This study aims to examine the recurrence patterns in patients with locally advanced esophageal squamous cell carcinoma who underwent surgery following neoadjuvant chemotherapy combined with immunotherapy. Retrospective analysis of patients with esophageal squamous cell carcinoma who received neoadjuvant Chemo-IO before surgery at Zhejiang Cancer Hospital between 2019 and 2023. The clinicopathological features, recurrence patterns, overall survival (OS), and disease-free survival (DFS) were analyzed, and the impact of postoperative adjuvant radiotherapy on prognosis was evaluated. In total, 422 patients were included in the study. After a median follow-up of 22 months, disease recurrence was observed in 89 (21.1%) patients, comprising 37 cases (8.8%) of locoregional recurrence, 30 cases (7.1%) of distant metastasis, and 22 cases (5.2%) of combined recurrence. Patients who achieved a pathologic complete response demonstrated significantly higher 3-year OS rates (90.0% vs. 72.5%; P = 0.01) and DFS rates (73.2% vs. 61.8%; P = 0.046). Univariable and multivariable analyses identified pathological lymph node staging (ypN0 vs. ypN+; HR: 1.73; 95% CI: 1.01-2.99; P = 0.047) as an independent prognostic factor for locoregional recurrence. Kaplan-Meier curves for OS and DFS demonstrated that postoperative radiotherapy (PORT) significantly improved OS and DFS in ypN+ patients after propensity score matching. Additionally, PORT significantly enhanced locoregional recurrence-free survival and distant recurrence-free survival in ypN+ patients. In patients receiving neoadjuvant Chemo-IO, locoregional recurrence is the predominant recurrence pattern. For ypN+ patients, PORT significantly improved survival outcomes. However, long-term outcomes require further investigation through randomized controlled trials.

The association of neoadjuvant chemoimmunotherapy (NCIT) vs chemoradiotherapy (NCRT) with tumor downstaging and survival in locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear because of limited evidence.

To compare the associations of NCIT and NCRT with tumor regression and long-term survival in patients with locally advanced ESCC.

In this comparative effectiveness research study, from January 2016 to March 2023, patients with locally advanced ESCC who underwent esophagectomy following NCRT or NCIT were identified from a prospective database of 8 high-volume esophageal surgery centers in China. Follow-up began on the date of surgery and continued until the last recorded contact or March 2024, whichever occurred first. Data were analyzed between April and September 2024.

The primary end points were 2-year overall survival (OS) and disease-free survival (DFS). Secondary end points included major pathologic response (MPR) and pathologic complete response (pCR). Cox proportional hazard regression analysis was used to investigate the risk factors for OS and DFS.

The study included 1428 patients (median [IQR] age, 63 [57-68] years; 1184 men [82.9%]), with 704 patients in the NCRT group and 724 patients in the NCIT group. After propensity score matching, there were 532 patients in each group. The 2-year OS (81.3% vs 71.3%; hazard ratio, 1.57; 95% CI, 1.26-1.96; P < .001) and DFS (73.9% vs 63.4%; hazard ratio, 1.37; 95% CI, 1.11-1.69; P < .001) rates were significantly higher in NCIT group than in the NCRT group. The NCRT group had a higher MPR rate than that of the NCIT group (71.8% vs 61.5%), whereas the pCR rates were similar (25.9% vs 22.9%). Multivariable Cox analysis demonstrated that NCIT and MPR were independently associated with both OS and DFS. The NCIT group exhibited a lower overall recurrence rate (126 patients [23.7%] vs 190 patients [35.7%]) and distant metastasis rate (72 patients [13.5%] vs 133 patients [25.0%]), although locoregional metastasis rates were similar (98 patients [18.4%] vs 111 patients [20.9%]). Better OS and DFS were obtained for the NCIT group than for the NCRT group, regardless of whether adjuvant immunotherapy was given.

Compared with NCRT, patients with locally advanced ESCC receiving NCIT had better 2-year OS and DFS. The decrease in distant metastasis may be the main reason, but further prospective randomized clinical trials are needed to verify this finding.

Neoadjuvant immunochemotherapy is expected to become the standard treatment mode for locally advanced esophageal squamous cell carcinoma (ESCC). This study aims to analyze the clinical outcomes and long-term survival of neoadjuvant immunochemotherapy for locally advanced ESCC, and explore the feasibility of using major pathological response (MPR) as a surrogate endpoint.

This real-world retrospective study consecutively included eligible patients with stage II-IVA locally advanced ESCC who received neoadjuvant immunochemotherapy and surgery between 2019 and 2022 at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine.

This study collected a total of 166 patients, and ultimately included 126 patients after screening. The objective response rate (ORR) was 69.8% (88/126). The incidence of grade 3-4 adverse events (AEs) was 13.5% (17/126). MPR was observed in 49 (38.9%) patients, and 24 (19.0%) patients achieved a complete pathological response (pCR). The median progression-free survival (PFS) was 31.7 months and the 3-year PFS rate was 56.3%. The median overall survival (OS) was not reached and the 3-year OS rate was 70.6%. The median PFS of the non-MPR group was 25.0 months, with the MPR group not achieved (hazard ratio [HR], 2.503; 95% CI 1.359-4.610; P = 0.0022). The median OS in the non-MPR group was 31.7 months and not reached in the MPR group (HR, 3.607; 95% CI 1.576-8.254; P = 0.0012). MPR is an independent prognostic factor affecting OS (HR, 2.522; 95% CI 1.018-6.401; P = 0.046).

Neoadjuvant immunochemotherapy is safe and effective for locally advanced ESCC, and can result in certain survival benefits. MPR can serve as a surrogate endpoint for predicting long-term OS.

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive form of esophageal cancer, particularly prevalent in East Asia. This study aimed to investigate the impact of sex on clinical outcomes, including survival and postoperative complications, in elderly ESCC patients following esophagectomy.

We conducted a retrospective cohort study using data from the Sichuan Cancer Hospital & Institute Esophageal Cancer Case Management Database, involving patients aged 70 years and older who underwent esophagectomy from May 2016 and August 2021. Patients were grouped by sex, and subgroup analyses were performed on non-smoking, non-drinking patients. OS and DFS were analyzed using the Kaplan-Meier method, and between-group comparisons were conducted using the log-rank test. Propensity score matching (PSM) was applied to adjust for potential confounders.

Although females showed a longer median OS (60.2 months) compared to males (40.0 months), the difference was not statistically significant after PSM (HR = 0.885, P = 0.573). Similarly, no significant differences were observed in DFS between sexes. In non-smoking, non-drinking subgroups, OS and DFS remained higher but without significant sex-based differences. Postoperative adverse events such as pulmonary infection and anastomotic leakage were common across groups.

While sex does not significantly affect OS and DFS in elderly ESCC patients, male patients may experience higher rates of certain postoperative complications, such as abnormal liver function and pneumothorax.

The treatment of cancer has brought about a paradigm shift with the introduction of immune checkpoint blockade (ICB) therapy, which is mostly dependent on inhibiting PD-1/PD-L1 and CTLA-4. However, recent studies have shown limited efficacy of this treatment in esophageal squamous cell carcinoma (ESCC). Preliminary studies have found that tifcemalimab (the world's first anti-BTLA blocking monoclonal antibody) combined with toripalimab (PD-1) and chemotherapy has shown favorable safety and efficacy in several solid cancers. This study aimed to evaluate the safety and efficacy of neoadjuvant tifcemalimab combined with toripalimab and chemotherapy following esophagectomy for resectable ESCC, and the association of adjuvant immunotherapy with improved survival outcomes.

Patients with pathologically confirmed cT1b-3N1-3M0 or cT2-3N0M0 thoracic ESCC were treated with neoadjuvant tifcemalimab (200mg, iv, d1) in combination with toripalimab (240mg, iv, d1) and chemotherapy (paclitaxel 135-175 mg/m2, d1 + cisplatin 75 mg/m2, d1) every 3 weeks for 2 cycles. Patients undergoing esophagectomy with pathological complete response (pCR) were administered up to 15 cycles of adjuvant tifcemalimab (200 mg) and toripalimab (240 mg), whereas patients without pCR received tifcemalimab in combination with toripalimab and adjuvant chemotherapy for 2 cycles, followed by tifcemalimab in combination with toripalimab immunotherapy up to 13 cycles. The patient with incomplete resection was decided to receive radiotherapy after a multidisciplinary consultation. The primary endpoint of this study was the pCR rate. The secondary endpoints include major pathological response rate (MPR), objective response rate (ORR), disease control rate (DCR), adverse events, R0 resection rate, event-free survival (EFS), and overall survival (OS).

The Ethics Committee of Henan Provincial People's Hospital has approved the protocol (No 2024-132-03). This study is the world's first prospective clinical trial to evaluate the safety and efficacy of the BTLA inhibitor in combination with PD-1 and chemotherapy as neoadjuvant/adjuvant therapy for locally advanced thoracic ESCC. We predicted that perioperative combination immunotherapy as a potentially preferred and effective treatment strategy may lead to better survival outcomes.

The optimal time interval from neoadjuvant immunotherapy combined with chemotherapy to surgery for esophageal squamous cell carcinoma remains unknown. This research aims to assess the impact of time interval on pathological response and survival prognosis.

Esophageal squamous cell carcinoma patients receiving neoadjuvant immunotherapy combined with chemotherapy followed by esophagectomy between January 2021 and March 2024 were included. The pathological response, survival outcomes, surgical outcomes, and postoperative complications were compared between the timely surgery group (time interval ≤ 6 weeks) and the delayed surgery group (time interval > 6 weeks).

A total of 133 cases were included in this research. The pathological complete response (pCR) rates in timely surgery group and delayed surgery group were 23.4% and 12.8% (P = 0.167). There were no statistically significant differences between the two groups in terms of anastomotic fistula (P = 0.321), pulmonary infection (P = 0.427), chylothorax (P = 0.502), multiple organ dysfunction syndrome (P = 0.206), operation time (P = 0.359), blood loss (P = 0.093), number of resected lymph nodes (P = 0.091), hospital stay (P = 0.167), and R0 resection rate (P = 0.523). The 3-year overall survival (OS) rates were 77.5% in timely surgery group, and 63.5% in delayed surgery group (P = 0.046). The 3-year disease-free survival (DFS) rates were 59.1% and 38.4% in the two groups, respectively (P = 0.037). Additionally, multivariate Cox regression analyses indicated that the time interval from immunochemotherapy to surgery was independent prognostic factor for both OS (P = 0.049) and DFS (P = 0.025).

Prolonged time interval from neoadjuvant immunotherapy combined with chemotherapy to surgery did not improve pCR rate and was associated with worse OS and DFS in esophageal squamous cell carcinoma.

We aimed to explore the efficacy and safety of neoadjuvant toripalimab plus chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (ESCC).

This phase II, non-randomized, 2-cohort study enrolled patients with unresectable, stage T1-4N0-3M0-1 ESCC (M1 only includes patients with lymph node metastasis in the supraclavicular region). Patients received neoadjuvant therapy comprised of albumin-bound paclitaxel, nedaplatin and toripalimab every 3 weeks, for 2 cycles, followed by CCRT (total dose 60Gy in cohort A, 50Gy in cohort B, combined with oral capecitabine). The primary endpoint was progression-free survival (PFS). The trial is registered with ClinicalTrials.gov, NCT04844385.

Between February 26, 2021 and June 20, 2023, 124 patients were enrolled, and 118 (95.2%) patients completed treatment. The objective response rate to neoadjuvant chemo-immunotherapy was 91.9% overall, and was 93.7% in cohort A-60Gy and 93.4% in cohort B-50Gy after CCRT. With a median follow-up of 30.8 months, the 18-month PFS rates were 65.0% (95% CI, 53.9-78.3%) in cohort A-60Gy and 65.1% (95% CI, 53.7-78.8%) in cohort B-50Gy. Grade (G) 3 and G5 pneumonitis occurred in two (3.2%) and one patient (1.6%) in cohort A-60Gy, respectively, with no ≥G3 pneumonitis in cohort B-50Gy. Improvements on patient reported outcomes from baseline to 12 months post-CCRT were observed overall.

Neoadjuvant chemo-immunotherapy, radiotherapy and concurrent capecitabine achieved promising efficacy in locally advanced ESCC. Further investigation is warranted.

None.

Improving pathological complete response (pCR) rate is currently the main goal of neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, improved pCR rates do not consistently translate into better prognosis, likely due to regimen-specific pCR heterogeneity. We investigated this heterogeneity and potential biomarkers between two common neoadjuvant regimens.

We included 445 LA-ESCC patients from four centers, with 228 receiving neoadjuvant chemoradiotherapy (nCRT) and 217 undergoing neoadjuvant chemotherapy combined with immunotherapy (nICT). Propensity score matching ensured group comparability. We assessed pCR rates and their associations with overall survival (OS), disease-free survival (DFS), and recurrence patterns. Immune-related biomarkers were investigated through RNA sequencing and immune infiltration analysis, then validated via multiplex immunofluorescence staining.

Overall, pCR was associated with significantly higher DFS (HR = 0.3 [0.18-0.5], P < 0.01) and OS (HR = 0.19 [0.08-0.41], P < 0.01) compared to non-pCR. The nICT group had a lower pCR rate than the nCRT group (27.2% vs. 42.9%) but demonstrated comparable prognosis and reduced distant metastasis. Among pCR patients, DFS was significantly better in the nICT group (HR = 0.2 [0.05-0.86], P = 0.031), with a trend toward improved OS. Immune analysis revealed increased CD8 + T cell infiltration, particularly CD69 + CD8 + tissue-resident memory T cells (TRM), in the nICT pCR group. The proportion of CD69 + CD8 + TRM cells was significantly linked to improved DFS (P = 0.016) and OS (P = 0.015), suggesting they may be superior prognostic markers compared to pCR rates.

The pCR obtained from different neoadjuvant treatments has distinct prognostic outcomes. The CD69 + CD8 + TRM, as a potential prognostic predictor, warrants further investigation.

Accurate prediction of pathologic complete response (pCR) following neoadjuvant immunotherapy combined with chemotherapy (nICT) is crucial for tailoring patient care in esophageal squamous cell carcinoma (ESCC). This study aimed to develop and validate a deep learning model using a novel voxel-level radiomics approach to predict pCR based on preoperative CT images.

In this multicenter, retrospective study, 741 patients with ESCC who underwent nICT followed by radical esophagectomy were enrolled from three institutions. Patients from one center were divided into a training set (469 patients) and an internal validation set (118 patients) while the data from the other two centers was used as external validation sets (120 and 34 patients, respectively). The deep learning model, Vision-Mamba, integrated voxel-level radiomics feature maps and CT images for pCR prediction. Additionally, other commonly used deep learning models, including 3D-ResNet and Vision Transformer, as well as traditional radiomics methods, were developed for comparison. Model performance was evaluated using accuracy, area under the curve (AUC), sensitivity, specificity, and prognostic stratification capabilities. The SHapley Additive exPlanations analysis was employed to interpret the model's predictions.

The Vision-Mamba model demonstrated robust predictive performance in the training set (accuracy: 0.89, AUC: 0.91, sensitivity: 0.82, specificity: 0.92) and validation sets (accuracy: 0.83-0.91, AUC: 0.83-0.92, sensitivity: 0.73-0.94, specificity: 0.84-1.0). The model outperformed other deep learning models and traditional radiomics methods. The model's ability to stratify patients into high and low-risk groups was validated, showing superior prognostic stratification compared with traditional methods. SHAP provided quantitative and visual model interpretation.

We present a voxel-level radiomics-based deep learning model to predict pCR to neoadjuvant immunotherapy combined with chemotherapy based on pretreatment diagnostic CT images with high accuracy and robustness. This model could provide a promising tool for individualized management of patients with ESCC.

Esophagectomy is the primary treatment for localized esophageal squamous cell carcinoma (ESCC). Intraoperative thoracic duct ligation (TDL) has been suggested as an adjunct to reduce the risk of postoperative chylothorax in patients with ESCC, but its effect on long-term oncologic outcomes remains uncertain.

Data from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database were analyzed for patients treated between 2010 and 2017. Participants were classified into TDL and non-TDL groups. Univariate Cox regression analyses and propensity score matching (PSM) were used to identify independent risk factors for overall survival (OS).

A total of 2,510 patients were included, with 2,095 in the TDL group and 415 in the non-TDL group. The median follow-up was 63.97 months. No significant differences in OS were observed between the TDL and non-TDL groups (HR: 1.13; 95% CI: 0.96-1.31; P = 0.13). After PSM, the analysis continued to show no significant differences between the groups (P = 0.72).

Intraoperative TDL during esophagectomy did not significantly impact long-term OS in patients with ESCC.

To explore the recurrence pattern and risk factors associated with the relapse of thoracic esophageal squamous cell carcinoma (TESCC) among patients who received esophagectomy following neoadjuvant immunochemotherapy (NICT).

A total of 191 TESCC patients who received esophagectomy following NICT were retrospectively reviewed from 2019 to 2022. The first recurrence patterns were assessed. The postoperative recurrence-free survival (RFS) was determined using the Kaplan-Meier method. Multivariate recurrence risk factor analysis was performed using the logistic regression model.

As of the December 31, 2023 follow-up, 66 patients experienced recurrence, with a median time to recurrence of 10.8 months (1.2-37.3 months). The recurrence pattern included locoregional recurrence (LR), distant recurrence (DR), and LR + DR, accounting for 69.7 %, 16.7 %, and 13.6 %, respectively. Locoregional lymph node (LN) predominated the pattern of postoperative recurrence (40/66), particularly in the mediastinal station 2R (17.5 %) and 4R (16.5 %). The 2-year RFS rates for groups with dissected LN stations of ≤6, 7-9, and 10-14 were 50.5 %, 72.3 %, and 63.5 %, respectively (P = 0.04). Similarly, the 2-year RFS rates for groups with dissected LNs of <15, 15-29, and ≥30 were 49.7 %, 61.6 %, and 71.6 %, respectively (P = 0.28). Furthermore, tumor length >5 cm, the T-stage evaluation as clinically stable disease, dissected LN stations ≤6, and the ypN2-3 stage were unfavorable factors for postoperative failure in patients.

The major pattern of LR may be LN recurrence after NICT in TESCC patients, particularly in the station 2R and 4R. In addition, less than 6 LN dissection stations or less than 15 LNs are not recommended.

Muscle-invasive urothelial carcinoma (MIUC) is a highly aggressive cancer associated with poor prognosis. Despite advancements in treatment, the optimal therapeutic approach remains unclear. Immune checkpoint inhibitors, when added to chemotherapy, have shown promise in improving patient outcomes.

This study aimed to evaluate the efficacy and safety of adjuvant tislelizumab combined with gemcitabine/cisplatin (Tisle+GC) compared to GC alone in patients with high-risk MIUC.

We conducted a retrospective analysis of 117 patients with histologically confirmed pT3/4 and pN+ MIUC treated at our center between October 2016 and March 2023. Eligible patients received either Tisle+GC or GC alone, excluding those with prior neoadjuvant therapy. We compared disease-free survival (DFS), overall survival (OS), and treatment-related adverse events (AEs) between the two groups using Cox proportional hazards models and Kaplan-Meier estimates.

The Tisle+GC group showed significantly longer median DFS (19.08 vs. 9.06 months, HR = 0.114, p < 0.001) and OS (20.07 vs. 10.63 months, HR = 0.083, p = 0.026) compared to the GC group. Nerve tract invasion was identified as a significant predictor of poor outcomes (HR = 22.1, p = 0.003). Both groups experienced manageable grade 1-2 immune-related AEs, with pruritus being the most common, followed by liver function abnormalities and thyroid disturbances. Nonhematologic toxicities in the Tisle+GC group included elevated aspartate aminotransferase and hyponatremia, while the GC group mainly reported vomiting. No treatment-related fatalities occurred.

The addition of tislelizumab to GC chemotherapy significantly improved both DFS and OS in high-risk MIUC patients. The safety profile was manageable, with immune-related AEs being predictable and not life-threatening. The findings support the potential of Tisle+GC as an effective adjuvant therapy.

Tisle+GC is a promising adjuvant treatment for high-risk MIUC, offering improved survival outcomes with a manageable safety profile. Further prospective studies are needed to confirm these results and establish the long-term benefits of this combination therapy.

Neoadjuvant chemoimmunotherapy emerged as a promising treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, a comparison of clinical outcomes with neoadjuvant chemotherapy was lacking.

To provide evidence supporting clinical decision-making for neoadjuvant chemoimmunotherapy in LA-SCCHN treatment.

Literature was retrieved from PubMed, Web of Science, Embase, and the Cochrane Library for studies on the efficacy and safety of neoadjuvant chemoimmunotherapy and chemotherapy in LA-SCCHN published before August 10, 2024. The study was registered in the PROSPERO (CRD42024573816).

A total of 28 clinical trials with 2021 patients were included. The neoadjuvant chemoimmunotherapy group had significantly higher pathologic complete response (pCR) (33 % vs. 18 %, P = 0.04) and partial response (PR) (65 % vs. 38 %, P < 0.01). No significant differences were found in overall survival (OS) (hazard ratio: 0.85, 95 % CI: 0.77-0.93) and progression-free survival (PFS) (hazard ratio: 0.72, 95 % CI: 0.61-0.86). Regarding safety outcomes, in the single-arm trials, grade 3-4 treatment-related adverse events (TRAEs) occurred in 14 % of the chemoimmunotherapy group and 13 % of the chemotherapy group, with grade 5 TRAEs at 0 % and 4 %, respectively, showing no significant difference (P = 0.80; P = 0.08). In both RCTs and non-RCT, chemoimmunotherapy had a higher Risk Ratio (RR) for grade 3-4 TRAEs (RR: 1.42, 95 % CI: 0.87-2.31).

Neoadjuvant chemoimmunotherapy has shown promising efficacy and safety for LA-SCCHN, but further randomized trials are needed to confirm long-term survival benefits.

Anaplastic thyroid carcinoma (ATC) is one rare type of thyroid carcinoma without standard systemic treatment for advanced disease. Recent evidence has demonstrated promising efficacy of immune checkpoint inhibitors, particularly those targeting programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), in a variety of solid tumors. However, there have been no research of immune checkpoint inhibitors plus chemotherapy in ATC. Here, we present the case of a 37-year-old man with metastatic ATC with positive PD-L1 expression, who achieved long-term remission of 34 months after later-line treatment with zimberelimab (a PD-1 inhibitor) and nab-paclitaxel, followed by single-agent zimberelimab maintenance therapy. After three cycles of the combination treatment, the thyroid lesion and the liver metastases shrank dramatically, leading to the best overall response of partial remission. PD-L1 expression may serve as a potential biomarker for tumor response to immune checkpoint inhibitors in ATC. Our review highlights the need for further studies investigating the role of PD-L1 status as biomarker to predict the prognosis of immunotherapy in the treatment of ATC.

Clinically, multimodal therapies are adopted worldwide for the management of cancer, which continues to be a leading cause of death. In recent years, immunotherapy has firmly established itself as a new paradigm in cancer care that activates the body's immune defense to cope with cancer. Immunotherapy has resulted in significant breakthroughs in the treatment of stubborn tumors, dramatically improving the clinical outcome of cancer patients. Multiple forms of cancer immunotherapy, including immune checkpoint inhibitors (ICIs), adoptive cell therapy and cancer vaccines, have become widely available. However, the effectiveness of these immunotherapies is not much satisfying. Many cancer patients do not respond to immunotherapy, and disease recurrence appears to be unavoidable because of the rapidly evolving resistance. Moreover, immunotherapies can give rise to severe off-target immune-related adverse events. Strategies to remove these hindrances mainly focus on the development of combinatorial therapies or the exploitation of novel immunotherapeutic mediations. Nanomaterials carrying anticancer agents to the target site are considered as practical approaches for cancer treatment. Nanomedicine combined with immunotherapies offers the possibility to potentiate systemic antitumor immunity and to facilitate selective cytotoxicity against cancer cells in an effective and safe manner. A myriad of nano-enabled cancer immunotherapies are currently under clinical investigation. Owing to gaps between preclinical and clinical studies, nano-immunotherapy faces multiple challenges, including the biosafety of nanomaterials and clinical trial design. In this review, we provide an overview of cancer immunotherapy and summarize the evidence indicating how nanomedicine-based approaches increase the efficacy of immunotherapies. We also discuss the key challenges that have emerged in the era of nanotechnology-based cancer immunotherapy. Taken together, combination nano-immunotherapy is drawing increasing attention, and it is anticipated that the combined treatment will achieve the desired success in clinical cancer therapy.

Neoadjuvant chemoimmunotherapy (NCIT) has improved pathological complete response and conferred survival benefits in patients with locally advanced esophageal cancer. However, surgical complications unrelated to the tumor continue to detract from patient outcomes. While the "watch-and-wait" strategy has been implemented in clinical complete responders following neoadjuvant therapy for rectal cancer, there is a lack of evidence supporting its practicability in esophageal cancer after NCIT. This pilot case series involves six clinical complete responders who deferred surgery under close surveillance after three or four cycles of neoadjuvant camrelizumab plus chemotherapy and who subsequently received camrelizumab as maintenance treatment. The primary observation measure of the series is event-free survival (EFS). Routine follow-up examinations included endoscopy, biopsy, contrast-enhanced computed tomography, and ultrasonography every 3-6 months. For patients who experienced local recurrence without metastasis, the salvage operation was the priority recommendation. As of September 5, 2024, the average follow-up duration was 124.4 weeks, with the average EFS reaching 134.7 weeks. No deaths or distant metastases were observed. Our findings suggest that responders to NCIT may be spared from esophagectomy. On the prerequisite of sufficient tumor regression during neoadjuvant cycles, immunotherapy may facilitate the continued eradication of residual disease in this series.

The present retrospective cohort study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy for resectable esophageal cancer and report the preliminary short-term survival.

A multicenter, retrospective study was conducted concerning patients who received neoadjuvant PD-1 agents plus platinum-based chemotherapy between January 2019 and January 2022. The primary endpoint was the tumor pathologic complete response (pCR) rate.

Two hundred and thirteen patients with initial stage cI-IVA esophageal cancer who received neoadjuvant immunochemotherapy were identified. The complete tumor resection(R0) rate was 99.1%. The pCR rate was 31.9%, and the overall major pathological response rate was 49.8%. The 2-year DFS rate was 78.9% (95% CI: 72.9-85.4%) and the 2-years OS rate was 80.9% (95% CI: 75.3-86.9%). The incidence of TRAEs and surgical complications rate were 68.5 and 35.2%, respectively.

The PD-1 agents combined with chemotherapy in the neoadjuvant treatment for resectable stage I-IVA esophageal cancer had a high pCR rate as well as good short-term survival benefits and tolerable toxicity.

Digestive system neoplasms are highly heterogeneous and exhibit complex resistance mechanisms that render anti-programmed cell death protein (PD) therapies poorly effective. The tumor microenvironment (TME) plays a pivotal role in tumor development, apart from supplying energy for tumor proliferation and impeding the body's anti-tumor immune response, the TME actively facilitates tumor progression and immune escape via diverse pathways, which include the modulation of heritable gene expression alterations and the intricate interplay with the gut microbiota. In this review, we aim to elucidate the mechanisms underlying drug resistance in digestive tumors, focusing on immune-mediated resistance, microbial crosstalk, metabolism, and epigenetics. We will highlight the unique characteristics of each digestive tumor and emphasize the significance of the tumor immune microenvironment (TIME). Furthermore, we will discuss the current therapeutic strategies that hold promise for combination with cancer immune normalization therapies. This review aims to provide a thorough understanding of the resistance mechanisms in digestive tumors and offer insights into potential therapeutic interventions.

Esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), is a major health concern worldwide, particularly in China. Surgical resection is still considered the primary curative treatment for this disease. However, the effect of different surgical methods-traditional hand-sewn anastomosis and modern mechanical anastomosis-remains controversial. A retrospective study was thus performed to elucidate how these two techniques affected the clinical prognosis of patients. Data were retrospectively collected from the comprehensive Esophageal Cancer Case Management Database of Sichuan Cancer Hospital and Institute (Chengdu, China), covering the period from 2010 to 2017. The cohort consisted of patients who underwent esophagectomy for ESCC, divided into two groups based on the suturing technique used: Manual suturing (MS) and mechanical suturing (MeS). A total of four causal inference methods for retrospective studies, namely inverse probability of treatment weighting, standardized mortality ratio weighting, overlap weighting and propensity score matching analysis, were used to minimize potential selection bias. The primary outcome evaluated was overall survival (OS), allowing for a direct comparison of the long-term efficacy of the two suturing methods. In a retrospective analysis of 2,510 patients undergoing esophagectomy, significant differences in OS were observed between the MeS group and the MS group (hazard ratio: 0.84; 95% confidence interval: 0.75-0.95; P=0.004). However, after matching or weighting based on causal inference analyses, no significant differences in survival outcomes between groups were obtained. The equivalence in outcomes suggests that either suturing method may be equally viable in clinical practice, offering flexibility in surgical decision-making without compromising OS.

Esophageal cancer has a poor prognosis and survival rate due to its high incidence in Asia, lack of early symptoms and limited treatment options. In recent years, many clinical trials have demonstrated that immunotherapy has greatly improved the survival of patients with esophageal cancer. In addition, the combination of neoadjuvant immunotherapy with other popular therapeutic regimens has shown good efficacy and safety. In this review, we summarize the progress of clinical trials and some breakthroughs in neoadjuvant immunotherapy for esophageal cancer in recent years and suggest the possibility of multimodal neoadjuvant immunotherapy regimens, as well as directions for future development.

This prospective study in a real-world setting investigated the feasibility and safety of S-1 plus nimotuzumab (S-1-Nimo) based concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients who failed to neoadjuvant chemotherapy or chemoimmunotherapy.

LA-ESCC patients who failed to converse to resectable disease after neoadjuvant chemotherapy or chemoimmunotherapy were enrolled to receive the 4-week S-1-Nimo regimen of radiotherapy (40 Gy in 20 fractions, 5 days per week), S-1 chemotherapy, and nimotuzumab. Then, after surgical assessments, patients evaluated as resectable disease received surgery; patients with unresectable disease continued to receive definitive radiotherapy (50-60 Gy in 25-30 fractions, 5 days per week) concurrently with S-1-Nimo. The primary endpoint was event-free survival (EFS).

Sixty-four patients were enrolled and evaluated. The median follow-up time was 23.2 months. Median EFS was 9.6 (95% confidence interval [CI], 7.1-14.0) months, with an estimated 2-year EFS rate of 24.2%. The median overall survival (OS) and the estimated OS rate at 2 years were 13.4 (95% CI, 10.3-17.5) months and 31.2%, respectively. Twelve underwent surgery, with a surgical conversion rate of 18.8% and an R0 resection rate of 100.0%. Subgroup analysis identified the significantly prolonged EFS and OS in patients who experienced radical surgery (median EFS, not reached vs. 8.7 months; p = .0117. median OS, 24.9 vs. 10.6 months; p = .0205) as compared to those treated with CCRT. Of 64 patients, grade 3 adverse events mainly included radiation esophagitis (4.7%), anemia (1.6%), and thrombocytopenia (1.6%).

The study demonstrated the reasonable efficacy and promising safety of the S-1-Nimo-based CCRT in LA-ESCC patients with failure to neoadjuvant chemotherapy or chemoimmunotherapy.

Esophageal squamous cell carcinoma is a prevalent and aggressive gastrointestinal tumor, particularly in East Asia. However, there is a lack of consensus on the long-term survival outcomes of intrathoracic anastomosis and cervical anastomosis following esophagectomy. This study aims to provide a comprehensive summary of the long-term survival outcomes of these 2 anastomosis techniques.

We employed data drawn from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database from January 2010 to December 2017. Patients were stratified into 2 distinct groups according to the anatomical location of anastomosis following esophagectomy: those who underwent intrathoracic anastomosis (IA) (IA group) and those who underwent cervical anastomosis (CA) (CA group). To account for potential confounding factors and baseline imbalances between the 2 groups, propensity score matching was employed.

The CA group exhibited longer overall survival compared with the IA group, with a median overall survival of 49.10 months versus 35.87 months (hazard ratio, 1.118; 95% CI, 1.118-1.412; P < .001). Additionally, survival rates at 1, 3, and 5 years were higher in the CA group (87%, 59%, and 48%, respectively) compared with the IA group (86%, 50%, and 39%, respectively). The significance persisted even after propensity score matching (hazard ratio, 1.164; 95% CI, 1.013-1.336; P < .001), inverse probability of treatment weighting, and overlap weighting were applied. The survival difference between CA and IA was attributed to varying extents of lymph node dissection, particularly in the upper mediastinal zone (P < .001).

Our study suggests that there could be the potential survival advantage of CA over IA in patients undergoing esophagectomy for esophageal squamous cell carcinoma.

To explore whether neoadjuvant Sintilimab is suitable for patients with gastroesophageal junction (GEJ) adenocarcinoma, we designed this study to evaluate the short-term efficacy and safety of neoadjuvant Sintilimab in combination with chemotherapy for resectable GEJ adenocarcinoma.

We retrospectively collected data on patients with GEJ adenocarcinoma who underwent surgery after receiving neoadjuvant immunotherapy combined with chemotherapy at Jining First People's Hospital between October 2020 and October 2023. The primary endpoint was complete pathological response (pCR) rate; secondary endpoints: major pathological response (MPR) rate, neoadjuvant therapy-related adverse events (AES), the safety of surgery, Postoperative Complications, and overall survival (OS).

24 eligible patients were enrolled in the study and achieved a pCR rate of 16.7%. The treatment-related AES was manageable. The median time interval between the end of neoadjuvant therapy and surgery was 35 days (28-81 days), R0 resection rate was 100%. The most common postoperative complications in the study were pneumonia (n = 11, 45.8%). Median follow-up was 13.5(interquartile range: 8.00, 25.50) months, Kaplan-Meier survival analysis showed median OS was not reached.

It was safe and effective for resectable GEJ adenocarcinoma to undergo neoadjuvant Sintilimab combined with chemotherapy followed by surgery, and long-term efficacy needs to be confirmed by further follow-up.

Adebrelimab is a humanized monoclonal antibody against programmed death-ligand 1 (PD-L1) and is also a novel immune checkpoint inhibitor, which has been used in the first-line treatment of extensive stage small cell lung cancer (SCLC) with its unique mechanism of action and good clinical efficacy. Significant progress has been made in the treatment of adebrelimab in other malignancies such as non-small cell lung cancer, triple-negative breast cancer, esophageal squamous cell carcinoma, and the treatment of SCLC at different stages is also being explored. Therefore, adebrelimab emerges as a promising new treatment option for patients with small cell lung cancer (SCLC) and other types of malignant tumors.

The application of neoadjuvant immunotherapy in the treatment of esophageal cancer needs further exploration. This study aimed to investigate the safety and effectiveness of tislelizumab, an anti-PD-1 antibody, combined with chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC).

In this phase II study, patients with clinical stages of II-IVA (T3-T4 and/or node positive) potentially resectable LA-ESCC were enrolled. Patients received neoadjuvant tislelizumab and chemotherapy every 3 weeks for 4 cycles before surgery and adjuvant tislelizumab for 9 months. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy.

The study included 30 patients. 25 patients completed neoadjuvant chemoimmunotherapy and underwent surgery, 96% with R0 resection. The pCR and MPR rate was 44% and 52%. The 6-month and 1-year DFS rate was 100% and 75.3%. 43.3% patients experienced severe (grade 3-4) treatment-related adverse events (TRAEs) and 5 patients developed severe immune-related adverse events (irAEs). Further exploration found that a group of peripheral lymphocyte subsets increased significantly after 2 cycles of neoadjuvant therapy in patients who achieved pCR, suggesting the importance of dynamic monitoring of circulating lymphocyte.

The combination of perioperative tislelizumab and neoadjuvant chemotherapy has achieved an encouraging pCR rate and demonstrated a manageable safety profile in patients with potentially resectable ESCC.

https://www.chictr.org.cn/, identifier ChiCTR2100043772.

This study reported the safety and efficacy of a phase 2, open-label, single-arm, exploratory clinical trial of induction immunochemotherapy in patients with initially unresectable advanced esophageal squamous cell carcinoma (ESCC).

Patients underwent three cycles of induction therapy with tislelizumab, cisplatin, and 5-fluorouracil. The primary endpoints were the safety, major pathological response (MPR), and pathological complete response (pCR). Secondary endpoints included the R0 resection rate, disease-free survival (DFS), and overall survival (OS). Genomic data and immune microenvironment data were analyzed exploratively.

The treatment was safe, with a grade 3 or higher adverse event rate of 14.9% (7/47). Of the total 47 patients enrolled in the study, 19 (40.4%) achieved MPR, 12 (25.5%) achieved pCR, 4 (8.5%) achieved complete clinical response (cCR) and declined surgery, and 23 (48.94%) underwent successful resection. Median follow-up was 18 months, with a median DFS of 24 months, a median OS of 36 months. A high tumor mutation burden was associated with a better prognosis for patients who underwent surgery. Patients who achieved pCR had higher levels of immune cell infiltration and a greater proportion and concentration of tertiary lymphoid structures compared with those who experienced a major pathological response.

Tislelizumab combined with chemotherapy is effective for ESCC, yielding high cCR, pCR, surgical conversion, and R0 resection rates, and tolerable adverse events.

NCT05469061.

Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy.

Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection.

Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815-1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447-1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40).

The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival.

This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC).

Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate.

Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS.

Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

The current treatment strategies for borderline resectable esophageal squamous cell carcinoma remain controversial. This study aimed to evaluate the efficacy and safety of programmed cell death 1 inhibitors combined with chemotherapy, followed by conversion surgery, for borderline resectable esophageal squamous cell carcinoma.

Patients with borderline resectable esophageal squamous cell carcinoma treated with induction immunochemotherapy from January 1, 2020 to July 1, 2023 at our hospital were retrospectively analyzed. The primary study outcome was the R0 resection rate. Secondary study outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission (pCR) rate, and safety.

Forty patients with borderline resectable esophageal squamous cell carcinoma were included in the analysis. The R0 resection rate was 23/40 (57.5%); the conversion success rate was 27/40 (67.5%), and the pCR rate was 11/40 (27.5%). The median follow-up was 23.6 months (95% CI, 19.1-28.2). One-year OS and PFS rates were 77.7% and 71.8%, respectively. The incidence rate of Grade 3-4 adverse events was 10%. There was a significant difference in PFS between patients who underwent surgery and those who did not (P = 0.008, HR: 0.144 95%CI: 0.034-0.606). However, the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063-1.416). Patients who achieved clinical downstaging after induction therapy had significantly better OS (P = 0.004 h: 0.110 95%CI: 0.025-0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026-0.426) compared to those who did not.

Conversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for borderline resectable esophageal squamous cell carcinoma.

Esophageal cancer (EC) is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in-depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody-drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.