Clinical observation of anti-PD-1/PD-L1 immunotherapy plus concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

ImportanceLocally advanced, unresectable esophageal squamous cell carcinoma (ESCC) has a poor prognosis despite definitive chemoradiotherapy (CRT), and no standard maintenance therapy currently exists. Personalized vaccines targeting tumor neoantigens combined with immune checkpoint inhibitors may enhance antitumor immunity, potentially improving these patients’ outcomes.ObjectiveTo evaluate whether maintenance therapy with a personalized neoantigen dendritic cell vaccine (Neo-DCVac) combined with camrelizumab improves overall survival (OS) compared to camrelizumab alone in patients with unresectable locally advanced ESCC following definitive CRT.Design, setting, and participantsThe CHANT-241 trial is a randomized, open-label, single-center, phase 2 clinical trial enrolling 165 patients aged 18 to 80 years with histologically confirmed unresectable locally advanced ESCC. Eligible participants must have completed definitive chemoradiotherapy (CRT) and undergone radiologic assessment within 3 to 5 weeks demonstrating no evidence of disease progression. Prior immunotherapy is allowed. Additional inclusion criteria include the ability to provide fresh tumor tissue or archived pathology slides of sufficient quality. Patients are randomized in a 2:1 ratio to receive either combination therapy or camrelizumab alone.InterventionPatients in the experimental group receive Neo-DCVac (0.5–2 × 107 cells per dose, subcutaneously, following cyclophosphamide pretreatment), administered as 5 priming doses and 10 booster doses over a 12-month vaccination period, in combination with camrelizumab (200 mg intravenously every 4 weeks). Patients in the control arm receive camrelizumab alone at the same dose and schedule.Main outcomes and measuresThe primary endpoint is the 2-year OS rate. Secondary endpoints include OS, progression-free survival (PFS), treatment-related adverse events (TRAEs), and exploratory biomarker analyses, including tumor mutational burden (TMB), PD-L1 expression, and circulating tumor DNA (ctDNA).ResultsClinical outcomes are not yet available. Upon completion of enrollment and data analysis, the study findings will be disseminated through publication in a peer-reviewed journal.ConclusionsThe CHANT-241 trial is designed to evaluate whether the addition of Neo-DCVac to camrelizumab as maintenance therapy improves survival outcomes in patients with unresectable locally advanced ESCC. The findings aim to provide high-level evidence supporting a novel precision immunotherapy approach in this population.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT06675201.

Immune Checkpoint Inhibitor Therapy for Advanced, Unresectable Esophageal Squamous Cell Carcinoma: A Series of Patient-level Meta-analyses From Phase III Trials.

We report the case of a 70-year-old man with unresectable esophageal squamous cell carcinoma who achieved durable marked response with combined immune checkpoint inhibitor (ICI) therapy following radiotherapy (RT) alone. The patient presented with dysphagia and stridor due to a bulky esophageal tumor and cervical lymph node metastasis compressing the trachea. He was diagnosed with cT3N1M0 (Stage IIIB; 8th edition of the TNM classification) or cT4(101R-Trachea)N1M0 (Stage IVA; 12th edition of the Japanese classification). He underwent RT alone (total dose, 50 Gy), resulting in substantial tumor shrinkage and improvement in Eastern Cooperative Oncology Group performance status from 4 (due to ventilator dependence) to 1. Following confirmation of programmed death-ligand 1 positivity (tumor proportion score ≧ 1%), treatment with nivolumab (anti-programmed cell death-1 antibody) and ipilimumab (anti-cytotoxic T-lymphocyte antigen-4 antibody) was initiated. The therapeutic effect was remarkable, and treatment continued for 14 courses until an immune-related adverse event of secondary adrenal insufficiency interrupted therapy. Thereafter, there was no apparent recurrence on imaging for 31 months after treatment initiation. This case highlights the potential effect of RT followed by ICI combination therapy. Preclinical and clinical data suggest that prior RT may enhance systemic tumor immune responses. This therapeutic approach is currently being prospectively evaluated in the ongoing Phase II trial by the Japan Clinical Oncology Group (JCOG2311).

Polymeric micellar paclitaxel, cisplatin, and tislelizumab as first-line therapy for advanced unresectable esophageal squamous cell carcinoma: A phase II study with resistance profiling in poor responders.

Patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) face limited treatmentoptions and poor outcomes. Preclinical evidence supports chemoimmunotherapy as a conversion therapy; therefore, this study aims to evaluate the efficacy and safety of preoperative camrelizumab with paclitaxel and nedaplatin. Patients received a combination of camrelizumab (200 mg), paclitaxel (155 mg/m2), and nedaplatin (80 mg/m2) every 3 weeks. An efficacy assessment was performed every two cycles using the RECIST v1.1 criteria, and patients in the resected group underwent surgery 4-6 weeks after the last dose. The primary endpoint was 1-year overall survival (OS) rate, while secondary endpoints included surgical conversion rates, pathological response rates, objective response rate (ORR), disease-free survival (DFS), and safety. This trial enrolled 141 patients with unresectable ESCC (132 locally advanced [M0], 9 metastatic [M1]) with a median follow-up of 32.2 months. Post-induction ORR was 56.7%. The intention-to-treat (ITT) conversion rate reached 48.9% overall and 50.0% (66/132) in M0 patients (R0: 100%; pathological complete response (pCR): 20.9%; major pathological response: 55.2%). One-year OS was 78.7%. Surgical conversion significantly improved survival overall (median OS: not reached (NR) vs. 14.1 months; hazard ratio (HR) = 0.22; 95% CI, 0.13-0.37; P < 0.0001), with further benefit in objective responders (median OS: NR vs. 20.9 months; HR = 0.30; 95% CI, 0.14-0.61; P < 0.001). Approximately 75.9% of patients experienced treatment-related adverse events (TRAEs), predominantly mild to moderate. Pan-lactylation levels were significantly elevated in non-pCR ESCC compared to pCR tissues. A peritumoral radiomic features-derived model effectively stratified patients into distinct groups with significantly different OS and DFS. The chemoimmunotherapy regimen shows promising efficacy as a conversion therapy in improving surgical resectability and survival outcomes with manageable TRAEs, and does not delay surgery. ChiCTR2100046355.

ObjectiveTo evaluate the efficacy and safety of the sequential strategy involving induction chemoimmunotherapy followed by radiotherapy for locally advanced unresectable esophageal squamous cell carcinoma (ESCC), and to explore the optimal timing for radiotherapy intervention and the potential clinical benefits of subsequent consolidative immunotherapy.MethodThis study retrospectively collected clinical data from treatment-naïve patients with unresectable T1-4N0-3M0 stage ESCC who underwent induction chemoimmunotherapy followed by radiotherapy at the Affiliated Hospital of North Sichuan Medical College between December 2021 and May 2024. Patients were stratified into two cohorts: the early radiotherapy cohort (early-RT, n=34), who initiated radiotherapy after completion of 1–2 cycles of induction chemoimmunotherapy, and the late radiotherapy cohort (late-RT, n=44), who initiated radiotherapy after completing 3–6 cycles of induction chemoimmunotherapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety serving as the secondary endpoint.ResultWith a cutoff date of May 31, 2025, the median follow-up duration was 25.9 months. In the overall population, the median PFS was 16.0 months (95% confidence interval [CI], 11.7-20.3) and the median OS was 25.0 months (95%CI, 21.49-28.51). PFS was significantly longer in the early-RT cohort than in the late-RT cohort(20.4 vs. 13.7 months; HR = 0.53; p = 0.032). No statistically significant difference in OS was observed between the two cohorts (26.6 vs. 24.8 months; p = 0.728). Subsequent consolidative immunotherapy significantly improved PFS (median not reached [NR] vs. 12.8 months; HR = 0.46; p = 0.011) and OS (NR vs. 24.1 months; HR = 0.43; p = 0.017). In terms of safety, most treatment-related adverse events (TRAEs) were grade 1 or 2 in severity and were manageable. The incidence of toxicities did not differ significantly between the early-RT and late-RT cohorts (p > 0.05).ConclusionIn patients with unresectable locally advanced ESCC, the combination of early radiotherapy intervention and subsequent consolidative immunotherapy may represent a potential preferred therapeutic strategy. The findings from this study provide a rationale for the design of phase III clinical trials.

BackgroundTo address the heterogeneity in treatment responses and the lack of robust prognostic tools for unresectable esophageal squamous cell carcinoma (ESCC) patients undergoing immunochemotherapy, this study aimed to develop and validate an interpretable machine learning (ML) model for survival prediction and risk stratification.MethodsA retrospective cohort of 323 unresectable ESCC patients treated with immunochemotherapy (2019–2025) was analyzed. Using the XGBoost algorithm, we integrated baseline clinical features (age, tumor location, TNM stage) and laboratory parameters (albumin, globulin, blood glucose) to construct a prognostic model. SHapley Additive exPlanations (SHAP) values were employed to quantify feature contributions, and external validation (n=48) was performed to assess generalizability. SHAP (SHapley Additive exPlanations) is a game theory-based framework that enables model interpretability by quantifying the contribution of each feature to predictions. The primary endpoint was overall survival (OS).ResultsThe model achieved AUC values of 0.794 (internal test) and 0.689 (external test), with calibration curves demonstrating strong concordance between predicted and observed survival rates. Key prognostic factors included tumor response, age, hypoalbuminemia, hyperglobulinemia and hyperglycemia. Risk stratification using a nomogram-derived cutoff (total score ≥50) revealed significantly inferior 2-year OS in high-risk versus low-risk patients (21.3% vs 58.6%, P<0.001).ConclusionThis interpretable ML model effectively predicts survival outcomes in unresectable ESCC patients receiving immunochemotherapy, offering a data-driven tool for personalized therapeutic decision-making. Multicenter prospective trials are warranted to validate its clinical utility.

PD-1/PD-L1 inhibitors in advanced, unresectable esophageal squamous-cell carcinoma: A meta-analysis of their effects across patient subgroups.

Precision medicine for esophageal squamous cell carcinoma (ESCC) has not been implemented owing to a lack of site-specific therapeutic markers and biomarkers. We hypothesized that the genomic background of each subsite of the esophagus might be different, allowing us to develop site-specific treatment strategies (cervical, upper thoracic, middle thoracic and lower thoracic). This was a single-center retrospective cohort study. Patients diagnosed with ESCC who underwent comprehensive genomic profiling (CGP) at Keio University Hospital between April 2017 and March 2024 were recruited. Genomic profiles were analyzed and compared across esophageal subsites. Among the 107 patients with ESCC who underwent CGP, 6 were cervical, 16 were upper thoracic, 54 were middle thoracic, and 31 were lower thoracic. The most frequently altered genes were TP53, followed by CDKN2A and NFE2L2. The frequency of NFE2L2 mutations was significantly higher in the middle thoracic region (P = 0.041). The mutation rate increased from Stage I to IV (P = 0.0046). NFE2L2 mutations were rarely observed in early-stage cancers, suggesting that they may subsequently be acquired during growth and metastasis. Furthermore, a significant association was observed between a history of heavy alcohol consumption and NFE2L2 mutations. The overall survival of patients with unresectable or metastatic ESCC harboring NFE2L2 mutations was 12.0months, compared to 29.7months in patients without the mutations (HR: 2.37, P = 0.047). NFE2L2 mutations were more common in the middle thoracic esophagus, appeared to be associated with tumor progression, and were linked to poor prognosis.

ObjectiveTo investigate the predictive value of inflammation-based prognostic scores (IBs) on overall survival (OS) in elderly unresectable esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy (RT) or chemoradiotherapy (CRT).MethodsThis retrospective study included 120 elderly ESCC patients who received RT/CRT. IBs, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and systemic immune response index (SIRI), were calculated within one week before treatment and within two weeks after treatment.ResultsA total of 120 patients were included. The median age was 76 years. Significant differences were found between survivors (n=29) and non-survivors (n=91) in tumor size (p=0.018), T stage (p=0.006), and pre-treatment lymphocyte count (p=0.002). At the study endpoint, 75.8% of patients (91/120) had died, and 24.2% (29/120) remained alive. The median overall survival (OS) and progression-free survival (PFS) were 18 months and 15 months, respectively. The 1-year, 3-year, and 5-year OS rates were 61.7%, 18.3%, and 5.8%, respectively, and the corresponding PFS rates were 40.8%, 7.5%, and 1.7%. Pre-treatment NLR, SIRI, and SII were associated with OS. Post-treatment NLR and PLR were also predictors. However, in multivariate analysis, only age (p=0.002) and adverse events (p=0.003) remained independent predictors of OS.ConclusionHigh NLR, SII, and SIRI before treatment, and NLR and PLR after treatment, were associated with poorer OS in elderly ESCC patients undergoing RT/CRT. However, none of these IBs remained independent predictors in multivariate analysis, suggesting that their prognostic value may be influenced by confounding factors.

Conversion therapy, defined as curative-intent surgery or chemoradiotherapy after induction therapy, is gaining attention in patients with initially unresectable esophageal squamous cell carcinoma due to adjacent organ invasion (cT4b) or distant metastasis (M1). This systematic review aimed to assess survival outcomes, treatment strategies, and the evolving role of immune checkpoint inhibitors in this context. PubMed, Embase, and the Cochrane Library were comprehensively searched to identify studies published between 2010 and 2025 that reported conversion therapy outcomes in patients with esophageal squamous cell carcinoma with cT4b or M1. This review included 15 studies. A 2019 systematic review established the foundation for current practice in cT4b. Subsequent retrospective and prospective studies have reported 5-year overall survival rates of up to 51.6% in patients undergoing salvage or conversion surgery, with no residual tumor (R0) resection rates reaching 98.9% in extended procedures. The ongoing JCOG1510 phase III trial is expected to clarify the optimal strategy. Selected patients undergoing conversion surgery for M1 after induction therapy achieved a 5-year overall survival of 31.7%, with an R0 resection rate of 87%. Survival was not significantly associated with the metastatic site or treatment modality, highlighting the importance of treatment response and multidisciplinary decision-making. The incorporation of immune checkpoint inhibitors into induction regimens expands the pool of candidates eligible for curative-intent local therapy. Conversion therapy may provide durable survival in carefully selected patients, and further prospective studies are warranted to refine patient selection and establish standardized treatment algorithms.

Background/AimsThis retrospective analysis examined the efficacy and safety of combined endostatin and definite chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma.MethodsThe current study was a retrospective analysis of esophageal squamous cell carcinoma patients treated with endostatin combined with definitive chemoradiotherapy. The patients received induction chemotherapy or concurrent chemotherapy. The endostatin dose was 30 mg/d from days one to five of each induction cycle. During concurrent therapy, the endostatin dose was 30 mg/d concomitant with radiotherapy at 60–68 Gy delivered in 2.0–2.2 Gy/d fractions.ResultsThe objective response and disease control rates were 82.76% and 84.48%, respectively. The one-year, two-year, and three-year overall survival rates were 91.83%, 86.43%, and 73.86%, respectively. The one-year, two-year, and three-year progress-free survival rates were 74.09%, 62.16%, and 61.95%, respectively. The most common grade 3 and 4 adverse events were esophagitis (31.03%), anemia (12.07%), pneumonia (12.07%), leukopenia (10.34%), neutropenia (8.62%) and thrombocytopenia (8.62%).ConclusionsA combination of endostatin with definite chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma achieved high response rates, progress-free survival rates, and overall survival rates. The toxicity was acceptable. Nevertheless, additional prospective randomized controlled clinical trials will be needed to confirm the superiority of this treatment strategy.

BackgroundThe clinical value of immune checkpoint inhibitors (ICIs) in the treatment of unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains under investigation in large-scale randomized clinical trials. In this study, we aimed to assess the efficacy and safety of concurrent ICIs in combination with definitive chemoradiotherapy (dCRT) in a relatively large cohort of patients with unresectable LA-ESCC.MethodsBetween January 2019 and December 2023, this retrospective study included patients with LA-ESCC who received ICIs concurrently with dCRT at Jiangsu Cancer Hospital. The primary endpoints were overall survival (OS) and progression-free survival (PFS), while secondary endpoints included clinical response and safety.ResultsA total of 165 patients with LA-ESCC were included in this study, with a median age of 66 years (IQR 60–70 years), and 163 (98.8%) had stage III or IVA disease. After a median follow-up of 24 months (IQR 16–33 months), the 2-year OS was 64.3% (95%CI 57.2%-72.3%), and the 2-year PFS was 50.2% (95%CI 42.9%-58.8%). It is noteworthy that induction therapy before dCRT did not improve OS (HR = 1.09, 95% CI: 0.61–1.93, P = 0.770) or PFS (HR = 1.00, 95% CI: 0.59–1.72, P = 1.000). The objective response rate (ORR) was 70.9% and disease control rate (DCR) was 86.7%. The most common adverse event was grade 3 or worse lymphopenia, observed in 60.0% of the patients (90/165).ConclusionICIs combined with concurrent dCRT demonstrated promising efficacy and manageable safety in patients with unresectable LA-ESCC.

The combination of anti-programmed death-1 (PD-1) inhibitors and chemotherapy is the standard first-line treatment for unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, real-world data remain limited, particularly regarding prognostic biomarkers. This multi-institutional retrospective study analyzed patients with metastatic or unresectable ESCC who received first-line pembrolizumab or nivolumab plus fluoropyrimidine and platinum-based chemotherapy. Treatment regimens mirrored those in KEYNOTE-590 and CheckMate 648. Efficacy, safety, and prognostic factors were assessed. Prognostic factors were identified using multivariable Cox regression, and a point-based risk scoring system was developed. Among 87 patients, the objective response rate was 48.3%, and the disease control rate was 77.0%. Median progression-free survival (PFS) was 5.6 months (95% CI, 4.5-8.7), and the median overall survival (OS) was 13.1 months (95% CI, 10.6-not reached). Grade 3-4 treatment-related adverse events occurred in 51.7% of patients. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2, elevated C-reactive protein, and lower programmed death-ligand 1 (PD-L1) combined positive score (CPS) were independently associated with worse PFS and OS. A prognostic risk score ranging from 0 to 5 based on these factors stratified patients into four prognostic groups with distinct survival outcomes. Median PFS ranged from not reached in the low-risk group to 2.1 months in the high-risk group. Stratifying PD-L1 CPS into three levels (<10, 10-49, ≥50) revealed a graded association between CPS and treatment outcomes, supporting the need for more nuanced PD-L1 evaluation beyond binary classification. First-line anti-PD-1 therapy combined with chemotherapy demonstrated favorable real-world outcomes in ESCC. The proposed prognostic scoring system may help personalize treatment strategies.

The prognosis for patients with esophageal squamous cell carcinoma (ESCC) is poor, with a 5-year survival rate of approximately 30%. There are significant differences in prognosis among patients, and some patients experience local recurrence and distant metastasis within 1 year after comprehensive treatment. Therefore, there is an urgent need for highly sensitive and specific biomarkers to assess the therapeutic risks and prognosis of patients with inoperable esophageal cancer. This study aimed to investigate the predictive value of the LabBM score in the survival of patients with inoperable ESCC. A single-center retrospective study was conducted, including 150 and 155 patients with unresectable ESCC who received concurrent chemoradiotherapy at our hospital between January 1, 2013, and June 30, 2018, and between July 1, 2018, and March 1, 2020, respectively, as the training and validation cohorts. Laboratory parameters, including lactate dehydrogenase, platelet count, C-reactive protein, and albumin, were collected 1 week prior to concurrent chemoradiotherapy. The LabBM score was calculated, and survival differences were analyzed across patients with different LabBM scores. Cox regression and Kaplan–Meier analyses were used to assess factors influencing progression-free survival (PFS) and overall survival (OS), aiming to clarify the prognostic value of the LabBM score for PFS and OS. In the training group, of the 150 patients enrolled, 123 were in the low LabBM group (0–1), 23 in the medium LabBM group (1.5–2), and 4 in the high LabBM group (2.5–3.5). The median survival was 33 months in the low LabBM group, 11 months in the medium LabBM group, and 6.5 months in the high LabBM group, with a significant difference in survival between the 3 groups (P = .000). Univariate Cox analysis showed that a higher LabBM score was associated with worse OS (P < .05). Multivariate Cox regression analysis revealed that a higher LabBM score (hazard ratios: 2.75, 95% CI: 1.08–7.03, P = .034) was an independent influencing factor for OS. In receiver operating characteristic analysis, the AUC area for OS and PFS predicted by the LabBM-based risk model was 0.92 (95% CI: 0.86–0.97, P = .00) and 0.956 (95% CI: 0.88–0.98, P = .000), respectively. The AUC for LabBM scores predicting OS and PFS were 0.63 (95% CI: 0.54–0.72, P = .011) and 0.61 (95% CI: 0.52–0.70, P = .039), respectively. The AUC area of the risk model was significantly higher than that of other single parameters. Subsequently, we re-enrolled 155 patients with inoperable esophageal cancer in different time periods for the above analysis, and the results were consistent with the experimental group. In inoperable ESCC patients, the LabBM score-based risk model is a novel and effective prognostic indicator.

2094O SKYSCRAPER-07: A phase III, randomised study of atezolizumab (atezo) with or without tiragolumab (tira) in patients (pts) with unresectable esophageal squamous cell carcinoma (ESCC) that has not progressed following definitive concurrent chemoradiotherapy (dCRT)

Abstract Background The prognosis of locally advanced borderline resectable esophageal squamous cell carcinoma (BR-ESCC) and unresectable esophageal squamous cell carcinoma (UR-ESCC) is poor. Induction therapy makes it possible for downstaging of tumor to have a opportunity of radical resection, thus improving the prognosis. However, the optimal induction therapy remains under exploration, and the prognostic value of conversion surgery remains controversial. Methods This was a retrospective study of patients with BR-ESCC and UR-ESCC who received chemotherapy (group CT), chemoradiotherapy (group CRT) and immunochemotherapy (group ICT) as the initial induction therapy. Based on induction therapy effect, patients received treatment with surgery (group ST), non-surgical treatment (group NST) and non-treatment (group NT). The outcomes included initial imaging efficacy, adverse events (AEs) of initial induction therapy and overall survival (OS). Results The objective response rate (ORR) of the primary tumor lesions, ORR of the lymph nodes with a maximum short axis &amp;gt; 1.0 cm, tumor downstaging rate and the potential R0 resection rate after initial induction therapy were 49.7%, 36.4%, 40.0% and 54.1%, respectively. ICT group showed significantly higher lymph node ORR vs. CT/CRT (P = 0.015), with numerically higher primary tumor ORR and downstaging (P &amp;gt; 0.05). Grade 3+ AE rates were comparable across groups (P &amp;gt; 0.05). Post-induction potential R0-resectable ESCC patients in ST group had superior OS vs. NST (P = 0.007); no OS difference in others (P = 0.271). Conclusion ICT is superior to CT and CRT in terms of induction efficacy and the three exhibit similar incidence rates of adverse reactions. Treatment modalities involving conversion surgery are recommended in patients with potential R0 resectable ESCC after induction therapy. Non-surgical treatment is still a better option for the others.

Abstract Background Esophageal squamous cell carcinoma (ESCC) presents a considerable clinical challenge, particularly in cases deemed unresectable due to cT4b tumors or bulky lymphadenopathy. Traditional treatment modalities predominantly consist of radical chemoradiotherapy. The USE-1 study aims to evaluate the clinical efficacy and safety of conversion therapy that combines chemotherapy and immunotherapy to potentially convert unresectable ESCC to a resectable state. Methods Preoperative therapy comprised sintilimab, nab-paclitaxel, and cisplatin administered every three weeks for 2–4 cycles. Following two cycles of immunochemotherapy, the initial efficacy evaluation was conducted; Patients receiving four cycles of immunochemotherapy who did not meet the criteria for esophagectomy were excluded from the study. Surgery was conducted 3–6 weeks after the completion of the preoperative therapy. The primary endpoint was the conversion rate, while secondary endpoints included R0 resection rate, pathologic complete response (pCR) rate, major pathological response (MPR) rate, perioperative complications and recurrence-free survival (RFS), overall survival (OS). Results 25 qualifying patients had been enrolled (17 with cT4b tumors and 8 with bulky lymphadenopathy). Esophagoaortic fistula occurred in 1 case, and esophagotracheal/esophagobronchial fistula occurred in 2 cases. Ultimately, 14 patients underwent thoraco-laparoscopic esophagectomy without intraoperative conversion to open surgery (9 with cT4b tumors and 5 with bulky lymphadenopathy). R0 resection was achieved in 64.3% of these patients (9/14), with pCR and mPR rates of 28.6% (4/14) and 14.3% (2/14), respectively. No postoperative deaths were reported. The median follow-up time was 13.2 months (0.9–22.4 months), with a median PFS of 9.2 months and a median OS of 11.3 months. Conclusion Esophagectomy following conversion immunochemotherapy appears to be a promising radical treatment for unresectable esophageal squamous cell carcinoma. The conversion rate was 56% (14/25), with R0 resection achieved in 64.3% (9/14) of patients. Long-term follow-up results are necessary for further elucidation of the treatment’s efficacy.

Abstract Background This study investigated the efficacy and safety of camrelizumab in combination with paclitaxel and nedaplatin as preoperative therapy for patients with unresectable esophageal squamous cell carcinoma (ESCC). We also examined the tumor microenvironment through habitat radiomics to evaluate its potential for predicting treatment response. Methods This single-arm, phase II study enrolled patients with clinically confirmed unresectable ESCC (staged T2–4, Nany, M0/M1). Participants received camrelizumab (200 mg) with paclitaxel (155 mg/m2) and nedaplatin (80 mg/m2) every three weeks. Efficacy was assessed every two cycles to evaluate operability. Endpoints included overall survival (OS) at 12 months, pathological complete response (pCR) rates, objective response rate (ORR), disease control rate (DCR), and disease-free survival (DFS). We also utilized retrospective clinical data as training set and the patient data of this study as test set to extract radiomic features from the tumor and its surrounding environment. Results Among 134 patients analyzed, the overall ORR was 56.7%. The surgical conversion rate was 48.9%. In a pathological analysis of 67 patients, the pCR rate was 20.9%, and the major pathological response (MPR) rate was 55.2%. The median OS for all patients was 30.7 months, and 12.8 months for non-surgical patients. The median OS for surgical patients has not been reached, but significantly higher than OS of non-surgical patients. The median DFS for surgical patients has not been reached. Adverse events occurred in 75.9% of patients. A model integrating intratumoral and peritumoral habitat radiomics with clinical variables effectively predicted pCR. Conclusion The combination of camrelizumab, paclitaxel, and nedaplatin demonstrates promising efficacy and manageable adverse effects as a conversion therapy, enhancing surgical resectability and survival outcomes without delaying surgery.