ROS) in tumor microenvironment (TME) is an important player for tumorigenesis and progression. We aimed to explore the outcomes of ROS on tumor vessels and the potential regulated mechanisms. Methods Exogenous H 2 O 2 was adopted to simulate the ROS setting. Immunofluorescence staining and ultrasonography were used to assess the vascular endothelial coverage and perfusions in the tumors inoculated with Lewis lung cancer (LLC) and melanoma (B16F10) cells of C57BL/6 mice, respectively. ELISA and western-blot were used to detect the expression of secreted acidic and cysteine-rich protein (SPARC) and Caveale-1 in human umbilical vein endothelial cells (HUVEC) extra- and intracellularly. Intracellular translocation of SPARC was observed using electron microscopy and immunofluorescence approaches. Result Under the context of oxidative stress, the pericyte recruitment of neovascularization in mouse lung cancer and melanoma tissues would be aberrated, which subsequently led to the disruption of the tumor vascular architecture and perfusion dysfunction. In vitro, HUVEC extracellularly SPARC was down-regulated, whereas intracellularly it was up-regulated. By electron microscopy and immunofluorescence staining, we observed that SPARC might undergo transmembrane transport via caveale-1-mediated endocytosis. Finally, the binding of SPARC to phosphorylated-caveale-1 was also detected in B16F10 tissues. Conclusion In the oxidative stress environment, neovascularization within the tumor occurs structural deterioration and decreased perfusion capacity. One of the main regulatory mechanisms is the migration of extracellular SPARC from the endothelium to intracellular compartments via Caveolin-1 carriers.

Background: The target definition of consolidation radiotherapy (RT) for extensive stage small-cell lung cancer (ES-SCLC) has not been standardized. This study aimed to demonstrate the feasibility of post-chemotherapy based consolidation RT in ES-SCLC.Methods: All ES-SCLC patients without initial brain metastases who completed >= 4 cycles of systemic therapy at Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University from 2012 to 2021 were included in this retrospective study. We correlated the site of first recurrence to the post-chemotherapy-based radiation volume (small-field). Relapse pattern, progression-free survival (PFS) and overall survival (OS) were compared between those received and did not receive consolidation RT.Results: A total of 152 patients were followed up for a median of 31.7 months (interquartile range [IQR], 23.9- 39.6 months). The median PFS and OS of the cohort were 8.3 months (IQR, 6.1-11.2 months) and 16.2 months (IQR, 9.9-24.9 months), respectively. Thoracic consolidation RT served not only as an independent prognostic factor for improved PFS in the entire cohort, but also significantly prolonged OS in the subgroup without syn-chronous liver metastases. Small-field consolidation RT markedly reduced in-field recurrences (hazard ratio [HR], 0.28 [95% CI, 0.12-0.38]; P < 0.001) without increasing out-of-field recurrences (HR, 0.40 [95% CI, 0.13-1.16]; P = 0.080). No relapse was observed at the margin of the targets. Treatment-related toxicities were moderate, with grade 3 acute radiation pneumonia, radiation esophagitis, and bone marrow suppression rates of 8.3%, 3.1%, and 12.5%, respectively. No grade 5 toxicity occurred.Conclusion: Small-field consolidation RT based on post-chemotherapy volume is safe and can significantly im -prove local control in ES-SCLC.

3001 Background: BL-B01D1 is a first-in-class novel ADC consisting of an EGFRxHER3 bispecific antibody linked to a novel TOP-I inhibitor payload via a cleavable linker. We now present safety/efficacy results from a FIH phase I study of BL-B01D1. Methods: This study included patients (pts) with locally advanced or metastatic solid tumors. For dose escalation (D-ESC, i3+3), BL-B01D1 was administered intravenously at doses of 0.27, 1.5, 3.0 mg/kg QW, 2.5, 3.0, 3.5mg/kg D1D8 Q3W or 4.5, 5.0, 6.0 mg/kg D1 Q3W. A subset of pts were enrolled into dose-expansion (D-EXP) at Q3W regimens. Results: As of Dec 31, 2022, 150 pts were enrolled and received at least one dose (D-ESC, n=25; D-EXP, n=125). DLTs were neutropenia, febrile neutropenia and thrombocytopenia at 3.0mg/kg QW and 3.5mg/kg D1D8 Q3W. The MTDs were determined to be 3.0mg/kg D1D8 Q3W and 6.0mg/kg D1 Q3W. D-EXP was carried out at 2.5, 3.0mg/kg D1D8 Q3W and 4.5, 5.0, 6.0 mg/kg D1 Q3W. 144 pts were enrolled across all Q3W dose levels (D-ESC and D-EXP), including 89 NSCLC, 7 SCLC, 27 nasopharyngeal cancer (NPC), 19 HNSCC and 2 others. Most common TRAEs (>10%, all grade / ≥ G3) were leukopenia (60%/30%), neutropenia (51%/34%), anemia (45%/15%), thrombocytopenia (44%/19%), alopecia (30%/0%), nausea (29%/<1%), vomiting (28%/0%), asthenia (21%/<1%), decreased appetite (22%/<1%), asthenia (21%/<1%), hypophagia (16%/0%), diarrhoea (15%/2%), mouth ulceration (15%/<1%), rash (13%/0%). No ILD was observed. 122 pts were evaluable for efficacy (at least 1 tumor assessment). PK and other details will be updated in the meeting. Conclusions: BL-B01D1 demonstrated encouraging efficacy in heavily pretreated metastatic/locally advanced solid tumors, especially in pts with EGFRm NSCLC. The safety profile showed adequate safety and tolerability. Clinical trial information: NCT05194982 . [Table: see text]

Polyfluoroalkyl substances (PFASs) are persistent pollutants that may cause breast cancer. However, associations between exposure to PFASs and the risk of breast cancer are controversial. We retrieved studies on the association between PFASs-perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS)-and breast cancer risk in women from PubMed, Embase, and the Web of Science. The pooled odds ratios (ORs) or relative risks (RRs) and their 95% confidence intervals (CIs) were extracted or calculated from provided data. Moreover, subgroup and metaregression analyses were performed to distinguish the potential sources of heterogeneity between studies. Lastly, eight original studies were included in the meta-analysis. PFOA and PFHxS were positively correlated with breast cancer risk, and the pooled ORs (and 95% CIs) were 1.32 (1.19 and 1.46) and 1.79 (1.51 and 2.11), respectively. PFNA was negatively correlated with breast cancer risk and the pooled OR (and 95% CIs) was 0.76 (0.6 and 0.96), and PFOS was shown to have no correlation with breast cancer risk and the pooled OR (and 95% CIs) was 1.01 (0.87 and 1.17). All results were merged in a random-effects model with significant heterogeneities (I-2 > 90%, p < 0.001). The results demonstrated that PFASs might be potential risk factors for breast cancer, and the compounds in low exposure levels could have a more harmful impact on human health.

Background: The role of postoperative radiotherapy (PORT) in resected stage IIIa-N2 non-small cell lung cancer (NSCLC) patients who have received adjuvant chemotherapy remains controversial. This study aimed to explore the value of PORT and determine which patients could benefit from PORT. Methods: Stage IIIa-N2 NSCLC patients treated with surgery and adjuvant chemotherapy were identified from the Surveillance, Epidemiology and End Results (SEER) databases from 2004 to 2015. Eligible patients were divided into the following two groups: PORT group and non-PORT group. Overall survival (OS) was estimated by the Kaplan-Meier (KM) method, and differences in survival were evaluated with log-rank test. Long-term cause-specific mortality consisted of lung cancer-related mortality and non-lung cancer-related mortality was investigated through competing risk analysis. Cox regression analysis was performed to identify variables that significantly affected OS. Results: We identified 2,347 eligible patients, after propensity score matching (PSM), 877 pairs were selected. Overall, there was no significant difference in OS between two groups, but the patients who received PORT had a lower lung cancer-related mortality rate. Subgroup analysis showed that PORT was associated with a significantly better OS and lower lung cancer-related mortality rate in patients with T2, grade I-II and positive/resected lymph node ratio (LNR) >= 0.31. The non-lung cancer-related mortality of PORT group was higher in the patients with squamous cell carcinoma, although the difference was not significant. The independent prognostic factors for OS were age, sex, grade, histology, the American Joint Committee on Cancer (AJCC) T stage and LNR. Conclusions: Our results revealed that PORT appears to be the optimal treatment strategy in patients with AJCC T2, grade I-II and LNR >= 0.31. PORT may not be recommended for patients with squamous cell carcinoma.

PurposeTo evaluate the outcomes of immune checkpoint inhibitor (ICI)-based treatments versus classical chemotherapy for metastatic non-small cell lung cancer (NSCLC) patients who develop epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance and to explore the population that may benefit from ICI-based therapy.Materials and methodsAll patients who had previously received EGFR-TKI therapy at two cancer centers in China and developed resistance to targeted therapies were included. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of the study cohort.ResultsA total of 132 patients were included. The median follow-up time for this cohort was 21.7 months (IQR, 14.8–28.8 months), calculated from the date of EGFR-TKI resistance. The median PFS and OS were 4.9 months (IQR, 2.8–9.2) and 13.5 months (IQR, 6.6–26.5 months), respectively. Multivariate analysis showed that ICI-based therapy could significantly improve OS when compared to the classic chemotherapy (hazard ratio [HR], 0.55; 95% CI, 0.34–0.88; P = 0.01) after adjusting for variables such as gender, age, mutation status, and brain or liver metastasis status. The combined modality of ICI plus chemotherapy could offer a long-term OS benefit in most subgroups, such as young (<65 years) patients, and those without secondary T790M mutations or absence of liver and brain metastases, and the populations with good Eastern Cooperative Oncology Group (ECOG) scores.ConclusionFor patients presenting with EGFR-TKI resistance, ICI-based therapy could offer a more favorable survival than classical chemotherapy. The combination of ICI with chemotherapy may be the optimal modality for those with good ECOG PS scores.

With the widespread use of immune checkpoint inhibitors (ICI), there is growing concern about reports of immune-related adverse events (irAE). In clinical practice, patients who experience severe toxicities by ICI-based therapies would require utmost caution in resuming ICI therapy because of the potential risk of serious irAEs caused by the reintroduction of immunotherapy. In this study, we report a case of recurrent endometrial cancer patient with PD-L1 positive as well as dMMR suffering from immunotherapy-associated myocarditis after first-line treatment with ICI combined with a multi-targeted anti-angiogenic agent. After symptomatic treatment, the patient was in complete remission from treatment toxicities. Subsequently, through MDT discussions, we selected a new PD-1 agent, zimberelimab, for rechallenge therapy, and the patient achieved a sustained disease remission without any treatment-related toxicities. To date, the manner and timing of the ICI re-challenge has been a subject of iterative deliberation. We believe that our experience could shed some light on ICI rechallenge therapy, and we look forward to more literatures to refine the ICI rechallenge scenarios.

Therapeutic radiation can result in substantially different survival outcomes for patients with non-small cell lung cancer (NSCLC). Measures for identification of patients who can benefit most throughout radiotherapy remain limited. In this retrospective study, survival analysis was performed based on a discovery cohort from TCGA and a validation cohort from three independent hospitals. Tumor mutational burden (TMB) and chromosomal aneuploidy (ANE) were derived from the whole exome sequencing (WES) data from treatment-naïve tumors. Integrated risk scores were derived from TMB and ANE by a multivariate Cox proportional hazards model. TCGA reveal that TMB and ANE are associated positively and negatively, respectively, with survival throughout radiotherapy. Additionally, the synergistically predictive significance of these two genomic alterations, in differing responders and non-responders to radiotherapy is identified. These biomarkers may have clinical potential to improve personalized treatment management by rationally identifying highly likely responders to therapeutic radiation in patients with NSCLC.

Background Intensity-modulated radiotherapy (IMRT) is widely applied during the treatment of esophageal squamous cell carcinoma (ESCC), but the optimal radiation dose still lacks a consensus. The aim of this study was to explore the optimal radiation dose for inoperable locally advanced ESCC patients treated with IMRT in a real-world clinical setting. Methods A total of 90 inoperable ESCC patients with locally advanced stages of Ⅱ-IVA treated with IMRT in our institute between February 1, 2014 and June 30, 2019 were included in this retrospective study. Sixty patients had received > 60 Gy (high dose group) and 30 patients had received ≤ 60 Gy (low dose group). The median radiation dose was 66 Gy (range: 61–70 Gy) and 50.2 Gy (range: 40–60 Gy), respectively. Concurrent chemotherapies were platinum-based regimens. Results The median progression free survival (PFS) and overall survival (OS) of all patients were 7.6 and 14.1 months, respectively. Patients in the high dose group exhibited a significantly better PFS (1-year PFS 34.6% vs 22.8%; 2-year PFS 11.9% vs 0%, P = 0.008) and OS (1-year OS 57.5% vs 39.5%; 2-year OS 31.4% vs 15.8%, P = 0.007). The median PFS in the high and low dose groups were 8.1 and 6.1 months, and the median OS were 15.4 and 8.5 months, respectively. Multivariate Cox analysis showed that radiation dose (> 60 Gy vs ≤ 60 Gy) was independently prognostic factor for OS (HR: 0.44; 95% CI: 0.22–0.89; P = 0.021), but not for PFS (HR: 0.56; 95% CI: 0.31–1.02; P = 0.058). There was no significant difference in treatment-related toxicities of grade ≥ 3 between the 2 groups (P = 0.402). Conclusion This retrospective study confirmed that higher radiation dose (> 60 Gy) resulted in better survival outcomes for inoperable patients with locally advanced ESCC treated with IMRT.