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Background: Malignant esophageal mediastinal fistula is a severe complication that occurs in both the advanced stages of esophageal cancer and after radiotherapy for esophageal cancer. Esophageal mediastinal fistula is very susceptible to complications such as mediastinitis and mediastinal abscess, resulting in a significantly elevated mortality rate for patients. We reported a rare case of esophageal mediastinal fistula after immunotherapy for non-small cell lung cancer (NSCLC)., Case Presentation: A 74-year-old male patient with NSCLC was hospitalized in July 2023. About one week after Tislelizumab immunotherapy, the patient suddenly developed high fever accompanied by coughing and choking on water, chest tightness, shortness of breath, and hemoptysis. Following the completion of bronchial artery computed tomography angiography (CTA), imaging suggested the presence of esophageal mediastinal fistula. We opted for a conservative medical treatment instead of surgery. The patient was discharged without any complications., Conclusions: This is the first case of NSCLC accompanied by an esophageal mediastinal fistula after treatment with tislelizumab. The occurrence of malignant esophageal mediastinal fistula is very uncommon and poses a high level of hazard. In addition, this paper provides a concise overview of cases of lung cancer complicated with esophageal fistula in the past 10 years. It offers valuable insights for diagnosis and treatment, serving as a resource for clinicians., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol for this study was examined by the Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine. The participants expressed full knowledge of this report and signed an informed consent form, agreeing to publicly publish their personal clinical data, but not for any other purposes. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Blocking of the interaction between Programmed cell death 1 (PD-1) and its ligand PD-L1 by monoclonal antibodies has elicited unprecedented therapeutic benefits and achieved a major breakthrough in immunotherapy of multiple types of tumors. Here, we determined the crystal structure of PD-1 in complex with the Fab fragment of tislelizumab. This monoclonal antibody was approved in December 2019 by the China National Medical Product Administration for Hodgkin's lymphoma and is under multiple clinical trials in China and the US. While the three complementarity determining regions (CDRs) in the light chain are involved in the target interaction, only CDR3 within the heavy chain interacts with PD-1. Tislelizumab binds the front β-sheet of PD-1 in a very similar way as PD-L1 binds to PD-1, thereby blocking the PD-1/PD-L1 interaction with a higher affinity. A comparative analysis of PD-1 interactions with therapeutic antibodies targeting PD-1 provides a better understanding of the blockade mechanism of PD-1/PD-L1 interaction in addition to useful information for the improvement of therapeutic antibodies capable of diminishing checkpoint signaling for cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although concurrent Chemoradiotherapy (cCRT) is presently the standard intervention for patients with inoperable, locally advanced Esophageal Squamous Cell Carcinoma (ESCC), it has been associated with poor long-term survival outcomes. Notably, Immune Checkpoint Inhibitors (ICIs) improve the long-term survival of Esophageal Cancer (EC) patients, with manageable Adverse Effects (AEs). Herein, 90 patients with residual pathology after radical simultaneous Radiotherapy (RT) for inoperable/refused-to-operate ESCC were enrolled and randomized into two treatment groups (Chemotherapy+immunotherapy and chemotherapy alone) in a 2:1 ratio. This study will also discuss the value of immunotherapy in improving long-term survival outcomes in patients with pathological residuals after concurrent RT for locally advanced, inoperable ESCC. Clinical trial registration: http://www.chictr.org.cn/identifier is ChiCTR2200063345. [ABSTRACT FROM AUTHOR]

Background: 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). Methods: 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. Results: 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. Conclusions: 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. Clinical Trial Registration: https://www.chictr.org.cn/ , identifier ChiCTR2100043772. [ABSTRACT FROM AUTHOR]

Background: Alpha-fetoprotein-producing gastric cancer (AFPGC) represents a particularly aggressive subtype of gastric carcinoma characterized by elevated rates of vascular invasion, lymphatic dissemination, hepatic metastasis, and an unfavorable clinical outcome. Treatment strategies for AFPGC have historically lacked specificity. Herein, a case is presented involving AFPGC in which the patient exhibited a notable response to combined anti-PD-1 antibody immunotherapy and SOX chemotherapy, potentially achieving a cure. This report marks the first application of this regimen in neoadjuvant therapy for AFP gastric cancer, followed by radical resection and postoperative adjuvant therapy. Case summary: A 62-year-old male patient presented with persistent upper abdominal distension and discomfort lasting over 2 months. Initial investigations revealed markedly elevated serum alpha-fetoprotein (AFP) levels, and subsequent pathological examination confirmed the diagnosis of AFPGC via gastroscopy. Due to the patient's condition, surgical resection was initially deemed unfeasible. Therefore, a chemo-immunotherapy regimen consisting of SOX chemotherapy and the PD-1 inhibitor tislelizumab was administered for 3 cycles. Following this, successful laparoscopic radical gastrectomy was performed. The treatment protocol was continued with an additional 3 cycles postoperatively. At the time of this case report, the patient maintained a good quality of life with no evidence of disease recurrence or adverse events. Conclusion: The present report highlights a case of AFPGC where significant therapeutic success was achieved through a combined regimen of chemotherapy and immunotherapy, both before and after surgery. The use of anti-PD-1 antibody (tislelizumab) in combination with SOX regimen (S-1 and oxaliplatin) demonstrated effective treatment of AFPGC, potentially offering a curative approach. This approach represents a promising targeted therapy option for patients with AFPGC. [ABSTRACT FROM AUTHOR]

Extramammary Paget disease (EMPD) is a rare epithelial adenocarcinoma in apocrine-gland rich skin, involving the vulva, the scrotum, and the penis. with distant metastases and a poor prognosis. Local EMPD patients generally have a good prognosis, with expected 5-year survival of 60%–92%, but distant metastasis represents poor prognosis and 5-year survival of 10%. Treatment approaches for advanced EMPD are chemotherapy and biological agents, which carry limited efficacy. We report the case of a 57-year-old man diagnosed with metastatic EMPD, who showed a long-term disease control with a combination therapy (an immune checkpoint inhibitor - tislelizumab plus chemotherapy – paclitaxel albumin and cisplatin). This patient underwent a wide penile scrotal lesion excision and six cycles of tislelizumab plus chemotherapy. The patient achieved partial response for the metastatic lesions according to the Response Evaluation Criteria in Solid Tumors (version 1.1). This case report supports further investigation of the combination treatment of chemotherapy and immune checkpoint inhibitors in the management of metastatic EMPD, which currently has an abysmal prognosis and no standardized treatment. [ABSTRACT FROM AUTHOR]

Introduction: RATIONALE-301 (NCT03412773) was a global, phase 3 study comparing the efficacy and safety of tislelizumab with sorafenib as first-line (1L) treatment in adult patients with unresectable hepatocellular carcinoma (HCC) that met its primary endpoint of noninferiority in overall survival (OS). This analysis compared health-related quality-of-life (HRQOL) outcomes between the arms. Methods: Systemic therapy-naive adults with HCC were randomized 1:1 to receive tislelizumab (n = 342) or sorafenib (n = 332). HRQOL was assessed using EORTC QLQ-C30, QLQ-HCC18, and EQ-5D-5L. At cycles 4 and 6, a mixed model for repeated measures was performed using key-prespecified patient-reported outcome (PRO) endpoints of the QLQ-C30 and the QLQ-HCC18. Time to deterioration was analyzed with the Kaplan-Meier method using the PRO endpoints. Results: At cycles 4 and 6, patients in the tislelizumab arm had better HRQOL outcomes than the patients in the sorafenib arm per mean-change difference in GHS/QOL, QLQ-C30 physical functioning and fatigue, and QLQ-HCC18 symptom index; however, no differences for pain were observed. Patients in the tislelizumab arm had lower risk of deterioration in GHS/QOL (HR: 0.68; 95% CI: 0.49–0.94), QLQ-C30 physical functioning (HR: 0.45; 95% CI: 0.32–0.63) and fatigue (HR: 0.47; 95% CI: 0.36–0.61), QLQ-HCC18 symptom index (HR: 0.52; 95% CI: 0.34–0.81), and HCC-specific fatigue (HR: 0.59; 95% CI: 0.45–0.79). For pain, both arms had similar risk of deterioration (HR: 0.78; 95% CI: 0.56–1.09). At cycles 4 and 6, patients in the tislelizumab arm maintained in EQ-5D-5L visual analog scale, whereas scores decreased for the patients in the sorafenib arm. Conclusion: Patients with 1L HCC treated with tislelizumab had favorable HRQOL outcomes compared with patients treated with sorafenib, particularly in fatigue and physical functioning. These results, along with favorable safety profile, better response rate, and OS noninferiority, support tislelizumab as a potential 1L treatment option for unresectable HCC. [ABSTRACT FROM AUTHOR]

Pulmonary sarcomatoid carcinoma (PSC) is a scarce pathologic type of lung cancer of non-small cell lung cancer (NSCLC) that exhibits resistance to conventional chemotherapy and radiotherapy, resulting in a poor prognosis. Herein, a 67-year-old man was admitted to the hospital in January 2022 with a diagnosis of PSC for over 6 months and a newly discovered brain metastasis for 4 days. He had previously undergone two unsuccessful chemotherapy regimens: bevacizumab combined with pemetrexed and loplatin, and albumin-bound paclitaxel combined with loplatin. Radiotherapy was performed for the brain and skull metastases, followed by treatment with tislelizumab combined with anlotinib, a programmed cell death protein 1 (PD-1) inhibitor with anti angiogenic drug, respectfully. The patient initially received nine cycles of treatment with tislelizumab and anlotinib, resulting in a significant shrinkage of the lung tumor. Subsequently, anlotinib was discontinued due to bleeding in the brain metastasis, and the patient received two additional cycles of tislelizumab. Following improvement in the hemorrhage from brain metastasis, the patient received two cycles of treatment with tislelizumab and anlotinib. Treatment was subsequently interrupted for 1 month due to the coronavirus disease 2019 (COVID-19) pandemic, which then resumed with two additional cycles of tislelizumab and anlotinib. Finally, the patient refused to continue treatment due to the progression of the brain metastasis and economic conditions, despite the stable condition. At this point, the patient has achieved over a year of progression-free survival, with overall survival exceeding 39 months. This case illustrates the efficacy and safety of combining antitumor immunotherapy with anlotinib, a targeted anti-angiogenic therapy.

BackgroundThe 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).MethodsIn 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.ResultsThe 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.ConclusionsThe 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.Clinical Trial Registrationhttps://www.chictr.org.cn/, identifier ChiCTR2100043772.

Abstract Background Chronic nonspecific cheilitis is a complex condition characterized by persistent lip peeling and discomfort. This case report explores the clinical progression of a patient with history of tongue squamous cell carcinoma and subsequent Tislelizumab treatment, presenting with persistent lip peeling. Case presentation A patient with a history of tongue squamous cell carcinoma (T2N0M0), treated with chemotherapy, surgery, and Tislelizumab, presented with six months of persistent lip peeling. Clinical examination revealed distinct features of chronic nonspecific cheilitis with infectious angular cheilitis (Oral Candidiasis). A tailored treatment plan, emphasizing oral hygiene practices and local treatments with Sodium Bicarbonate, Tacrolimus ointment, and Chlortetracycline ointment. Follow-up visits demonstrated sustained improvement, highlighting the significance of individualized approaches. Conclusions This case underscores the importance of recognizing and managing oral manifestations in patients with a history of cancer and immunotherapy. The patient’s response to treatment suggests that a multifaceted approach, combining local therapy with lifestyle modifications, can be effective in managing chronic nonspecific cheilitis associated with immunotherapy. Routine follow-up appointments, guided by personalized medicine principles, contribute to sustained patient well-being.

Background: Chronic nonspecific cheilitis is a complex condition characterized by persistent lip peeling and discomfort. This case report explores the clinical progression of a patient with history of tongue squamous cell carcinoma and subsequent Tislelizumab treatment, presenting with persistent lip peeling. Case presentation: A patient with a history of tongue squamous cell carcinoma (T2N0M0), treated with chemotherapy, surgery, and Tislelizumab, presented with six months of persistent lip peeling. Clinical examination revealed distinct features of chronic nonspecific cheilitis with infectious angular cheilitis (Oral Candidiasis). A tailored treatment plan, emphasizing oral hygiene practices and local treatments with Sodium Bicarbonate, Tacrolimus ointment, and Chlortetracycline ointment. Follow-up visits demonstrated sustained improvement, highlighting the significance of individualized approaches. Conclusions: This case underscores the importance of recognizing and managing oral manifestations in patients with a history of cancer and immunotherapy. The patient's response to treatment suggests that a multifaceted approach, combining local therapy with lifestyle modifications, can be effective in managing chronic nonspecific cheilitis associated with immunotherapy. Routine follow-up appointments, guided by personalized medicine principles, contribute to sustained patient well-being. [ABSTRACT FROM AUTHOR]

Objective response rate (ORR) was also better with TACE-Len-T treatment (ORR: 72.1% vs 29.4%, P< 0.001), and the disease control rate (DCR) significantly increased in the TACE-Len-T group (88.2% vs 48.5%, P< 0.001). Multivariate analyses revealed that TACE-Len treatment, tumor number > 3, and cTACE were independent risk factors for OS, whereas TACE-Len treatment was the only independent risk factor for PFS. The frequency and severity of AEs in the TACE-Len-T group were comparable to those in the TACE-Len group (any grade: 92.6% vs 91.2%, P=0.753; grade 3 or 4: 33.8% vs 32.3%, P=0.855). Conclusion: TACE-Len-T treatment significantly improved OS, PFS, ORR, and DCR over TACE-Len treatment, with a manageable safety profile in uHCC. [ABSTRACT FROM AUTHOR]

Sinonasal squamous cell carcinoma (SNSCC) is the most common, highaggressive sinonasal malignancies that have remained relatively stable poor outcomes over the past decade. As a first-line treatment for SNSCC, surgery plus adjuvant radiotherapy is recommended. However, complete surgical resection may not be appropriate due to the proximity of the nasal cavity and sinuses to key structures such as orbit or intracranial. Currently, immune checkpoint inhibitors (ICIs) have been established as one of the first-line therapies for many solid tumors with unresectable stage. However, evidence on the efficacy of ICIs in sinonasal malignancy is scarce and no ICIs are approved for use in SNSCC up to day. In this report, we report a case of a 64-year-old man with SNSCC treated by multi-protocol exploration. The patient achieved pathological complete response (pCR) after receiving two cycles of Docetaxel and cisplatin combined with tislelizumab. To the best of our knowledge, this is the first case of SNSCC treated with tislelizumab that achieved pCR. This case offers real-world evidence that chemotherapy plus immunotherapy is a promising treatment for SNSCC. [ABSTRACT FROM AUTHOR]

Periampullary carcinoma is a malignant gastrointestinal tumor originating from the head of the pancreas, distal bile duct, duodenum, or the ampulla of Vater. Currently, surgery remains the primary treatment option, yet the postoperative recurrence rate remains high. Chemotherapy is the main approach for controlling postoperative recurrence. Histologically, periampullary carcinoma is categorized into two types: intestinal (IN) and pancreaticobiliary (PB) subtype. Each subtype requires different therapeutic approaches, with the PB type primarily treated with gemcitabine and the IN type with 5-FU. Despite these options, patient outcomes are still unsatisfactory. In recent years, the feasibility of immunotherapy in tumor treatment has been increasingly evidenced, although research on its efficacy in periampullary carcinoma treatment is still limited. In this report, we present a case of a periampullary carcinoma patient who experienced recurrence and metastasis after undergoing radical pancreatoduodenectomy and receiving gemcitabine-based chemotherapy post-surgery. Through next-generation sequencing (NGS), we identified high expression levels of programmed cell death-ligand 1 (PD-L1) with a combined positive score (CPS) of 35, high tumor mutation burden (TMB-H), and high microsatellite instability (MSI-H) in this patient. Therefore, we implemented a combination therapy using Tislelizumab and chemotherapy. According to the latest follow-up, the tumors are effectively controlled. Our utilization of immunotherapy combined with chemotherapy holds significant implication for the treatment of periampullary carcinoma. [ABSTRACT FROM AUTHOR]

This work was designed to assess the cost-effectiveness of front-line tislelizumab plus chemotherapy (TIS+Chemo) in advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC) with positive expression of programmed cell death ligand 1 (PD-L1) from the perspective of Chinese healthcare system. A 10-year partitioned survival model was undertaken utilizing clinical data from RATIONALE 305. Costs and utilities were both discounted at an annual rate of 5%. The primary outcome was incremental cost-effectiveness ratios (ICERs) and calculated as the cost per quality-adjusted life years (QALYs). The willingness-to-pay (WTP) threshold was set as $18,625/QALY. Only direct medical costs were considered. Sensitivity analyses and subgroup analyses were performed to evaluate the robustness of the model. In the base-case analysis, the incremental cost and effectiveness associated with TIS+Chemo vs Chemo was 7,361 and 0.38 QALYs, respectively, leading to an ICER of 19,371/QALY. At the WTP threshold of $18,625/QALY, the TIS+Chemo was not a cost-effective first-line treatment option. The model outcomes were robust. TIS+Chemo did not provide a cost-effective approach for PD-L1 positive advanced GC/GEJC in China setting. However, TIS+Chemo might be cost-effective in provinces with higher WTP threshold. RATIONALE 305, , identifier is NCT03777657. [ABSTRACT FROM AUTHOR]

Background: The efficacy of immunotherapy plus neoadjuvant chemotherapy and concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC) has not been reported. This study retrospectively compared the efficacy of tislelizumab plus neoadjuvant chemotherapy and CCRT with neoadjuvant chemotherapy followed by CCRT. Methods: Ninety patients with stages III–IVa NPC were identified between January 2020 and March 2021 at the Affiliate Hospital of Guangdong Medical University. Forty-three patients in the observation group (OG) received tislelizumab plus nano albumin–paclitaxel and cisplatin (nab-TP) regimen, followed by CCRT, while forty-seven patients in the control group (CG) received nab-TP regimen followed by CCRT. Results: The complete response rate after neoadjuvant therapy was significantly higher in the OG compared to the CG (37.2% vs. 12.8 %). The objective response rates were 88.4 % in the OG and 70.2 % in the CG. The 3-year progression-free survival (PFS) rates for OG and CG patients were 93.0 % and 78.7 %, respectively (P = 0.04, HR = 0.31). The overall survival (OS) rates for the OG and the CG were 95.3 % and 87.2 %, respectively (P = 0.15, HR = 0.36). Locoregional relapse-free survival (LRFS) rates were 90.7 % for the OG and 72.3 % for the CG (P = 0.04, HR = 0.38), and distant metastasis-free survival (DMFS) rates were 95.3 % for the OG, and 80.9 % for the CG (P = 0.04, HR = 0.30). For PD-L1 high-expression and low-expression rates, the 3-year PFS rates were 89.2 % and 85.7 % (P = 0.77, HR = 1.21), and the OS rates were 90.2 % and 89.2 % (P = 0.65, HR = 1.36), respectively. Conclusion: Tislelizumab combined with neoadjuvant chemotherapy and CCRT showed encouraging therapeutic effects and good tolerability in patients with LA-NPC compared to the standard treatment.

Extramammary Paget disease (EMPD) is a rare epithelial adenocarcinoma in apocrine-gland rich skin, involving the vulva, the scrotum, and the penis. with distant metastases and a poor prognosis. Local EMPD patients generally have a good prognosis, with expected 5-year survival of 60%–92%, but distant metastasis represents poor prognosis and 5-year survival of 10%. Treatment approaches for advanced EMPD are chemotherapy and biological agents, which carry limited efficacy. We report the case of a 57-year-old man diagnosed with metastatic EMPD, who showed a long-term disease control with a combination therapy (an immune checkpoint inhibitor - tislelizumab plus chemotherapy – paclitaxel albumin and cisplatin). This patient underwent a wide penile scrotal lesion excision and six cycles of tislelizumab plus chemotherapy. The patient achieved partial response for the metastatic lesions according to the Response Evaluation Criteria in Solid Tumors (version 1.1). This case report supports further investigation of the combination treatment of chemotherapy and immune checkpoint inhibitors in the management of metastatic EMPD, which currently has an abysmal prognosis and no standardized treatment.

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) represents a particularly aggressive subtype of gastric carcinoma characterized by elevated rates of vascular invasion, lymphatic dissemination, hepatic metastasis, and an unfavorable clinical outcome. Treatment strategies for AFPGC have historically lacked specificity. Herein, a case is presented involving AFPGC in which the patient exhibited a notable response to combined anti-PD-1 antibody immunotherapy and SOX chemotherapy, potentially achieving a cure. This report marks the first application of this regimen in neoadjuvant therapy for AFP gastric cancer, followed by radical resection and postoperative adjuvant therapy.Case summaryA 62-year-old male patient presented with persistent upper abdominal distension and discomfort lasting over 2 months. Initial investigations revealed markedly elevated serum alpha-fetoprotein (AFP) levels, and subsequent pathological examination confirmed the diagnosis of AFPGC via gastroscopy. Due to the patient’s condition, surgical resection was initially deemed unfeasible. Therefore, a chemo-immunotherapy regimen consisting of SOX chemotherapy and the PD-1 inhibitor tislelizumab was administered for 3 cycles. Following this, successful laparoscopic radical gastrectomy was performed. The treatment protocol was continued with an additional 3 cycles postoperatively. At the time of this case report, the patient maintained a good quality of life with no evidence of disease recurrence or adverse events.ConclusionThe present report highlights a case of AFPGC where significant therapeutic success was achieved through a combined regimen of chemotherapy and immunotherapy, both before and after surgery. The use of anti-PD-1 antibody (tislelizumab) in combination with SOX regimen (S-1 and oxaliplatin) demonstrated effective treatment of AFPGC, potentially offering a curative approach. This approach represents a promising targeted therapy option for patients with AFPGC.

Background Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the beneft of its combination with immunotherapy needs to be verifed. This study evaluated the efcacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. Methods In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight≥60 kg: 12 mg;<60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon’s two-stage design,>6 responders were needed in stage 1 (n=30) to continue the study, and≥18 responders were needed by the end of stage 2 (n=60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. Results Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p=0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the frst 60 patients of the efcacy evaluable analysis set (n=62). After a median follow-up of 15.7 months, confrmed ORR and disease control rate were 38.7% (24/62, 95% confdence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade≥3 treatment-related adverse events occurred in 18 (28.1%) patients. Conclusions Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as frst-line therapy for patients with uHCC. [ABSTRACT FROM AUTHOR]

Tislelizumab may induce immune-related adverse events, especially adverse skin events. Early detection and timely intervention of cutaneous adverse events are crucial to improve patients' quality of life and reduce the disruption of therapeutic regimens. This study aimed to determine the clinical characteristics of cutaneous adverse reactions to tislelizumab and offer a reference for its rational clinical use. Case reports of cutaneous adverse reactions induced by tislelizumab were collected from the relevant databases (up to 31 March 2023). Patient age, sex, primary disease, medication use, occurrence of adverse skin conditions, treatment, and outcomes were recorded and descriptively analysed. A total of 13 patients were enrolled, including six males and seven females, aged 55–79 years, with a median age of 75 years and a mean age of 70.92 ± 8.84 years. The original disease was lung carcinoma in none patients, cervical carcinoma in two, and urothelial carcinoma and squamous cell carcinoma in one each. The time from the initiation of medication use to the occurrence of cutaneous adverse reactions ranged from 7 to 177 days. Among the 13 patients, 10 showed improvement after drug withdrawal or symptomatic treatment. Two patients died (one died of disease progression and multiorgan failure, one died of acute coronary syndrome), and one patient's adverse skin reactions persisted without treatment. Tislelizumab-related cutaneous adverse reactions mostly occur after several days to months of treatment. In clinical practice, evaluation and monitoring should be strengthened. More attention should be paid to erythema and rashes, which may be signs of serious adverse skin reactions. Early detection and intervention can ensure the safe use of drugs and provide greater clinical benefits to patients. [ABSTRACT FROM AUTHOR]

Abstract Background The promising therapeutic outcomes of neoadjuvant immunotherapy combined with chemotherapy in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by several phase II clinical trials and have been widely demonstrated in clinical work. Theoretically, postoperative adjuvant immunotherapy may further improve the therapeutic effect, but there is still lack of evidence. The aim of this study was to analyse the safety and efficacy of perioperative immunotherapy (tislelizumab) in locally advanced resectable thoracic ESCC (PILOT trial). Methods Seventy-three eligible patients with pathologically confirmed thoracic ESCC of clinical T1b-3N1-3M0 or T3N0M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab 200 mg d1, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel 260 mg/m2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with pathologic complete response (pCR) after esophagectomy received adjuvant tislelizumab (200 mg every 3 weeks for up to one year), and patients with non-pCR were assigned adjuvant tislelizumab plus chemotherapy for two cycles and then maintenance tislelizumab (200 mg every 3 weeks for up to 15 cycles). The primary endpoint of this study is 2-year disease-free survival (DFS) in non-pCR patients. The secondary endpoints include pCR rate, major pathological response rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival. Discussion This protocol was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital (IS23059). This is the first prospective clinical trial to investigate the safety and efficacy of perioperative immunotherapy for locally advanced resectable thoracic ESCC. We hypothesize that perioperative immunotherapy could be a promising therapeutic strategy that can provide better 2-year DFS in non-pCR patients. Trial registration ClinicalTrial.gov: NCT0605633.

The survival rate and quality of life of patients with advanced gastric cancer are low. Despite the continuous development and improvement of chemotherapy regimens for advanced gastric cancer, the survival rate of patients with advanced gastric cancer is still low. At present, not only are comprehensive treatment methods very limited for advanced gastric cancer, but there is also a lack of posterior treatment methods. Therefore, there is an urgent need for effective treatment plans for advanced gastric cancer. In recent years, with the in-depth research on tumor immunology, immunotherapy has become a focus of attention. Programmed cell death protein-1 (PD-1) inhibitor, as an immunosuppressive drug, combined with chemotherapy, can not only maximize the clinical activity of immunosuppressive drug, but also establish a lasting immune response. At present, the combination of PD-1 inhibitors and platinum chemotherapy has shown high clinical application value in clinical research of advanced gastric cancer. This article reviews the research progress of PD-1 inhibitors combined with chemotherapy for advanced gastric cancer, aiming to provide a basis for clinical application.

In recent years, with the in-depth study of PD-1/PD-L1 related pathways, great progress has been made in cancer immunotherapy. However, the immunotherapy regimen for mccRCC is still controversial in clinical practice.A 50-year-old man with mccRCC complicated with renal venous tumor thrombus from 2019 to present, including surgical treatment, targeted therapy and the combined treatment regimen of “Tislelizumab combined with Sunitinib”. Although he experienced a roller coaster of adverse reactions during treatment, the patient's prognosis was good.Tislelizumab combined with Sunitinib is safe and effective in the Treatment of mccRCC.

Objectives: The efficacy of treatments targeting recurrent or metastatic head and neck squamous cell carcinoma are unsatisfactory in practice for patients with a ECOG PS score ≥ 2. Thus, this study retrospectively evaluated the safety and efficacy of a programmed cell death 1 inhibitor (tislelizumab) combined with an epidermal growth factor receptor inhibitor (nimotuzumab) in treating patients with a PS score ≥ 2 who suffer from recurrent or metastatic oral squamous cell carcinoma (OSCC). Materials and methods: Fifteen patients were treated with tislelizumab (200 mg IV Q3W) and nimotuzumab (200 mg IV Q3W). Programmed cell death-ligand 1 (PD-L1) expression in tumor biopsies was assessed with immunohistochemistry. Whole-exome sequencing was used to evaluate treatment efficacy based on PDL1 expression and gene mutation. Results: At a median follow-up of 9.6 months, median overall survival was 10.1 months, and median progression-free survival was 4.0 months. Overall response rate was 40%, with 6/15 patients achieving partial response. Eight patients exhibited nine adverse events, eight out of nine being grade 2 and the remaining being grade 3. Whole-exome sequencing showed that DYNC1I2, THSD7A, and FAT1 mutations were associated with patient prognosis. Conclusion: Combination therapy involving tislelizumab plus nimotuzumab is a promising, low-toxicity treatment for recurrent or metastatic OSCC in patients with a PS score ≥ 2. [ABSTRACT FROM AUTHOR]

Background: The promising therapeutic outcomes of neoadjuvant immunotherapy combined with chemotherapy in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by several phase II clinical trials and have been widely demonstrated in clinical work. Theoretically, postoperative adjuvant immunotherapy may further improve the therapeutic effect, but there is still lack of evidence. The aim of this study was to analyse the safety and efficacy of perioperative immunotherapy (tislelizumab) in locally advanced resectable thoracic ESCC (PILOT trial). Methods: Seventy-three eligible patients with pathologically confirmed thoracic ESCC of clinical T1b-3N1-3M0 or T3N0M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab 200 mg d1, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel 260 mg/m2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with pathologic complete response (pCR) after esophagectomy received adjuvant tislelizumab (200 mg every 3 weeks for up to one year), and patients with non-pCR were assigned adjuvant tislelizumab plus chemotherapy for two cycles and then maintenance tislelizumab (200 mg every 3 weeks for up to 15 cycles). The primary endpoint of this study is 2-year disease-free survival (DFS) in non-pCR patients. The secondary endpoints include pCR rate, major pathological response rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival. Discussion: This protocol was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital (IS23059). This is the first prospective clinical trial to investigate the safety and efficacy of perioperative immunotherapy for locally advanced resectable thoracic ESCC. We hypothesize that perioperative immunotherapy could be a promising therapeutic strategy that can provide better 2-year DFS in non-pCR patients. Trial registration: ClinicalTrial.gov: NCT0605633. [ABSTRACT FROM AUTHOR]

We aimed to describe the clinical efficacy and safety of tislelizumab, a new (PD-1) inhibitor, in patients with malignant solid tumors. We searched relevant databases for phase III randomized controlled trials, including patients with solid tumors. The following outcomes are of interest: overall response rate (OS), overall survival (ORR), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events (TRAE). We conducted subgroup analyses based on the line of therapy, type of solid tumor, and tislelizumab alone or combined with chemotherapy. Seven phase III RCTs with 3478 were included in the meta-analysis. Pooled analysis demonstrated that tislelizumab significantly improved ORR and DCR with (OR) of 2.59 (95% (CI) = 2.15–3.12, p < 0.00001) and 1.78 (95% CI = 1.43–2.21, p > 0.00001), respectively. Pooled HRs for OS and PFS were 0.71 (95% CI = 0.65-0.78, p > 0.00001) and 0.68 (95% CI = 0.54–0.84, p = 0.0005), respectively. Overall, based on this meta-analysis, the available data strongly supports the utilization of tislelizumab in the treatment of malignant solid tumors. CRD42023408815 [ABSTRACT FROM AUTHOR]

Objectives: Recently updated results of randomized clinical trials (RCTs) have confirmed that toripalimab, camrelizumab, and tislelizumab plus chemotherapy (TOGP, CAGP, and TIGP) significantly prolonged survival compared to placebo plus chemotherapy (PLGP) in the first‐line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M‐NPC). However, the high cost of immunotherapies imposes a huge financial burden on patients and health care systems. Materials and methods: RCTs estimating immunotherapies for R/M‐NPC were searched. A Bayesian network meta‐analysis (NMA) was carried out; the main outcomes were hazard ratios (HRs) of overall survival (OS) and progression‐free survival (PFS). The cost and efficacy of four first‐line therapies were evaluated using the Markov model. The main outcome in the cost‐effectiveness analysis (CEA) was incremental cost‐utility ratios (ICURs). The model robustness was assessed by one‐way, three‐way, and probabilistic sensitivity analyses. Results: Three RCTs (JUPITER‐02, CAPTAIN‐1st, and RATIONALE‐309) involving 815 patients were included in the NMA. Compared with PLGP, chemo‐immunotherapies have significantly longer PFS and OS. Compared to the PLGP group, TOGP, CAGP, and TIGP groups resulted in additional costs of $48 339, $22 900, and $23 162, with additional 1.89, 0.73, and 0.960 QALYs, respectively, leading to the ICURs of $25 576/QALY, $31 370/QALY, and $31 729/QALY. Pairwise comparisons showed TOGP was the most cost‐effective option among chemo‐immunotherapy groups. Conclusion: From the Chinese payers' perspective, first‐line immunotherapy combination therapies provided significant survival and cost‐effectiveness superiority over chemotherapy alone for patients with R/M‐NPC at the WTP of $38 029/QALY. Among the three chemo‐immunotherapy groups, TOGP was the most cost‐effective option. [ABSTRACT FROM AUTHOR]

Abstract Background The failure rate after neoadjuvant chemoradiotherapy followed by surgery is approximately 34.6%–48% for resectable esophageal carcinoma. Pathologic complete response after neoadjuvant chemoradiotherapy is an important factor in predicting lower recurrence and better survival. Whether the sequential addition of immunotherapy to neoadjuvant chemoradiotherapy will be beneficial to improving the pathologic complete response rate is unknown. Methods Patients with pathologically confirmed thoracic esophageal squamous cell carcinoma and at clinical T1-2N1-3M0 or T3-4aN0-3M0 (stage II–IVA) according to the eighth edition of American Joint Committee on Cancer staging will be allocated to receive neoadjuvant radiotherapy (41.4 Gy with 23 fractions to planning target volume) with concurrent chemotherapy (albumin-bound paclitaxel, 100 mg/m2, once weekly for five weeks; carboplatin, area under the curve of 2 mg/mL/min, once weekly for five weeks) plus tislelizumab monotherapy sequentially (200 mg every three weeks for three cycles, beginning from the first to the 14th day after the end of radiotherapy). Then, subtotal esophagectomy with two-field lymphadenectomy, including the whole mediastinum and abdomen, will be performed. The primary endpoint for this study is the pathologic complete response rate after neoadjuvant chemoradiotherapy plus tislelizumab. Discussion The optimal timing of the combination of immunotherapy and neoadjuvant chemoradiotherapy in esophageal carcinoma is not determined. The results of this phase II trial will be helpful to clarify the safety and efficacy of the sequential addition of tislelizumab after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal carcinoma. Trial registration This study was approved on January 26, 2021 and retrospectively registered with ClinicalTrials.gov ( NCT04776590 ) on March 1, 2021.

Abstract Background Activated immune cells (IC) in the tumor microenvironment (TME) are critical for anti-tumor efficacy. Greater understanding of the dynamic diversity and crosstalk between IC is needed to clarify their association with immune checkpoint inhibitor efficacy. Methods Patients from three tislelizumab monotherapy trials in solid tumors (NCT02407990, NCT04068519, NCT04004221) were retrospectively divided into subgroups by CD8+ T-cell and macrophage (Mφ) levels, assessed via multiplex immunohistochemistry (mIHC; n = 67) or gene expression profiling (GEP; n = 629). Results A trend of longer survival was observed in patients with both high CD8+ T-cell and Mφ levels versus other subgroups in the mIHC analysis (P = 0.11), which was confirmed with greater statistical significance in the GEP analysis (P = 0.0001). Co-existence of CD8+ T cells and Mφ was coupled with elevated CD8+ T-cell cytotoxicity, T-cell trafficking, MHC class I antigen presentation signatures/genes, and enrichment of the pro-inflammatory Mφ polarization pathway. Additionally, a high level of pro-inflammatory CD64+ Mφ density was associated with an immune-activated TME and survival benefit with tislelizumab (15.2 vs. 5.9 months for low density; P = 0.042). Spatial proximity analysis revealed that closer proximity between CD8+ T cells and CD64+ Mφ was associated with a survival benefit with tislelizumab (15.2 vs. 5.3 months for low proximity; P = 0.024). Conclusions These findings support the potential role of crosstalk between pro-inflammatory Mφ and cytotoxic T cells in the clinical benefit of tislelizumab. Trial registration NCT02407990, NCT04068519, NCT04004221.

Abstract Bladder cancer is a common malignant tumor of the genitourinary system, with the primary cause of death being metastasis. The most common metastatic sites are the lymph nodes, liver, lung, bone, peritoneum, pleura, kidney, adrenal gland, and the intestine. Brain and heart metastases are rare. In this report, we describe a patient who had pulmonary lymph node metastases more than a year after being diagnosed with bladder cancer, followed by brain and cardiac metastases more than two years later. Following the failure of standard first-line chemotherapy, the patient accepted 6 cycles of tislelizumab immunotherapy. The re-examination revealed that the bilateral frontal brain metastases had vanished, the right temporal lobe metastases had been greatly decreased, the neurological symptoms had been alleviated, and the cardiac metastases had disappeared. This is a rare clinical case with encouraging effects of tislelizumab and can serve as a model for the treatment of similar patients.

Purpose: Pembrolizumab and tislelizumab have demonstrated significant clinical benefits in first-line treatment for advanced NSCLC. However, no head-to-head clinical trial has ever compared the optimal choice. Therefore, we conducted an indirect comparison to explore the optimal choice for advanced NSCLC combined with chemotherapy. Methods: We conducted a systematic review of randomized trials; the clinical outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Indirect comparisons between tislelizumab and pembrolizumab were conducted with the Bucher method. Results: Data were abstracted from 6 randomized trials involving more than 2,000 participants. Direct meta-analysis showed that both treatment regimens improved clinical outcomes compared with chemotherapy alone (PFS: hazard ratio (HR)tis+chemo/chemo 0.55, 95% CI 0.45-0.67; HRpem+chemo/chemo 0.53, 95% CI 0.47-0.60; ORR: relative risk (RR)tis+chemo/chemo 1.50, 95% CI 1.32-1.71; RRpem+chemo/chemo 1.89, 95% CI 1.44-2.48). Regarding safety outcomes, tislelizumab and pembrolizumab have a higher risk in the incidence of grade 3 or higher AEs (RRtis+chemo/chemo 1.12, 95% CI 1.03-1.21; RRpem+chemo/chemo 1.13, 95% CI 1.03-1.24). The indirect comparison showed that there was no significant difference between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy in terms of PFS (HR: 1.04, 95% CI 0.82-1.31), ORR (RR: 0.79, 95% CI 0.59-1.07), the incidence of grade 3 or higher AEs (RR 0.99, 95% CI 0.87-1.12), and AEs leading to death (RR 0.70, 95% CI 0.23-2.09). In progressionfree survival subgroup analysis, the results demonstrate no significant differences in PFS by PD-L1 TPS expression level, age, liver metastasis status, and smoking status between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy. Conclusion: The efficacy and safety of tislelizumab combination chemotherapy were not substantially different from pembrolizumab combination chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid cancer (ATC) is a rare but highly fatal form of thyroid cancer. This highly malignant tumor progresses rapidly and is prone to relapse and metastasis, with a poor prognosis. Novel treatments have improved survival in recent years, but the outcome of treatment is not satisfactory. Case presentation: We report a case of multiple postoperative recurrences of papillary thyroid carcinoma that later transformed into undifferentiated carcinoma. The patient’s neck mass was huge and the operation was unsuitable. Then, she achieved remarkable tumor shrinkage by tislelizumab immunotherapy combined with radiotherapy. Conclusion: This case indicates that radiotherapy combined with immunotherapy is a promising treatment for ATC. Such a combined approach warrants further study. [ABSTRACT FROM AUTHOR]

Objectives: Immunotherapy plus chemotherapy has recently been applied in the neoadjuvant treatment for locally advanced gastric cancer (LAGC), while its superiority over neoadjuvant chemotherapy (NACT) alone remains to be explored. This study explored the safety and efficacy of NACT plus tislelizumab in patients with LAGC. Methods: The data on patients with LAGC who received NACT combined with radical gastrectomy and NACT plus tislelizumab followed by radical gastrectomy was retrospectively collected. Clinicopathological characteristics of the two groups were compared. Results: A total of 119 and 50 patients with gastric cancer treated with NACT and NACT plus tislelizumab, respectively, were enrolled. No significant difference was found between the baseline data of the two groups. The operative time (210.5 ± 70.4 min vs. 237.6 ± 68.4 min, P=0.732), intraoperative blood loss (157.8 ± 75.9 ml vs. 149.1 ± 92.5 ml, P=0.609), and number of dissected lymph nodes (24.7 ± 9.3 vs. 28.1 ± 10.3, P=0.195) was not statistically different between the two groups. In comparison to the NACT plus tislelizumab group, the R0 resection rate (100% vs. 89.9%, P=0.019) and pathologic complete response rate (26.0% vs. 3.4%, P<0.001) were significantly lower in the NACT group. The postoperative complication rates were 24.4% and 26.0% in the NACT and NACT plus tislelizumab groups with no significant difference (P=0.823). In subgroup analysis, tumor regression grade (TRG) (TRG 3: 72.3% vs. 23.5%, P<0.001) and ypN stage (stages 2-3: 46.8% vs. 5.9%, P=0.003) in the NACT group were significantly higher compared with the NACT plus tislelizumab group in esophagogastric junction carcinoma. Conclusion: Compared with the S-1 and oxaliplatin (SOX) or 5-fluorouracil, folinic acid, and oxaliplatin (FOLFOX) NACT regimen, NACT plus tislelizumab significantly improved the efficacy and R0 resection rate of LAGC without increasing the incidence of perioperative complications, particularly in esophagogastric junction carcinoma. [ABSTRACT FROM AUTHOR]

Background: Abdominal lymph node (ALN) metastasis is associated with a poor prognosis in patients with hepatocellular carcinoma (HCC) because of the limited number of effective therapeutic options available. Immunotherapy with immune checkpoint inhibitors, such as those targeting programmed death receptor-1 (PD-1), have produced encouraging results in patients with advanced HCC. Here, we report a complete response (CR) in a patient with advanced HCC and ALN metastasis after combination treatment with tislelizumab (a PD-1 inhibitor) and locoregional therapy. Case summary: A 58-year-old man with HCC experienced progressive disease with multiple ALN metastases after undergoing transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), and laparoscopic resection. Because the patient did not wish to receive systemic therapy, including chemotherapy and targeting therapy, we prescribed tislelizumab (as a single immunotherapeutic agent) together with RFA. After four tislelizumab treatment cycles, the patient achieved a CR without tumor recurrence for up to 15 months. Conclusion: Tislelizumab monotherapy can be effectively used to treat advanced HCC with ALN metastasis. Moreover, the combination of locoregional therapy and tislelizumab is likely to further increase therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) is a rare and aggressive soft tissue tumor with a high degree of malignancy and rapid progression, usually occurring in the extremities, retroperitoneum, and abdomen, whereas it rarely arises in the mediastinum, and is treated mainly by surgical resection. The prognosis of patients with advanced sarcoma is poor, and doxorubicin monotherapy is the standard first-line chemotherapy for most advanced soft tissue sarcomas (STS), but the prognosis is generally unsatisfactory. Immune checkpoint inhibitors (ICIs) have been established as therapies for many solid cancers in recent years; however, evidence on the efficacy of ICIs in undifferentiated sarcoma is scarce, mostly consisting of small studies, and no ICIs are currently approved for use in sarcomas. We report a case of a middle-aged man with primary mediastinal UPS with high PD-L1 expression (TPS was approximately 80%) and TLS positive. The patient was treated with sequential tislelizumab monotherapy maintenance after 6 cycles of tislelizumab combined with epirubicin, efficacy evaluation was partial remission (PR), progression-free survival (PFS) was 8.5 months, and grade 1 fatigue was identified as an adverse event. [ABSTRACT FROM AUTHOR]

Background: The failure rate after neoadjuvant chemoradiotherapy followed by surgery is approximately 34.6%–48% for resectable esophageal carcinoma. Pathologic complete response after neoadjuvant chemoradiotherapy is an important factor in predicting lower recurrence and better survival. Whether the sequential addition of immunotherapy to neoadjuvant chemoradiotherapy will be beneficial to improving the pathologic complete response rate is unknown. Methods: Patients with pathologically confirmed thoracic esophageal squamous cell carcinoma and at clinical T1-2N1-3M0 or T3-4aN0-3M0 (stage II–IVA) according to the eighth edition of American Joint Committee on Cancer staging will be allocated to receive neoadjuvant radiotherapy (41.4 Gy with 23 fractions to planning target volume) with concurrent chemotherapy (albumin-bound paclitaxel, 100 mg/m2, once weekly for five weeks; carboplatin, area under the curve of 2 mg/mL/min, once weekly for five weeks) plus tislelizumab monotherapy sequentially (200 mg every three weeks for three cycles, beginning from the first to the 14th day after the end of radiotherapy). Then, subtotal esophagectomy with two-field lymphadenectomy, including the whole mediastinum and abdomen, will be performed. The primary endpoint for this study is the pathologic complete response rate after neoadjuvant chemoradiotherapy plus tislelizumab. Discussion: The optimal timing of the combination of immunotherapy and neoadjuvant chemoradiotherapy in esophageal carcinoma is not determined. The results of this phase II trial will be helpful to clarify the safety and efficacy of the sequential addition of tislelizumab after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal carcinoma. Trial registration: This study was approved on January 26, 2021 and retrospectively registered with ClinicalTrials.gov (NCT04776590) on March 1, 2021. [ABSTRACT FROM AUTHOR]

Background: Activated immune cells (IC) in the tumor microenvironment (TME) are critical for anti-tumor efficacy. Greater understanding of the dynamic diversity and crosstalk between IC is needed to clarify their association with immune checkpoint inhibitor efficacy. Methods: Patients from three tislelizumab monotherapy trials in solid tumors (NCT02407990, NCT04068519, NCT04004221) were retrospectively divided into subgroups by CD8+ T-cell and macrophage (Mφ) levels, assessed via multiplex immunohistochemistry (mIHC; n = 67) or gene expression profiling (GEP; n = 629). Results: A trend of longer survival was observed in patients with both high CD8+ T-cell and Mφ levels versus other subgroups in the mIHC analysis (P = 0.11), which was confirmed with greater statistical significance in the GEP analysis (P = 0.0001). Co-existence of CD8+ T cells and Mφ was coupled with elevated CD8+ T-cell cytotoxicity, T-cell trafficking, MHC class I antigen presentation signatures/genes, and enrichment of the pro-inflammatory Mφ polarization pathway. Additionally, a high level of pro-inflammatory CD64+ Mφ density was associated with an immune-activated TME and survival benefit with tislelizumab (15.2 vs. 5.9 months for low density; P = 0.042). Spatial proximity analysis revealed that closer proximity between CD8+ T cells and CD64+ Mφ was associated with a survival benefit with tislelizumab (15.2 vs. 5.3 months for low proximity; P = 0.024). Conclusions: These findings support the potential role of crosstalk between pro-inflammatory Mφ and cytotoxic T cells in the clinical benefit of tislelizumab. Trial registration: NCT02407990, NCT04068519, NCT04004221. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of tislelizumab combined with PC regimen (pemetrexed + cisplatin) in the treatment of advanced lung cancer. METHODS: Totally 82 patients with advanced lung cancer in the hospital from Feb. 2021 to Feb. 2022 were extracted to be divided into the observation group (n =41) and the control group (n = 41) via the random number table method. The control group was treated with PC regimen, while the observation group received tislelizumab on the basis of the control group. The disease remission rate and adverse reactions were compared between two groups. Before treatment, after 2 cycles of treatment and after 4 cycles of treatment, the levels of serum carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and cytokeratin 19 fragment (CYFRA21-1), T lymphocytes, serum phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt) were compared between two groups. RESULTS: The disease remission rate of 56. 10% (23/41) in the observation group was higher than that of 34. 15% (14/41) in the control group, with statistically significant difference (P < 0. 05). After 2 cycles of treatment and after 4 cycles of treatment, the serum levels of CEA, CA125, CYFRA21-1, PI3K and Akt in two groups were lower than those before treatment, and after 4 cycles of treatment were lower than after 2 cycles of treatment, and the observation group were lower than the control group, with statistically significant differences (P<0. 05). After 2 cycles of treatment and after 4 cycles of treatment, the levels of CD3+, CD4+, CD4+ / CD8+ in the observation group were higher than those before treatment and higher than those in the control group, with statistically significant differences (P<0. 05). There was no significant difference in the incidence of adverse reactions between two groups (P >0. 05). CONCLUSIONS: The efficacy of tislelizumab combined with PC regimen in the treatment of advanced lung cancer is significant, which can reduce the level of tumor markers, inhibit the PI3K/ Akt signaling pathway and enhance immune function with higher safety. [ABSTRACT FROM AUTHOR]

Background: Gallbladder cancer (GBC) is a rare malignant tumour of the bile duct. Due to the lack of typical clinical manifestations in the early stage, it is basically at an advanced stage when discovered. Radical resection remains the only curative therapy for patients with GBC. The resection rate is relatively low due to tumour invasion and metastasis, and the overall prognosis is poor. For most patients with unresectable lesions, chemotherapy has been the only recommended treatment for decades. Immunotherapy combined with TKIs (tyrosine kinase inhibitors) was proven to be effective in patients with hepatocellular carcinoma and cholangiocarcinoma. Some physicians have attempted to apply immunotherapy and TKIs combined with traditional chemotherapy in patients with advanced GBC. However, the outcomes were not clear because limited cases were reported. Case presentation: We present a case series of four elderly patients with advanced GBC who received tislelizumab and lenvatinib combined with chemotherapy. All four patients responded to this treatment approach. Tumour responses were better in Patient 1 (TMB-H, MSS), Patient 2 (low TMB, MSS), and Patient 3 (low TMB, MSI-H) than in Patient 4 (low TMB, MSS), in whom metastasis occurred during the later stage of treatment. Conclusion: The combination of tislelizumab and lenvatinib may be a promising treatment for patients with advanced GBC. The efficacy and safety need further confirmation. [ABSTRACT FROM AUTHOR]

In recent years, immunotherapy has made breakthroughs in the field of malignant tumors, and more and more novel immune checkpoint inhibitors have been developed, revolutionizing the first-line, second-line and post-line treatment options for malignant tumors. Tislelizumab is a domestically developed inhibitor of programmed death-1 (PD-1). The drug has shown good antitumor potential and safety in classical Hodgkin's lymphoma, uroepithelial carcinoma, non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma and gastric cancer/gastroesophageal junction carcinoma. In this review, the structure and mechanism of action, pharmacodynamics and pharmacokinetics, clinical research and adverse reactions of tislelizumab are reviewed to provide reference for clinical application.

Immunotherapy plus chemotherapy has been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC, stage IV). Recently, the 2023 version of the National Comprehensive Cancer Network Guidelines recommended immunotherapy plus chemotherapy as the neoadjuvant regimen in patients with resectable non-small cell lung cancer (NSCLC). However, it is still unclear whether the combination regimen of immunotherapy plus chemotherapy is also beneficial for SCLC in the neoadjuvant context.Here, we report the case of a patientwith stage IIIB SCLC who showed long-term survival and good tolerance to the neoadjuvant chemoimmunotherapy consisting of tislelizumab (an anti--PD-1 monoclonal antibody) plus etoposide-carboplatin. The patient achieved pathological complete response after receiving two cycles of neoadjuvant tislelizumab and chemotherapy followed by surgery. Two courses of postoperative tislelizumab and etoposide-carboplatin treatment were performed. The patient has survived for more than 23 months with no recurrence or metastases after neoadjuvant therapy. Multiplexed immunofluorescence and immunohistochemistry staining showed that the post-treatment specimens had remarkable immune cells infiltration, including CD3+ T cells, CD4+ T cells, and CD8+ T cells, which contrasted with very low levels of these cells in the pretreatment samples. This study is, to the best of our knowledge, the first attempt to present the neoadjuvant chemoimmunotherapy of tislelizumab in combination with etoposide-carboplatin in SCLC. Our study suggested that neoadjuvant tislelizumab plus chemotherapy may facilitate radical resection and benefit patients with locally advanced (stage IIB-IIIC) SCLC. [ABSTRACT FROM AUTHOR]

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9–18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8–20]; two or more prior lines, 13% [95% CI, 7–20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC. [ABSTRACT FROM AUTHOR]

Bladder cancer is a common malignant tumor of the genitourinary system, with the primary cause of death being metastasis. The most common metastatic sites are the lymph nodes, liver, lung, bone, peritoneum, pleura, kidney, adrenal gland, and the intestine. Brain and heart metastases are rare. In this report, we describe a patient who had pulmonary lymph node metastases more than a year after being diagnosed with bladder cancer, followed by brain and cardiac metastases more than two years later. Following the failure of standard first-line chemotherapy, the patient accepted 6 cycles of tislelizumab immunotherapy. The re-examination revealed that the bilateral frontal brain metastases had vanished, the right temporal lobe metastases had been greatly decreased, the neurological symptoms had been alleviated, and the cardiac metastases had disappeared. This is a rare clinical case with encouraging effects of tislelizumab and can serve as a model for the treatment of similar patients. [ABSTRACT FROM AUTHOR]

Abstract Pulmonary sarcomatoid carcinoma (PSC), characterized by poor differentiation, aggressive progression, and early metastasis, is a rare type of non‐small cell lung carcinoma (NSCLC), which shows a low response rate to conventional antitumor therapies and has a poor prognosis. With the achievements in gene sequencing, targeted therapy, and immunotherapy, several new approaches have recently been explored in PSC treatment. A small case series of PSC patients were found to have programmed death‐ligand 1 (PD‐L1) overexpression, a prerequisite for PD‐1 inhibiting therapy, which made immunotherapy possible. However, anti‐PD‐1 treatment for PSCs was still at a preliminary stage. Here, we report the successful outcome of tislelizumab monotherapy in a patient with advanced PSC with pleural invasion, thus providing a novel promising approach for PSC patients with PD‐L1 overexpression.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is an extremely rare and poor-prognosis malignancy, which has recently been noted as a subtype of lung tumors. We presented a case of SMARCA4-UT in a 50-year-old man with progressively worsening respiratory failure. The tumor was the first reported to involve pulmonary artery, and 90% of tumor cells expressed programmed cell death ligand 1 (PD-L1). High tumor mutational burden (TMB, 23.93/Mb) and mutations in SMARCA4 were detected. It is the first reported case to receive Tislelizumab monotherapy with considerable improvement in clinical condition and no adverse events. As a result of our case, we highlight the importance of recognizing SMARCA4-UT as an individual entity, as well as the efficacy of immune checkpoint inhibitor therapy, particularly in patients with high levels of TMB and PD-L1 expression.

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive disease without standardized treatment strategies. The efficacy of second-line or beyond immune checkpoint inhibitors (ICIs) has been proven in recent studies, whereas the evidence for first-line immunotherapy for PSC is still limited to case reports and remains poorly understood.Materials and methodsThis was a multicenter, retrospective analysis of 21 patients with a histological diagnosis of PSC who received ICI as first-line therapy from January 2019 to March 2022. The expression of PD-L1 was evaluated by immunohistochemistry (IHC) using the monoclonal antibody 22C3. Low and high PD-L1 expressions were defined using the tumor proportion score (TPS), with cutoffs of 1 and 50%, respectively.ResultsAll eight patients had PD-L1 positivity who underwent PD-L1 expression assessment, and six patients (6/8, 75.0%) had high PD-L1 expression. Among the 21 PSC patients, seven received tislelizumab, six received camrelizumab, four received sintilimab, three received pembrolizumab, and one received durvalumab. Among them, 18 PSCs received combination therapy, whereas another three PSCs received immunotherapy alone. Out of the 21 PSC patients, 12 (57.1%) achieved a partial response (PR), and five patients had stable disease (SD) as the best response, whereas four PSCs experienced dramatic progressive disease (PD). The median progression-free survival (PFS) was 9.2 (95% CI [4.3, 14.1]) months, and the median OS was 22.8 (95% CI [4.0, 41.5]) months. Among the three treatment groups (immunotherapy alone, immunotherapy combined with anlotinib, and chemoimmunotherapy), the median PFS was 8.0, 9.4, and 9.6 months, and the median OS was 19.0, 22.8, and 30.6 months, respectively. There was no difference in PFS and OS between the three treatment regimen groups (P = 0.86 and P = 0.34, respectively) and different immunotherapies (P = 0.10 and P = 0.23, respectively). No serious adverse events (grade ≥ 3) were noted.ConclusionFirst-line immunotherapy has promising therapeutic potential in the treatment of PSC. More studies are warranted to confirm these findings.