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Abstract Background Immune checkpoint inhibitor (ICI) therapy has been widely investigated in urothelial carcinoma; however, the utility of ICI therapy in the treatment of organ transplant recipients with metastatic urothelial carcinoma (mUC) is unclear. We herein report the first case of a first-line anti-programmed cell death-1 (anti-PD-1) monotherapy for a kidney transplant patient with mUC. Case presentation A 71-year-old woman who received a kidney transplant in 2003 was diagnosed with urothelial carcinoma in 2018. After operation of the tumor, the patient developed local recurrence at the site of the right kidney and bladder and multiple distant metastases in May 2020. Considering the intolerance of chemotherapy and high tumor mutation burden, we administered the anti-PD-1 agent tislelizumab (200 mg every three weeks). Partial response was achieved after two cycles of therapy and sustained until 18th cycles. There were no signs of kidney graft rejection. The immunotherapy was temporarily stopped after the 18th course because of a suspicious immune-related pneumonitis and was continued in December 2021. Conclusions This case demonstrates the feasibility of safely achieving stable cancer control in a kidney transplant patient with mUC without encountering graft rejection by using single-agent anti-PD-1 treatment.

Abstract Background Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. Methods This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. Discussion In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. Trial registration This study was registered at www.clinicaltrials.gov . Trial registration number: NCT05972655. Date of registration: 31 July 2023.

Abstract Objectives This retrospective study evaluated the individual benefits of tislelizumab and surgery, as well as their synergistic effect on progression-free survival (PFS) and overall survival (OS) of stage II-III non-small cell lung cancer (NSCLC) patients. Methods From September 2019 to June 2022, all participants with potentially resectable NSCLC who received chemotherapy (C) or tislelizumab plus chemotherapy (T) were included in the study. Participants were categorized into four groups based on surgery or not (S or NS) and the utilization of tislelizumab (T or C). Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan–Meier method and log-rank test, as well as Cox proportional hazards models. Results Compared to C, T was associated with significantly higher objective response rate (64.54% vs. 34.78%, p = 0.003), higher pathological complete response rate (40.00% vs. 14.06%, p = 0.007), and higher major pathological response rate (60.00% vs. 20.31%, p

Jiayun Jiang,1 Hui Zhang,1 Jiejuan Lai,1 Shiyu Zhang,1 Yanjiao Ou,1 Yu Fu,2,&ast; Leida Zhang1,&ast; 1Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leida Zhang, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email 2518569931@qq.com Yu Fu, Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, Beibei District, Chongqing, 400715, People’s Republic of China, Email fuyu2020@swu.edu.cnPurpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib and tislelizumab (TACE-Len-T) versus TACE plus lenvatinib (TACE-Len) as the first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).Patients and Methods: This retrospective study included 136 uHCC patients treated with TACE-Len-T or TACE-Len from January 1, 2021, to June 30, 2023. Clinical outcomes including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared between the two groups. The risk factors affecting OS and PFS were also analyzed.Results: The median OS and PFS of the TACE-Len-T group were significantly longer than those of the TACE-Len group (Median OS: not reached vs 13.8 months, P< 0.001; Median PFS: 13.0 months vs 2.7 months, P< 0.001). The best overall 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.Keywords: unresectable hepatocellular carcinoma, transarterial chemoembolization, lenvatinib, tislelizumab, immunotherapy

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.

Abstract The RATIONALE-306 study revealed that patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC) could benefit from treatment with tislelizumab plus chemotherapy. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy for treating OSCC from the perspective of the Chinese healthcare system. Partitioned survival model estimated the cost-effectiveness of tislelizumab plus chemotherapy compared with chemotherapy alone for treating OSCC using RATIONALE-306 data. Costs and utilities were obtained from local databases and published studies. Costs, quality-adjusted life-years (QALYs), life-years, incremental cost-effectiveness ratios (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were outcomes. Price simulation were conducted at the willingness-to-pay (WTP) threshold. Sensitivity and subgroup analyses were performed to assess model robustness. Compared with chemotherapy alone, tislelizumab plus chemotherapy yielded an ICER of USD 27,896/QALY, gained an additional 0.414 QALYs and 0.751 life-years, and increased the cost by USD 11,560. Probabilistic sensitivity analysis revealed that tislelizumab plus chemotherapy was cost-effective at the WTP of USD 38,258/QALY with probability of 94.43%. When the price in China was less than USD 3.714 per mg, the price simulation results indicated that tislelizumab plus chemotherapy was cost-effective at a WTP threshold of USD 38,258. Tislelizumab plus chemotherapy yielded an INHB of 0.112 QALYs and an INMB of USD 4,279 compared with chemotherapy alone at a WTP threshold of USD 38,258. Based on the sensitivity analyses, the above results were stable. A general trend was observed for subgroups with better survival benefits related to a higher probability of cost-effectiveness. From the Chinese healthcare perspective, tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as a first-line therapy for OSCC. These findings can help clinicians make optimal clinical decisions and assist decision-makers in evaluating the cost-effectiveness of tislelizumab in clinical practice.

Abstract Background Despite adequate transurethral resection of the bladder tumor (TURBT) followed by intravesical bacillus-calmette guérin (BCG), high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is associated with high rates of recurrence and progression. Immune checkpoint inhibitors can improve antitumor activity in bladder cancer, but relevant evidence in HR-NMIBC is limited. Thus, we evaluated the efficacy and safety of the tislelizumab-based combination regimen in HR-NMIBC. Methods A retrospective study included 21 patients diagnosed with HR-NMIBC between July 2020 and September 2022. All patients underwent TURBT followed by combination regimens of tislelizumab plus BCG with or without gemcitabine/cisplatin (GC) chemotherapy. Clinical Data on demographics and characteristics, treatment information, outcomes, and safety were collected and analyzed. Results Among the 21 patients with HR-NMIBC, the median age was 63 years (range 39–85), with the majority of patients with stage T1 (16/21, 76.19%). The median treatment of tislelizumab was 5 cycles (range 1–12) and the median number of BCG instillations was 12 times (range 2–19). Of the 21 patients, 15 (71.43%) received combination chemotherapy with GC, with a median treatment of 2 cycles (range 0–7); others did not. Overall, after the median follow-up of 25 months (range 7–31), the estimated 2-year bladder recurrence-free survival rate was 78.64% (95% confidence intervals [CIs], 50.79–91.83%), 2-year cystectomy-free survival rate was 83.00% (95% CI 53.53–94.59%), and 2-year disease-free survival rate was 73.39% (95% CI 46.14–88.36%). Sixteen stage T1 patients achieved a distant metastasis-free survival rate of 95.45% (95% CI 71.87–99.34%) at 2 years. Fourteen (66.67%) patients experienced at least one treatment related-AEs (TRAEs), with 9.52% (2/21) of grade 3–4. Grade ≥ 3 TRAEs were hypophysitis (1/21, 4.76%) and myasthenia (1/21, 4.76%). No treatment-related deaths were observed. Conclusions The study demonstrated promising clinical benefits and a manageable safety profile of tislelizumab-based combination regimen as a bladder-sparing treatment of HR-NMIBC.

Abstract Background The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC. Methods Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed. Results Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon‐gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group. Conclusions A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored. Trial registration ClinicalTrials.gov, NCT05024266. Registered August 27, 2021.

Xianmin Zhu,1 Shuang Dong,1 Jing Tang,1 Rong Xie,1 Huijing Wu,1 Jun Guan,2 Sheng Hu1 1Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hematology, Wuhan NO.1 Hospital, Wuhan, People’s Republic of ChinaCorrespondence: Sheng Hu, Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 116 South Road, Wuhan, 430079, People’s Republic of China, Email ehusmn@163.comAbstract: In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death − 1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient’s enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.Keywords: hepatocellular carcinoma, complete response, immune checkpoint inhibitor, tislelizumab, chemotherapy failure, metastasis

PurposeThe efficacy of tislelizumab plus chemotherapy in improving progression-free survival (PFS) and overall survival (OS) in unresectable gastric or gastroesophageal junction cancer (GC/GEJC) has recently been emphasized. This study compared the cost-effectiveness of tislelizumab plus chemotherapy versus placebo plus chemotherapy for the United States (US) and Chinese populations.MethodsUsing data from the RATIONALE-305 phase 3 trial, a Markov model was developed to analyze quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net health benefits (INHBs), and incremental net monetary benefits (INMBs). The health state utilities and direct medical costs were obtained from the relevant literature and local cost databases. The model uncertainty was evaluated using sensitivity analyses.FindingsIn the base-case analysis, the addition of tislelizumab to chemotherapy yielded an ICER of $37,768.48 per QALY in China, slightly below the willingness-to-pay (WTP) threshold of $38,042.49 per QALY, showing marginal cost-effectiveness with an INHB of 0.05 QALYs and an INMB of $1,852.49. Subgroup analyses revealed ICERs of $23,853.52 for patients with a PD-L1 TAP score ≥ 5% (TAP ≥ 5%). In the US, the ICER was $502,786.22 per QALY in the intent-to-treat (ITT) and $321,395.28 per QALY in the TAP ≥ 5% subgroup, exceeding the US WTP threshold of $150,000.00.ImplicationsIn China, tislelizumab plus chemotherapy is a cost-effective first-line therapy for unresectable GC/GEJC in both ITT and TAP ≥ 5% subgroups. In the US, tislelizumab plus chemotherapy is not cost-effective.

Abstrcat: Basal cell carcinoma (BCC) of the prostate is a rare and enigmatic tumor with uncertain biological behavior and treatment modalities. Some studies suggest that BCC exhibits invasive characteristics and a high degree of malignancy, necessitating proactive management and vigilant monitoring. Notably, there is a lack of reported effective treatment utilizing programmed cell death protein-1 (PD-1) inhibitors for advanced BCC of the prostate. This study explores the efficacy of tislelizumab, as a single-agent therapy, in the successful treatment of advanced prostate BCC.

IntroductionGemcitabine and cisplatin remain the cornerstone for the treatment of advanced or unresectable biliary tract cancers, but the incidence rate of the grade 3 or 4 toxic effects is high (70.7%). In recent years, significant progress has been achieved in the systemic treatment of cholangiocarcinoma with immune checkpoint inhibitors (ICIs), targeted therapy, and hepatic artery infusion chemotherapy (HAIC). HAIC may elevate the local drug concentration in the liver to 10–100 times the drug plasma concentration; therefore, it may enhance tumor cytotoxicity while minimizing systemic adverse effects. HAIC combined with immunotherapy and targeted therapy resulted in acceptable tumor responses and tolerable toxic effects in the treatment of hepatocellular carcinoma (HCC). However, whether this combination strategy can benefit patients with unresectable intrahepatic cholangiocarcinoma remains unclear.Methods and AnalysisWe describe a single-arm, open label, prospective clinical trial of HAIC sequential transcatheter arterial embolization (TAE) combined with tislelizumab and surufatinib in patients with unresectable intrahepatic cholangiocarcinoma. TAE + HAIC was performed at an interval of at least 3 weeks, and oxaliplatin (85 mg/m2) and rituximab (3 mg/m2) were infused. TAE was performed using undrugged microspheres. Tislelizumab was infused every 3 weeks and surufatinib was administered orally once a day, with 3-5 capsules (50 mg/capsule) each time. We plan to enroll 28 participants in this study. The primary study endpoint was objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), conversion to surgical resection rate, overall survival (OS), 1-year OS rate, disease control rate (DCR), quality of life (QoL), and incidence of adverse events.Trial registration numberNCT06239532.

BackgroundRecently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer.MethodsThis is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution.DiscussionThis is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma.Clinical trial registrationClinicalTrials.Gov, identifier NCT06266871.

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.

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.

ObjectiveComparing the efficacy of transarterial chemoembolization (TACE) combined with lenvatinib plus tislelizumab (TLT) with TACE combined with lenvatinib (TL) for unresectable hepatocellular carcinoma, particularly in determining which patients can benefit more from the TLT treatment.MethodsFrom March 2021 to September 2023, a total of 169 patients from three centers were included in this study, with 103 patients receiving TLT and 66 patients receiving TL. The Kaplan-Meier method was utilized to evaluate the cumulative overall survival (OS) and progression-free survival (PFS) between the two groups and were assessed using the log-rank test. Subgroup analysis on tumor number, maximum tumor diameter, presence of portal vein thrombosis, AFP level, and Child-Pugh class were conducted.ResultsThe median OS was 26 months in the TLT group, and 20 months in the TL group. The median PFS was 14 months in the TLT group and 9 months in the TL group. The Kaplan-Meier curve demonstrated a significantly superior OS and PFS in the TLT group compared to the TL group. Subgroup analysis showed that for patients with a maximum tumor diameter greater than 7 cm, AFP > 400 ng/ml and accompanied by portal vein tumor thrombus, and Child-Pugh class A, there was a statistically significant difference in OS between TLT and TL groups.ConclusionsOS and PFS were significantly improved in patients who received TLT compared to those who received TL, patients with a largest tumor diameter greater than 7 cm, AFP > 400 ng/ml, Child-Pugh class A and PVTT appeared to derive more benefit.

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.

Pulmonary sarcomatoid carcinoma (PSC), a rare non-small cell lung cancer (NSCLC) subtype, poses diagnostic and treatment difficulties. Current research explores targeted therapies and immunotherapy to improve patient outcomes. This case report details a male patient diagnosed with PSC via pathology. Tests revealed high levels of PD-L1, a marker suggesting potential benefit from immune checkpoint inhibitors. However, despite bronchoscopic intervention, his advanced stage IIIB cancer (cT3N2bM0) progressed quickly, with progression-free survival (PFS) under 3 months. Following progression, the patient received tislelizumab (anti-PD-1 antibody) and anlotinib (an anti-angiogenic drug) as second-line therapy. This combination showed promise, achieving near-partial remission after the first cycle. Subsequent scans documented continued tumor shrinkage until the patient experienced fatal hemoptysis. This case highlights the potential benefits of combining tislelizumab with anlotinib for PSC. However, it also represents the first reported case of fatal hemoptysis with this specific treatment regimen. This finding emphasizes the need for increased awareness of this potential complication, especially in patients with centrally located PSC treated with anti-angiogenic agents like anlotinib.

BackgroundOlder patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment.Case presentationWe report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm × 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months.ConclusionThe case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes.

BackgroundThe efficacy of a regimen combining Tegafur, Gimeracil and Oteracil Potassium Capsules (S-1), oxaliplatin (SOX) with trastuzumab and tislelizumab chemotherapy for advanced gastric cancer (GC) has not been reported.Case summaryA 56-year-old male was diagnosed with GC combined with peripheral lymph node metastasis. The patient received neoadjuvant chemotherapy, including SOX, tislelizumab and trastuzumab. After 4 cycles of chemotherapy, the tumor shrank significantly, and radical surgery was performed with good clinical results. To date, the patient has been followed up for 6 months with no significant side effects.ConclusionIn this study, the patient received combination chemotherapy with SOX trastuzumab and tislelizumab and successfully underwent radical surgery with good clinical outcomes. Combined SOX with trastuzumab and tislelizumab may be an effective neoadjuvant chemotherapy regimen.

Abstract Background Esophageal carcinoma is a type of cancer that occurs in the esophagus. For patients with locally advanced or metastatic esophageal squamous cell carcinoma who have either experienced disease progression following first-line standard chemotherapy or are intolerant to it, the prognosis is typically poor. Additionally, these patients often bear a substantial economic burden during the course of their treatment. Tislelizumab is a selective PD-1 inhibitor with efficacy proven in locally advanced or metastatic esophageal squamous cell carcinoma. The study aims to evaluate the cost-effectiveness of tislelizumab versus camrelizumab as the second-line treatment in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients in China. Methods From the perspective of China’s healthcare system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime horizon. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from RATIONALE 302 trial and the published ESCORT study due to the lack of head-to-head clinical trials. Only direct medical costs were included. Costs and utility values were derived from local charges, the published literature, and related databases. Sensitivity analyses and a scenario analysis were also performed to verify the robustness of the model results. Results Compared with camrelizumab monotherapy, tislelizumab monotherapy incurred a lower lifetime cost ($8,346 vs. $8,851) and yielded higher quality-adjusted life-years (QALYs) (0.87 vs. 0.63), which resulted in an incremental cost-effectiveness ratio (ICER) of -$2,051/QALY. Tislelizumab monotherapy is a dominant option over camrelizumab monotherapy in China. The three primary parameters upon which this result was most sensitive were the unit cost of camrelizumab, the unit cost of tislelizumab, and the duration of reactive cutaneous capillary endothelial proliferation (RCCEP). According to the probabilistic sensitivity analysis (PSA), tislelizumab monotherapy was 100% cost-effective when the WTP was 1–3 times GDP per capita in China($11,207/QALY∼$33,621/QALY). Scenario analysis showed that the result was consistent. Conclusion Tislelizumab monotherapy is a dominant option compared with camrelizumab monotherapy as the second-line treatment for locally advanced or metastatic ESCC in China.

Abstract Background Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. Methods A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. Conclusions and relevance Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.

A 66-year-old female patient presenting with dysphagia was diagnosed with stage IV unresectable gastric cancer (cTxN+M1). Multiple liver metastases were identified. The patient subsequently underwent five courses of chemotherapy and immunotherapy, including the capecitabine plus oxaliplatin (XELOX) regimen combined with tislelizumab. After fifth course treatment, it was confirmed that the liver metastases had completely disappeared and the primary tumor had significantly reduced in size. Consequently, a laparoscopy was performed, revealing a retraction-like response in the primary tumor and no obvious metastases in the abdominal cavity. Subsequently, a radical total gastrectomy was carried out through open abdominal surgery. Pathological analysis showed no remaining cancer or lymph node metastases, and the tumor regression was classified as grade 0. The patient has been now receiving additional chemotherapy and immunotherapy to manage any potential residual metastases. This case illustrated the rare and significant impact of combining chemotherapy with tislelizumab, transitioning the treatment approach from palliative to curative. It highlighted the critical role of immunotherapy in managing advanced gastric cancer with liver metastases.

The combination therapy of Tislelizumab plus Lenvatinib has recently emerged as the new standard of care for unresectable hepatocellular carcinoma (HCC). This treatment has demonstrated a significant reduction in tumor burden, raising the possibility of conversion therapy. However, the full safety and efficacy of this combination in real-world settings are not yet fully understood. We recently reported the case of a 36-year-old man with initially unresectable massive HCC, for whom radical surgery (RS) was contraindicated. After receiving Tislelizumab/Lenvatinib plus transarterial chemoembolization (TACE), the patient achieved complete pathological remission and subsequently underwent RS. The patient did not experience postoperative severe complications, and there was no recurrence during the follow-up period. Tislelizumab/Lenvatinib plus TACE therapy may lead to a complete pathological response in advanced HCC. Nevertheless, the safety of prolonged treatment needs to be assessed.

Background and aimThe prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy.MethodsFrom February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.ResultsThe follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%).ConclusionHAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

BackgroundTislelizumab is the first PD-1 inhibitor in China to demonstrate superior efficacy in second-line or third-line treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of tislelizumab compared to docetaxel from a Chinese healthcare system perspective.MethodsA dynamic Markov model was developed to evaluate the cost-effectiveness of tislelizumab in comparison to docetaxel in second or third-line treatment. The efficacy data utilized in the model were derived from the RATIONALE-303 clinical trial, while cost and utility values were obtained from the drug data service platform and published studies. The primary outcomes of the model encompassed quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to validate the robustness of the base case analysis results.ResultsThe tislelizumab group demonstrated a cost increase of CNY 117,473 and a gain of 0.58 QALYs compared to the docetaxel group, resulting in an ICER value of CNY 202,927 per QALY gained.ConclusionThe administration of tislelizumab in patients with advanced or metastatic NSCLC not only extends the progression-free survival (PFS) and overall survival (OS). Moreover, this treatment demonstrates a favorable cost-effectiveness profile across the Chinese population.

BackgroundCoinfection with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) occurs in 5–67% of patients with HIV. HIV weakens the human immune system and leads to various tumors. Patients with unresectable hepatocellular carcinoma (HCC) and HIV experience poor treatment efficacy and have a short survival period. Approximately 70% of cases of HCC are diagnosed at advanced stages due to the subtle onset of the disease. As a result, most cases are not suits for curative therapy. Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC and is commonly used to treat unresectable HCC in China. Recent advancements in systemic treatments have significantly enhanced the effectiveness of unresectable HCC treatment. Several previous study showed that combination treatment combination therapy can enhance the efficacy. Notably, studies proposed that TACE combined targeted drugs with immune checkpoint inhibitors results in a high objective response rate and overall survival. However, the novelty of this study lies in its report of a complete response using a triple combination in patients with HIV and HCC with main trunk portal vein tumor thrombus.Case presentationA 57-year-old woman was diagnosed with HCC with a main trunk portal vein tumor thrombus combined with HIV infection, cirrhosis, and chronic viral hepatitis. She underwent TACE and was administered donafenib and tislelizumab. This triple therapy treatment regimen resulted in a clinical complete response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on contrast-enhanced computed tomography.ConclusionWe first used TACE combined with donafenib and tislelizumab for HCC patients with main trunk portal vein tumor thrombus and HIV-HBV coinfection and achieved complete response.

Sinonasal squamous cell carcinoma (SNSCC) is the most common, high-aggressive 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.

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.

Breast cancer remains one of the predominant malignancies worldwide. In the context of inoperable advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, systemic management primarily relies on HER2-targeting monoclonal antibodies. With the successful development of anti-HER2 antibody-drug conjugates (ADCs), these agents have been increasingly integrated into therapeutic regimens for metastatic breast cancer. Here, we present the case of a 42-year-old female patient with HER2-positive pulmonary metastatic breast cancer who underwent an extensive treatment protocol. This protocol included chemotherapy, radiation therapy, hormonal therapy, surgical intervention on the breast, and anti-HER2 therapies. The anti-HER2 therapies involved both singular and dual targeting strategies using trastuzumab and the ADC disitamab vedotin (RC48) over an 8-year period. After experiencing disease progression following HER2-targeted therapy with RC48, the patient achieved noticeable partial remission through a therapeutic regimen that combined trastuzumab deruxtecan (DS8201) and tislelizumab. The data suggest a promising role for DS8201 in managing advanced stages of HER2-amplified metastatic breast cancer, especially in cases that demonstrate progression after initial HER2-directed therapies using ADCs. Furthermore, its combination with anti-PD-1 agents enhances therapeutic efficacy by augmenting the anti-tumoral immune response.

Abstract Background In the management of urothelial carcinoma, patient selection for immunotherapy, particularly with immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1), is important for treatment efficacy. Inflammatory markers are useful for predicting treatment outcomes and immune-related adverse events (irAEs). This study aims to retrospectively explore the associations between inflammatory markers and outcomes in patients with postoperative urothelial carcinoma undergoing tislelizumab (PD-1 inhibitor) adjuvant therapy. Methods A retrospective analysis was conducted on 133 patients with postoperative urothelial carcinoma who received tislelizumab adjuvant therapy at the Affiliated Hospital of Xuzhou Medical University from April 2020 to August 2023. The prognostic effects of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) on disease-free survival (DFS) and overall survival (OS) were assessed using Cox regression models. The correlation between inflammatory markers and the onset of irAEs was analyzed using logistic regression models. Results NLR 5 and MLR >0.31, respectively. Multivariate analysis revealed that an NLR 135. Patients who experienced irAEs had longer DFS and OS. Multivariate analysis demonstrated that irAEs were an independent prognostic risk factor for DFS and OS. There was no significant difference in the occurrence of irAEs among different NLR, PLR, and MLR groups. Conclusion In patients with postoperative urothelial carcinoma receiving tislelizumab adjuvant therapy, the assessment of NLR and MLR before treatment may serve as valuable predictive markers of clinical outcome.

Abstract Background A combination of immune checkpoint inhibitors (ICIs) and chemotherapy has demonstrated excellent clinical efficacy and safety in treating a variety of cancers, including urothelial carcinoma (UC). However, its efficacy and safety in patients with muscle-invasive upper tract urothelial carcinoma (UTUC) who are undergoing radical surgery remain uncertain. The purpose of this retrospective study was to examine the effectiveness and safety of tislelizumab combined with gemcitabine plus cisplatin (TGC) as a first-line postoperative adjuvant treatment in this population. Methods This single-center, real-world study retrospectively analyzed the data from 71 patients with muscle-invasive UTUC who had radical nephroureterectomy (RNU) at the Affiliated Hospital of Xuzhou Medical University between November 1, 2020, and November 1, 2023. Among the 71 patients, 30 received adjuvant therapy of TGC within 90 days after RNU and 41 underwent surveillance. No patients receive preoperative neoadjuvant therapy. The TGC therapy group received adjuvant therapy every 3 weeks postoperatively until the first recurrence, first metastasis, or death due to any reason, whichever occurred first. The patients were followed up telephonically and through outpatient visits to record and evaluate their disease-free survival (DFS) and treatment-related adverse events (TRAEs). Results This study assessed the DFS of 41 and 30 patients in the surveillance group and TGC therapy group, respectively. The median DFS of the surveillance group was 16.5 [95% confidence interval (CI), 14.7–18.3] months, while the median DFS of the TGC group has not yet reached [hazard ratio (HR) 0.367 (95% CI, 0.169–0.796); p = 0.008], with 21 patients still undergoing follow-up. Compared with the surveillance group, the TGC therapy group had dramatically improved DFS after RNU and reduced risk by 63.3%. Of the 30 patients receiving combination therapy, 28 experienced TRAEs; all TRAEs were consistent with the frequently reported events in the chemotherapy-alone regimens, and there were no treatment-related deaths. Conclusion This study demonstrates that TGC therapy exhibits excellent clinical efficacy in patients undergoing radical surgery, significantly improving DFS and displaying great safety.

Objective: To explore the efficacy of tislelizumab combined with pemetrexed and carboplatin chemotherapy in elderly patients with advanced lung adenocarcinoma and its effects on serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels. Methods: Ninety-four driver gene-negative elderly patients with advanced lung adenocarcinoma admitted to the Fourth Affiliated Hospital of Nanjing Medical University from July 2021 to December 2022 were selected as the study subjects. They were divided into chemotherapy group (pemetrexed combined with carboplatin, n=48) and tislelizumab group (pemetrexed+carboplatin+tislelizumab, n=46) by the random number table method, and both groups were treated for 4 cycles, with 21 days as a cycle. The clinical efficacy, immune function ［T lymphocyte subsets (CD4+, CD8+, CD4+/CD8+］ and serum indicators (IGF-1, IGFBP-3) before and after treatment were recorded in both groups, and the adverse reactions were assessed. Results: The clinical efficacy and objective response rate (58.70% vs 29.17%, χ2=8.329, P＜0.01) in tislelizumab group were significantly higher than those in chemotherapy group. After 4 cycles of treatment, the CD4+, CD4+/CD8+ and IGFBP-3 levels in both groups were significantly increased compared with those before treatment (P＜0.05), and the indicators in tislelizumab group were higher than those in chemotherapy group (P＜0.05); CD8+ and IGF-1 levels were significantly decreased in both groups compared with those before treatment (P＜0.05), and the indicators in tislelizumab group were lower than those in chemotherapy group (P＜0.05). Adverse reactions were mainly grade 1-2 in both groups, and there was no significant difference in the incidence of adverse reactions between two groups (P＞0.05). Conclusion: The first-line therapy of tislelizumab combined with platinum-containing dual-drug for elderly advanced lung adenocarcinoma can improve the clinical efficacy, improve the balance of CD4+/CD8+, regulate the expression of serum IGF-1 and IGFBP-3 levels. The adverse reactions are controllable, and the treatment regimen is safe and reliable.

Abstract Purpose Whether the addition of tislelizumab to gemcitabine and cisplatin (GC) chemotherapy increases the incidence of myelosuppression has not been well established. This study identified the risk factors for the development of myelosuppression in patients with urothelial carcinoma (UC) after receiving GC chemotherapy with or without tislelizumab. Materials and Methods We enrolled 192 UC patients who received GC with or without tislelizumab at the Affiliated Hospital of Xuzhou Medical University between July 2014 and November 2022. Patient baseline characteristics were included in the statistical analyses after adjusting for previously reported risk factors affecting survival using propensity score matching (1:1). Binary logistic regression analysis was used to identify the risk factors associated with posttreatment myelosuppression. Results A total of 192 patients were enrolled, of whom 96 were treated with tislelizumab plus gemcitabine and cisplatin (T + GC) and 96 with GC alone. The incidence of leukopenia, anemia, and thrombocytopenia of any grade was 50.0%, 70.8%, and 42.7%, respectively, in the T + GC group and 41.7%, 72.9%, and 20.8%, respectively, in the GC group. In multivariate analysis, patients aged over 70 years (OR = 2.486, 95% CI: 1.067–5.792, p = 0.035) and those who received T + GC (OR = 3.119, 95% CI: 1.576–6.173, p = 0.001) were more likely to develop thrombocytopenia. Patients aged over 70 years (OR = 3.213, 95% CI: 1.254–8.237, p = 0.015) were more likely to develop anemia, and patients with renal insufficiency (OR = 2.105, 95% CI: 1.035–4.280, p = 0.040) were more likely to develop leukopenia. Eventually, 99 (51.6%) patients with UC successfully completed all the treatment cycles. Conclusions This study demonstrates that the addition of tislelizumab to GC chemotherapy led to a considerable increase in the occurrence of thrombocytopenia, whereas no significant changes were observed regarding anemia or leukopenia. It is crucial to fully inform patients at increased risk for myelosuppression of potential risks and closely monitor changes in their blood routines.

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.

Abstract Background Tislelizumab is an anti-programmed death-1 (PD-1) monoclonal antibody with a construction that enables it to have a higher affinity to its target. We aimed to evaluate tislelizumab’s safety and efficacy for treating non-small cell lung cancer (NSCLC). Methods Embase, Scopus, PubMed, Web of Science, and Google Scholar were searched up to December 20, 2022. The review only included randomized controlled trials (RCTs) that evaluated the safety or efficacy of tislelizumab for treating patients with lung cancer. The revised Cochrane risk-of-bias tool (RoB2) was utilized to evaluate study quality. Results There were four RCTs identified, which included 1565 patients with confirmed locally advanced or metastatic squamous and/or non-squamous types of NSCLC. Treatment with tislelizumab was associated with better progression-free survival (PFS) and objective response rate (ORR), particularly when used in combination with chemotherapy. Almost all patients in both arms reported at least one treatment-emergent adverse event (TEAE). Decreased hematologic indexes accounted for more than 20% of the grade ≥ 3 TEAEs in the tislelizumab plus chemotherapy group. The proportion of TEAE that led to death in the tislelizumab plus chemotherapy arms ranged from 3.2 to 4.2%. Hypothyroidism, pneumonitis, and hyperglycemia were the most frequently noted immune-mediated adverse events in the tislelizumab group. Conclusions Tislelizumab, whether used alone or in combination with chemotherapy, seems to demonstrate both a safety and efficacy as a treatment for NSCLC.

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT.

IntroductionFirst-line treatment with tislelizumab plus chemotherapy has shown clinical benefits for patients with advanced or metastatic esophageal squamous cell carcinoma (OSCC) in China, while its economic burden is unknown. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy from the perspective of the Chinese healthcare system.MethodsWe constructed a partitioned survival model to compare the cost-effectiveness of tislelizumab plus chemotherapy with chemotherapy in patients with advanced OSCC. Patient characteristics and clinical outcomes were extracted from RATIONALE-306. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were selected as the study outcomes. Sensitivity analysis and subgroup analysis were conducted to test the stability of the results.ResultsTislelizumab plus chemotherapy provided additional 0.48 QALYs with the incremental cost of $16,587.2 than chemotherapy, of which ICER was $34,699.72 per QALY. When the willingness-to-pay threshold was set as $37,260, the novel therapy had a probability of 77% to be cost-effective. Our base-case analysis results were sensitive to utilities of progression-free survival and progression of disease. Our subgroup analysis showed that the novel therapy was associated with cost-effectiveness in patients with a high expression of PD-L1.ConclusionTislelizumab plus chemotherapy was likely to be more cost-effective compared with chemotherapy in the first-line therapy of advanced OSCC from the perspective of the Chinese healthcare system. Our findings can provide clinicians and decision-makers with evidence of the cost-effectiveness of tislelizumab.

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.

Metastatic triple-negative breast cancer (mTNBC) has the worst prognosis among breast cancer subtypes. Immune checkpoint inhibitors (ICIs) plus chemotherapy have promising survival benefits. Herein, we report a 51-year-old woman whose metastatic lesions were diagnosed as triple-negative subtype and who received tislelizumab plus eribulin treatment and achieved excellent efficacy. To our knowledge, this study is the first attempt to present tislelizumab in combination with eribulin for mTNBC treatment. New treatments resulting in prolonged survival and durable clinical responses would benefit mTNBC patients. Then, we summarize the possible influencing factors of the interaction between tislelizumab and eribulin.

ObjectiveThe goal of this study is to compare the cost-effectiveness of tislelizumab and sorafenib as first-line treatment for advanced hepatocellular carcinoma in China.MethodsA comprehensive cost-effectiveness analysis was undertaken within the framework of a partitioned survival model to accurately gage the incremental cost-effectiveness ratio (ICER) of tislelizumab compared to sorafenib. The model incorporated relevant clinical data and all survival rates were from RATIONALE-301 trials. The stability of the partitioned survival model was assessed by performing one-way and two-way sensitivity analyses.ResultsThe total cost incurred for the tislelizumab treatment was $16181.24, whereas the sorafenib was $14306.87. The tislelizumab regimen resulted in a significant increase of 0.18 quality-adjusted life years (QALYs) and an extra cost of $1874.37 as compared to chemotherapy. The ICER was $10413.17 per QALY, which was found to be below the willingness-to-pay (WTP) threshold of $37304.34/QALY. The results of the sensitivity analysis found that no fluctuations in any of the factors affected our results, even when these parameters fluctuated.ConclusionTislelizumab appears to be a cost-effective first-line treatment for advanced hepatocellular carcinoma when compared to sorafenib in China. These findings can inform decision-making processes regarding the selection of the most cost-effective treatment option for advanced hepatocellular carcinoma.

BackgroundTislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody has been approved in China and Europe. According to the published clinical research, tislelizumab shows satisfactory safety profile. No severe hepatotoxicity or acute kidney injury were reported.Case presentationWe presented a case study of a 74-year-old man who developed acute kidney injury (grade 3) and acute liver injury (grade 4) after being administered tislelizumab for the treatment of esophageal squamous cell carcinoma. We reviewed the patient’s history, physical examination, and laboratory findings and provided comprehensive differentials of the possible causes of the toxicities. Immune Checkpoint Inhibitors (ICI) hepatotoxicity and nephrotoxicity were confirmed clinically. We also discussed the management of toxicities associated with ICIs and the need for a multidisciplinary approach to care.ConclusionsThe case highlights the importance of close monitoring and prompt management of toxicities associated with ICIs and the need for further research to better understand the risk factors for these toxicities and to identify effective treatments for them.

Chongchong Zhou,1,2,&ast; Jingxuan Wei,1,&ast; Kai Xu,1 Yingtao Lin,3,4 Lingli Zhang,1 Xin Li1,4,5 1Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Research Management, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Department of Drug Clinical Trial Institution, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 4Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Health Policy, School of Health Policy and Management, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Li; Lingli Zhang, School of Pharmacy, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, People’s Republic of China, Email xinli@njmu.edu.cn; zhanglingli@njmu.edu.cnBackground: Tislelizumab plus chemotherapy improved overall survival compared to chemotherapy alone, while maintaining an acceptable level of safety. But it’s still unclear which strategy is the most cost-effective. The objective of the study was to compare the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) versus chemotherapy alone.Methods: A partitioned survival model with three states was constructed based on the RATIONALE-306 trial. The model’s time horizon was ten years, and its cycle was three weeks. Only direct medical costs were considered from the healthcare perspective in China. Calculations were performed on total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity and probabilistic sensitivity analysis (PSA) were performed to determine the uncertainty regarding model parameters.Results: Tislelizumab plus chemotherapy provided 1.35 QALYs for &dollar;26,450.77, while chemotherapy alone provided 0.89 QALY for &dollar;16,687.15. Compared to chemotherapy alone, tislelizumab had an ICER of &dollar;21,062.09/QALY. At the threshold of three times the Chinese GDP per capita (&dollar;38,253/QALY), the PSA indicated that tislelizumab had a 96.4% likelihood of being designated cost-effective. At the threshold of 1.5 times the Chinese GDP per capita (&dollar;19,126.5/QALY), the PSA indicated that tislelizumab had a probability of 48.7% of being designated cost-effective.Conclusion: Tislelizumab plus chemotherapy as the first treatment for patients with advanced or metastatic ESCC may be a cost-effective option compared to chemotherapy alone at 3 times Chinese GDP per capita.Keywords: esophageal squamous cell carcinoma, cost-effectiveness, partitioned survival model, tislelizumab

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.

Riccardo Carloni,1,2 Simone Sabbioni,1,2 Alessandro Rizzo,3 Angela Dalia Ricci,4 Andrea Palloni,1,2 Cataldo Petrarota,3 Antonio Cusmai,3 Simona Tavolari,1,2 Gennaro Gadaleta-Caldarola,5,&ast; Giovanni Brandi1,2,&ast; 1Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy; 2Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Bari, Italy; 4Medical Oncology Unit, National Institute of Gastroenterology, “Saverio de Bellis” Research Hospital, Bari, Italy; 5Unità Operativa Complessa di Oncologia Medica, Ospedale “Mons. A.R. Dimiccoli”, Barletta, Italy&ast;These authors contributed equally to this workCorrespondence: Alessandro Rizzo, Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, Bari, 70124, Italy, Tel +39-051-2144078, Fax +39-051-6364037, Email rizzo.alessandro179@gmail.comAbstract: Hepatocellular carcinoma (HCC) is the fourth most frequent cause of cancer-related death worldwide. HCC frequently presents as advanced disease at diagnosis, and disease relapse following radical surgery is frequent. In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC, particularly with the introduction of atezolizumab/bevacizumab as the new standard of care for first-line treatment. Recently, dual immune checkpoint blockade with durvalumab plus tremelimumab has also emerged as an effective first-line treatment for advanced HCC and most of the research is currently focused on developing combination treatments based mainly on ICIs. In this review, we will discuss the rationale and ongoing clinical trials of immune-based combination therapies for the treatment of advanced HCC, also focusing on new immunotherapy strategies such as chimeric antigen receptor T cells (CAR-T) and anti-cancer vaccines.Keywords: hepatocellular carcinoma, VEGF, PD-1, tislelizumab, atezolizumab, durvalumab

Song Chen,1 Feng Shi,2 Zhiqiang Wu,3 Liguang Wang,4 Hongjie Cai,3 Ping Ma,5 Yuanmin Zhou,5 Qicong Mai,2 Fan Wang,3 Shuangyan Tang,3 Wenquan Zhuang,3 Jiaming Lai,6 Xiaoming Chen,2 Huanwei Chen,4 Wenbo Guo3 1Department of Minimally Invasive Interventional Therapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China; 3Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China; 5Department of Oncology, the Twelfth People’s Hospital of Guangzhou, Guangzhou, People’s Republic of China; 6Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Huanwei Chen, Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China, Email chwei_fsyyy@163.com Wenbo Guo, Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China, Email guowenbo@mail.sysu.edu.cnPurpose: The current therapeutic strategies for high-risk, unresectable hepatocellular carcinoma (HCC) patients demonstrate suboptimal outcomes. This study aimed to assess the clinical efficacy of the combined approach of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab, either with or without transhepatic arterial embolization (TAE), in managing HCC patients with portal vein tumor thrombus (PVTT) and significant tumor load.Patients and Methods: In this multicenter retrospective study, we analyzed patients diagnosed with primary, unresectable HCC presenting with PVTT and substantial tumor load who had undergone treatment with HAIC, lenvatinib, and tislelizumab, with or without TAE (referred to as the THLP or HLP group), between January 2019 and February 2022 across four medical centers in China. The outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).Results: The study cohort comprised 100 patients, 50 each in the THLP and HLP groups. The THLP group demonstrated a significantly superior ORR (72% vs 52%, P=0.039). However, both groups exhibited comparable DCR (88% vs 76%, P=0.118), as assessed by the modified response evaluation criteria in solid tumors. The median OS and PFS for the entire cohort were 12.5 months (95% CI, 10.9– 14.8) and 5.0 months (95% CI, 4.2– 5.4), respectively. The THLP group exhibited a significantly extended OS (median, 14.1 vs 11.3 months, P=0.041) and PFS (median, 5.6 vs 4.4 months, P=0.037) in comparison to the HLP group. The most frequently reported treatment-related adverse events included abdominal pain and nausea, both reported by 59% of patients.Conclusion: The combination of HAIC, lenvatinib, tislelizumab, and TAE was feasible in HCC patients with PVTT and high tumor burden, with tolerable safety.Keywords: hepatocellular carcinoma, transhepatic arterial embolization, hepatic arterial infusion chemotherapy, lenvatinib, tislelizumab

Abstract Aim This study was aimed to evaluate the safety and the efficacy of gemcitabine and oxaliplatin (GEMOX) combined with donafenib plus tislelizumab as the first‐line treatment for patients with unresectable biliary tract cancer (BTC). Methods This is a prospective single‐center exploratory study. Eligible patients (Stage III/IV BTC, at least one measurable disease according to RECIST v1.1, etc.) received gemcitabine 1000 mg/m2 IV Q3W, oxaliplatin 100 mg/m2 IV Q3W, donafenib 200 mg PO BID, and tislelizumab 200 mg IV Q3W until disease progression, unacceptable toxicity, or withdrawal of consent whichever occurred first. The primary endpoint was safety and secondary endpoints included disease control rate (DCR), objective response rate (ORR), conversion rate, and overall survival (OS). Results A total of 13 patients were enrolled. The median follow‐up time was 420 days (range 345–487). The median duration of treatment was four cycles (range 1–15). The incidence of ≥Grade 3 treatment‐related adverse events (TRAEs) was 53.8% and no Grade 5 TRAE. The most frequent Grade 3–4 TRAEs were rash (4/13, 30.8%), platelet count decreased (2/13, 15.4%), and fatigue (2/13, 15.4%). Tumor response was assessed in eight evaluable patients; ORR was 25.0% (95% CI, 3.2%–65.1%) and DCR 87.5% (95% CI, 47.3%–99.7%). The median PFS was 4.8 months (95% CI, 1.25‐NE). Three Stage III patients underwent subsequent surgery with a conversion rate of 23.1%. The median OS was not estimable. Conclusions GEMOX combined with donafenib plus tislelizumab as the first‐line therapy for unresectable BTC showed manageable toxicity and encouraging efficacy especially in terms of promising conversion rate in Stage III patients.

BackgroundGallbladder neuroendocrine carcinoma (GB-NEC) is an extremely rare cancer with a poor prognosis in the clinic. Although surgical resection remains the primary and preferred therapeutics, many patients are in a late stage and lose the opportunity for surgery. However, due to the extremely low morbidity, the specific treatment guidelines for GB-NEC have not been established.Case presentationA 52-year-old woman was admitted to our hospital with the chief complaint of “almost 1 month after palliative surgery for metastatic gallbladder carcinoma.” According to the results of pathological findings and imaging manifestations, the patient was diagnosed with GB-NEC with a clinical stage of pT3N1M1 (IVB). The patient then received tislelizumab plus EP chemotherapy (etoposide 100 mg + cisplatin 30 mg, d1–3) every 3 weeks for 8 cycles from 12 November, 2021, followed by maintenance therapy (tislelizumab alone) every 3 weeks until now. The tumor response was evaluated as complete remission since 13 February, 2023. As of the last follow-up, the patient remains alive, with no complaints of discomfort.ConclusionsGallbladder NEC has no specific symptoms, and the diagnosis is based on pathological and immunohistochemical results. The therapeutic course and efficacy of the case in this study indicates that the application of PD-1 inhibitor might be a feasible therapeutic option for GB-NEC. However, this potential strategy needs validation by further clinical studies in the future.

ObjectivesThe 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 methodsFifteen 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 PD-L1 expression and gene mutation.ResultsAt 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.ConclusionCombination therapy involving tislelizumab plus nimotuzumab is a promising, low-toxicity treatment for recurrent or metastatic OSCC in patients with a PS score ≥ 2.

As an immune checkpoint inhibitor (ICI), tislelizumab is an anti-programmed cell death protein 1 (PD-1) drug. With the extensive application of ICIs, there is an ever-increasing proportion of immune-related adverse events (irAEs) in clinical settings, some of which may even be life-threatening. Herein, we present a patient with tislelizumab-induced adrenal crisis. The main clinical manifestation was recurrent syncope accompanied by high-grade fever. Timely identification and hormone replacement therapy helped the patient overcome the crisis well. Finally, the patient discontinued tislelizumab and switched to antibody–drug conjugate (ADC) therapy. We report this case to improve our understanding of this situation, identify this kind of disease, and prevent adrenal crisis in time. Eventually, limiting toxicities reduces the interruption of immunotherapy. Since irAEs are multisystem damage with more non-specific symptoms, except for oncologists, general practitioners who endorse the need for taking a holistic approach to the patient should play a vital role in the management of cancer treatment.