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Drug-induced hyponatremia is an adverse reaction with accelerated electrolyte disturbance. This study reported a rare case of delayed hyponatremia in a 68year-old female with recurrent upper tract urothelial carcinoma after Gemcitabine plus Cisplatin (GC) and Tislelizumab treatment. She had left ureter surgery, recurrence a year later with mildly abnormal kidney function (glomerular filtration rate (GFR) was 54.9 ml/min). After the first cycle of GC plus Tislelizumab, severe hyponatremia leading to life-threatening conditions occurred eight days later. Hypothesizing Cisplatin as the cause, its usage was modified in the second cycle (40mg/day for three days). No severe hyponatremia followed. CT showed partial remission. From the third cycle, due to grade IV bone marrow suppression, she had Tislelizumab alone. Now, she is on 21-day Tislelizumab maintenance with a stable tumor status. Low-dose continuous Cisplatin may suit patients with borderline or mildly abnormal renal function (GFR: 40-60mL/min) better than single full-dose use. Tislelizumab alone for maintenance may be an option for those intolerant of chemotherapy. But Na+ decrease may be related to Tirelizumab or Gemcitabine, needing more clinical observation and experiments. [ABSTRACT FROM AUTHOR]

Objective: The RATIONALE-305 trial demonstrated that tislelizumab in combination with chemotherapy regimens was more beneficial than chemotherapy regimens alone in the treatment of patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC). This study aimed to evaluate the cost-effectiveness of tislelizumab combination chemotherapy in the treatment of advanced GC/GEJC from the perspective of the Chinese health service system. Methods: A three-state partition survival model was constructed to evaluate the economics of tislelizumab combined with chemotherapy as the first-line treatment of advanced GC/GEJC. Clinical data were collected from the RATIONALE-305 trial, and the incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life years (QALYs) as the output index. The stability of the results was verified using sensitivity and subgroup analyses. In addition, scenario analysis was conducted for the model simulation time and different parameter extrapolation models. Results: The results of basic analysis showed an increase of 0.31 QALYs in the tislelizumab group compared with the placebo group (1.53 QALYs vs 1.22 QALYs), and a concomitant increase in cost of 10,326.68 USD, with an ICER of 33,876.38 USD/QALY, which is less than the current Chinese willingness-to-pay threshold (36,924.80 USD/QALY). Sensitivity analyses demonstrated that the utility values of progression-free survival, progressive disease and the price of capecitabine had a greater impact on the model. Subgroup analysis revealed that combination therapy was equally cost-effective in people with a program death ligand 1 tumor area positivity score of ≥5%. Conclusion: From the perspective of the Chinese health service system, the treatment of advanced GC/GEJC with tislelizumab combined with chemotherapy has a cost-effective advantage over chemotherapy alone. [ABSTRACT FROM AUTHOR]

Tislelizumab, as a PD-1 inhibitor, has demonstrated significant efficacy in cancer treatment. However, it may also induce immune-related adverse events (irAEs). This case report describes a patient who developed oral ulcers and dysphagia following treatment with tislelizumab, which was diagnosed as exfoliative esophagitis through endoscopic examination. The condition improved after corticosteroid pulse therapy. A review of the relevant literature revealed no prior reports of immune checkpoint inhibitor (ICI)-related esophagitis cases, prompting an exploration of the potential pathophysiological mechanisms and therapeutic strategies. This report emphasizes the importance of vigilance for rare irAEs during ICI therapy, advocating for early detection and timely intervention. [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]

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. [ABSTRACT FROM AUTHOR]

Background: The 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 summary: A 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. Conclusion: In 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 FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and aim: The 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-FT treatment) for MSS-CRCLM which failed from multiple-line therapy. Methods: From 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. Results: The 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%). Conclusion: HAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy. [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.

Tislelizumab is a monoclonal antibody with high binding affinity for programmed death-1 (PD-1) receptors. In patients with extensive-stage small-cell lung cancer (ES-SCLC), the first-line use of tislelizumab combined with chemotherapy has shown significant efficacy. However, with the widespread use of PD-1 inhibitors, there are increasing reports of immune-related adverse events (irAEs) in clinical practice, with immune-related hepatitis (IRH) being particularly common. This article reports a case of an ES-SCLC patient (cT3N3M0 cStage IIIB) who developed corticosteroid-resistant hepatitis and recovered through dual immunosuppressant therapy. The patient was a 67-year-old male, diagnosed with ES-SCLC, who received a combination therapy of etoposide, cisplatin, and tislelizumab. Three weeks after the fourth treatment cycle, the patient experienced symptoms, such as decreased appetite, itching, yellow urine, and jaundice, and was diagnosed with IRH, manifested as “Grade 3 total bilirubin increase,” “Grade 3 alanine transaminase increase,” and “Grade 3 aspartate transaminase increase.” Despite intravenous injection of methylprednisolone (MP) 100 mg/day (2 mg/kg) and oral administration of mycophenolate mofetil (MMF) 1 g twice daily, liver function continued to be impaired. In this context, tacrolimus (TAC) (5 mg, twice daily) was added to the therapy, and the IRH level was reduced from Grade 3 to normal. Subsequently, TAC and MMF were gradually reduced and eventually discontinued. Unfortunately, after discontinuing immunosuppressants, IRH recurred. Although the patient still responded to TAC combined with MMF, liver function recovery took a longer time. Due to persistent liver dysfunction, the patient failed to receive second-line chemotherapy and ultimately passed away due to disease progression. Through this case, we hope to emphasize the importance of reasonably extending the use of immunosuppressants to avoid the recurrence of IRH and reduce the premature discontinuation of immunosuppressants. Besides, when tumor progression and IRH recurrence occur simultaneously, providing effective immunosuppressive therapy and reasonably arranging systemic anti-tumor therapy may bring clinical benefits to patients.

Drug-induced hyponatremia is an adverse reaction with accelerated electrolyte disturbance. This study reported a rare case of delayed hyponatremia in a 68year-old female with recurrent upper tract urothelial carcinoma after Gemcitabine plus Cisplatin (GC) and Tislelizumab treatment. She had left ureter surgery, recurrence a year later with mildly abnormal kidney function (glomerular filtration rate (GFR) was 54.9 ml/min). After the first cycle of GC plus Tislelizumab, severe hyponatremia leading to life-threatening conditions occurred eight days later. Hypothesizing Cisplatin as the cause, its usage was modified in the second cycle (40mg/day for three days). No severe hyponatremia followed. CT showed partial remission. From the third cycle, due to grade IV bone marrow suppression, she had Tislelizumab alone. Now, she is on 21-day Tislelizumab maintenance with a stable tumor status. Low-dose continuous Cisplatin may suit patients with borderline or mildly abnormal renal function (GFR: 40-60mL/min) better than single full-dose use. Tislelizumab alone for maintenance may be an option for those intolerant of chemotherapy. But Na+ decrease may be related to Tirelizumab or Gemcitabine, needing more clinical observation and experiments.

ObjectiveThe RATIONALE-305 trial demonstrated that tislelizumab in combination with chemotherapy regimens was more beneficial than chemotherapy regimens alone in the treatment of patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC). This study aimed to evaluate the cost-effectiveness of tislelizumab combination chemotherapy in the treatment of advanced GC/GEJC from the perspective of the Chinese health service system.MethodsA three-state partition survival model was constructed to evaluate the economics of tislelizumab combined with chemotherapy as the first-line treatment of advanced GC/GEJC. Clinical data were collected from the RATIONALE-305 trial, and the incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life years (QALYs) as the output index. The stability of the results was verified using sensitivity and subgroup analyses. In addition, scenario analysis was conducted for the model simulation time and different parameter extrapolation models.ResultsThe results of basic analysis showed an increase of 0.31 QALYs in the tislelizumab group compared with the placebo group (1.53 QALYs vs 1.22 QALYs), and a concomitant increase in cost of 10,326.68 USD, with an ICER of 33,876.38 USD/QALY, which is less than the current Chinese willingness-to-pay threshold (36,924.80 USD/QALY). Sensitivity analyses demonstrated that the utility values of progression-free survival, progressive disease and the price of capecitabine had a greater impact on the model. Subgroup analysis revealed that combination therapy was equally cost-effective in people with a program death ligand 1 tumor area positivity score of ≥5%.ConclusionFrom the perspective of the Chinese health service system, the treatment of advanced GC/GEJC with tislelizumab combined with chemotherapy has a cost-effective advantage over chemotherapy alone.

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 antiHER2 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 FROM AUTHOR]

Tislelizumab, as a PD-1 inhibitor, has demonstrated significant efficacy in cancer treatment. However, it may also induce immune-related adverse events (irAEs). This case report describes a patient who developed oral ulcers and dysphagia following treatment with tislelizumab, which was diagnosed as exfoliative esophagitis through endoscopic examination. The condition improved after corticosteroid pulse therapy. A review of the relevant literature revealed no prior reports of immune checkpoint inhibitor (ICI)-related esophagitis cases, prompting an exploration of the potential pathophysiological mechanisms and therapeutic strategies. This report emphasizes the importance of vigilance for rare irAEs during ICI therapy, advocating for early detection and timely intervention.

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.

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-yearold 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. [ABSTRACT FROM AUTHOR]

Background: Tislelizumab, 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 presentation: We 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. Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Background: Gallbladder 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 presentation: A 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 followup, the patient remains alive, with no complaints of discomfort. Conclusions: Gallbladder 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. [ABSTRACT FROM AUTHOR]

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: Bladder cancer with high expression of human epidermal growth factor receptor-2 (HER2) is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive urothelial bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph node dissection. For HER2-positive MIBC, the efficacy of cisplatin-based NAC is unsatisfactory, and adverse reactions are inevitable or even intolerable. New regimens with higher efficiency and lower toxicity need to be explored in the neoadjuvant setting for this population. Methods: HOPE-03 is a multi-center, open-label, single-arm, phase Ib/II study aiming to evaluate the safety and efficacy of RC48-ADC (disitamab vedotin (DV)), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab (PD-1 antibody) as a novel neoadjuvant treatment combination in patients with HER2-positive locally advanced urothelial MIBC. Fifty-one patients with cT2-4bN0-3M0-1a pathology- and imaging-diagnosed HER2 positive (immunohistochemistry status 3+ or 2+ or 1+) MIBC were recruited. Of these patients, six were enrolled in the dose-escalation phase (three patients in the RC48-ADC 1.5 mg/kg group and three patients in the 2.0 mg/kg group), and 45 patients were enrolled in the phase II study (the expected recommended phase II dose for RC48-ADC was 2.0 mg/kg). Patients without disease progression received radical cystectomy or bladder-sparing therapies as their preference after neoadjuvant treatment. The primary endpoints were clinical complete remission rate (cCR rate; T0/Ta/Tis), pathological complete remission rate (pCR rate), and safety. The secondary endpoints were overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and quality of life. Discussion: The HOPE-03 trial provides a description of the safety profile of RC-48 and tislelizumab combination in the neoadjuvant treatment of HER2-positive locally advanced urothelial MIBC, and the efficacy is explored as well in this population. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have made significant breakthroughs in the treatment of a variety of malignancies. As its use increases, the unique immunemediated toxicity profile of ICls are becoming apparent. We report a case of immune-related endocrine adverse events (irAE) in a patient with hepatocellular carcinoma treated with anti-programmed cell death protein 1 (PD-1) (tislelizumab). Although many irAEs have been reported, few cases of severe thyrotoxicosis have been described after immunotherapy in the literature. We present the case of a 49-year-old male who experienced a Grade 3 tislelizumabrelated adverse reaction according to Common Terminology Criteria for Adverse Events (CTCAE5.0) and received methylprednisolone, thiamazole, and levothyroxine sodium tablets. Early identification of irAEs, risk factors, regular monitoring, use of steroids and/or immunoglobulins, and adjuvant supportive care are critical to the clinical prognosis of patients. It should be underlined that the tumor benefits of ICI therapy outweigh the risks associated with ICI-induced endocrine disorders, and ICI treatment should not be stopped or delayed except in rare cases (adrenal crisis, severe thyrotoxicosis). The familiarity of healthcare professionals with irAEs of the thyroid when thyrotoxicosis occurs is important to facilitate an effective diagnosis and appropriate treatment of this increasingly common thyroid disorder. [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]

The prognosis for patients with advanced gastric cancer (AGC) is poor, with limited treatment options available due to the difficulty of resection. In recent years, chemotherapy and immunotherapy for AGC have shown promising efficacy. However, there is a controversy regarding the surgery of primary tumors and/or metastases in patients with stage IV gastric cancer after systematic therapy. Here, we present a 63-year-old retired female of AGC with supraclavicular metastasis with positive PD-L1 and tumor mutational burdenhigh (TMB-H). After receiving 8 cycles of capecitabine and oxaliplatin (XELOX) in combination with tislelizumab, the patient achieved complete remission (CR). No evidence of recurrence was identified during follow-up. To the best of our knowledge, this is the first case of AGC with supraclavicular metastasis who achieved CR after treatment with tislelizumab. The mechanism of CR was discussed by genomic and recent clinical studies. The results indicated that programmed death ligand-1 (PD-L1) combined positive score (CPS) =5 may serve as a clinical indication and standard for chemo-immune combination therapy. In combination with other similar reports, patients with microsatellite instabilityhigh/defective mismatch repair (MSI-H/dMMR), (TMB-H), and positive PD-L1 had better sensitivity to tislelizumab. The patient recovered successfully except for symptoms of gastrointestinal hemorrhage during treatment, which may be associated with the treatment cycle and age. Immunotherapy with tislelizumab has been well-established in the treatment of malignant melanoma, lung cancer, and clear-cell kidney cancer, but its efficacy and safety for esophageal and gastric cancers remain to be validated. The CR of our patient suggested the prospects of tislelizumab in the immunotherapy of gastric cancer. Additionally, a watch-and-wait (WW) method maybe offered for patients with AGC who achieved complete clinical remission (CCR) after immune combination therapy if the patient was older or in poor physical condition. [ABSTRACT FROM AUTHOR]

Second-line treatment for metastatic or locally advanced urothelial cancer (UC) is limited. Immunotherapy is approved as a second-line treatment for metastatic UC. Its use as a first-line agent is limited to patients who are ineligible for cisplatin-based treatments. The fibroblast growth factor receptor (FGFR) inhibitor, erdafitinib, can be applied as a third-line approach after the failure of these prior treatments in eligible patients. Therefore, it is especially important to combine limited drugs for second-line treatment of advanced or metastatic UC. Anlotinib is a multiple tyrosine kinase inhibitor agent with both anti-angiogenic and FGFR inhibitory effects. For two patients with advanced and metastatic UC, we combined anlotinib and tislelizumab therapy even though there is no indication of its use. We describe two patients with programmed death ligand-1 (PD-L1)-negative advanced bladder cancer, one with FGFR3 mutation and another with FGFR3 wild type. Both patients had progressed after first-line chemotherapy with gemcitabine and cisplatin. We selected anlotinib in combination with tislelizumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, for second-line treatment. Responses were evaluated as partial remission in both cases, who achieved up to 12 months of progressionfree survival with no significant adverse events. Two patients with PD-L1-negative UC underwent second-line therapy using tislelizumab in combination with anlotinib, and the efficacy was better than that of tislelizumab alone. These results suggest that anlotinib may act synergistically with tislelizumab in the treatment of UC. [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: Muscle invasive bladder urothelium carcinoma is a common urinary tract tumor. With the deepening of research, more and more treatment methods are applied in clinical practice, extending the life of patients. Among them, the clinical application of chemotherapeutic intravesical hyperthermia and tumor immunotherapy provides new ideas for our treatment. Case report: An 81-year-old female patient was diagnosed with stage T2N0M0 bladder cancer in our hospital. Because the patient and her family were keen to preserve her bladder, they declined surgery and opted for combined chemotherapy. After informed consent from the patient and her family, she received cisplatin combined with gemcitabine intravesical hyperthermic infusion. But the side effects of cisplatin made her intolerable to chemotherapy. With their informed consent we changed her to intravenous tislelizumab in combination with gemcitabine intravesical hyperthermic infusion to continue her treatment. During the subsequent follow-up visits, we found a surprising effect of the treatment. Conclusion: Gemcitabine intravesical hyperthermia therapy combined with intravenous tislelizumab in the treatment of muscle invasive bladder urothelium carcinoma may provide a new possible therapeutic strategy of some patients who are inoperable or refuse surgery. [ABSTRACT FROM AUTHOR]

Despite the intriguing therapeutic prospects offered by immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs) become an increasingly important safety issue. Herein, we report a patient with locally advanced colorectal cancer (LACRC) who received anti-programmed cell death protein 1 (PD-1) (tislelizumab) therapy, then developed weakness of the limbs and drooping eyelids. He experienced sequential irAEs including severe myasthenia gravis, myocarditis, and rhabdomyolysis. Although many irAEs caused by tislelizumab have been reported, the cooccurrence of severe myasthenia gravis, myocarditis, and rhabdomyolysis caused by tislelizumab has not been described. The patient responded well to methylprednisolone and intravenous immunoglobulin therapy. This case illustrates the severe toxicity caused by ICIs, highlighting the importance of early prevention, early diagnosis, and appropriate management of irAEs. Multidisciplinary discussions should be held to improve the prognosis of patients.

Background: Renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation is a very dangerous malignant tumor and extremely rare in clinical practice. In general, these tumors with a dismal prognosis, and there is no standard treatment. Case presentation: In this case, an 81-year-old male patient was diagnosed with r ight renal pelvic carcinoma. After an open right radical nephroureterectomy, postoperative pathological examination showed infiltrating urothelial carcinoma with sarcomatoid differentiation. Overexpression of programmed death ligand-1 by immunohistochemistry. The carcinoma recurred 4.5 months after surgery. After informed, tislelizumab combined with anlotinib were used as first-line treatment. The patients showed a clinical partial response that lasted for 20 months. Conclusion: This case demonstrates the efficacy of tislelizumab combined with anlotinib in patients diagnosed with metastatic renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation. Moreover, to our knowledge, this is the first application of this treatment. [ABSTRACT FROM AUTHOR]

Background: Recently, the combination of immunotherapy with chemotherapy has been recommended as first-line treatment of metastatic gastric/gastroesophageal junction (G/GEJ) in the clinical guidelines of many countries; the therapeutic potential of this application needs to be further investigated for neoadjuvant therapy of advanced G/GEJ cancer patients. Methods: We performed a prospective, single-arm, open-label, phase 2 trial of the PD-1 inhibitor tislelizumab combined with S-1 plus oxaliplatin (SOX) in patients with advanced LAG/GEJ cancer. All patients underwent the threecycle (21 days/cycle) treatment except for one patient who underwent two cycles. The primary endpoints were tumor major pathology response (MPR) and other events of tumor response assessed by the RECIST 1.1 and Becker criteria. Moreover, we constructed a few-shot learning model to predict the probability of MPR, which could screen those patients who might benefit from the neoadjuvant immunotherapy-chemotherapy scheme. This study was registered at https://clinicaltrials.gov/ct2/show/NCT0-4890392. Results: Thirty-two patients were enrolled; 17 patients (53.1%) achieved MPR (=10% viable tumor cells) after treatment, and among them, 8 (25.0%) had a pathological complete response (pCR). The 1-year overall survival (OS) rate was 91.4% and the 1-year recurrence-free survival (RFS) rate was 90.0%. Adverse events occurred in 24 patients (65.6%) and grade III-IV adverse events were observed in 4 patients (12.5%) during the neoadjuvant period. Furthermore, we found commonly used preoperative assessment tools such as CT and EUS, which presented limited accuracy of tumor therapeutic response in this study; thus, we developed a therapeutic response predictive model that consisted of TNFa, IFNg, IL-10, CD4, and age of patient, and the AUC of this FSL model was 0.856 (95% CI: 0.823-0.884). Discussion: Our study showed that the neoadjuvant PD-1 inhibitor tislelizumab combined with SOX had promising application potential and presented no increasing treatment-related adverse events in patients with advanced G/GEJ cancer. Moreover, the predictive model could help therapists to evaluate the therapeutic response of this scheme accurately. [ABSTRACT FROM AUTHOR]

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.

Recurrence of urothelial carcinoma in a patient with solitary kidney is always a clinical challenge. In the immune checkpoint inhibitor era, neoadjuvant immunotherapy in combination with the Yang-Monti technique might be a good option for the patient with a high-risk tumor when kidney-sparing surgery for renal function preservation is desired. We report the case of a 74-year-old man with solitary kidney who was diagnosed with recurrence of urothelial carcinoma in the right ureter. He was initially deemed unfit for segmental resection of the ureter. Neoadjuvant immunotherapy with tislelizumab was performed in this patient with a partial response to urothelial carcinoma. He underwent segmental resection of the ureter with negative margins, and the ureteral defect was bridged by modified ileal replacement, which is the Yang-Monti technique. This patient has remained disease-free with adequate kidney function for longer than 18 months. [ABSTRACT FROM AUTHOR]

Background: Tislelizumab combined with radiotherapy as a salvage treatment for patients with end-stage metastatic castration-resistant prostate cancer (mCRPC) is not reported. This study aimed to describe a protocol to evaluate the safety and efficacy of multisite radiotherapy combined with tislelizumab as a salvage therapy for mCRPC in patients who had at least one second-line treatment failure. Methods: The study included patients with mCRPC who had at least one lesion suitable for radiotherapy and failed androgen deprivation therapy (ADT), followed by at least one novel second-line endocrine therapy. All patients received tislelizumab monotherapy induction therapy for two cycles, then combined with multisite radiotherapy for one cycle, followed by tislelizumab maintenance therapy, until either disease progressed or the patient developed unacceptable toxicity. Radiation methods and lesions were individually selected according to the specified protocol. Primary endpoints included safety and objective response rate. Secondary endpoints included prostate-specific antigen (PSA) response rate, disease control rate, overall survival, radiographic progression-free survival (rPFS), and biochemical progression-free survival (bPFS). Furthermore, the exploratory endpoints included the identification of the predictive biomarkers and exploration of the correlation between biomarkers and the tumor response to the combined regimen. Discussion: This study included three treatment stages to evaluate the efficacy of immunotherapy and the combination of immunotherapy and radiotherapy for patients with mCRPC who have had at least second-line treatment failure. Additionally, radiation-related and immune-related early and late toxicities were determined, respectively. Furthermore, the study also aimed to identify the predictive biomarkers associated with immunotherapy for treating mCRPC. Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=126359, identifier ChiCTR2100046212. [ABSTRACT FROM AUTHOR]

The discovery of immune checkpoint inhibitors (ICIs) represents a significant step forward in the battle against malignant tumors. In a number of advanced malignancies, ICIs, such as antibodies to programmed cell death protein-1 inhibitor (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), have shown good therapeutic benefits. A 71-year-old male patient was diagnosed with solitary renal calyceal urothelial cancer. The space-occupying lesion in the upper calyx of the left kidney dramatically decreased after 13 treatments with a PD-1 inhibitor (tislelizumab) alone, and the tumor reached partial remission. This case suggests that a PD-1 inhibitor (tislelizumab) alone may be an effective treatment strategy for solitary renal calyceal urothelial carcinoma. [ABSTRACT FROM AUTHOR]

The discovery of immune checkpoint inhibitors (ICIs) represents a significant step forward in the battle against malignant tumors. In a number of advanced malignancies, ICIs, such as antibodies to programmed cell death protein-1 inhibitor (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), have shown good therapeutic benefits. A 71-year-old male patient was diagnosed with solitary renal calyceal urothelial cancer. The space-occupying lesion in the upper calyx of the left kidney dramatically decreased after 13 treatments with a PD-1 inhibitor (tislelizumab) alone, and the tumor reached partial remission. This case suggests that a PD-1 inhibitor (tislelizumab) alone may be an effective treatment strategy for solitary renal calyceal urothelial carcinoma.

Immune-related adverse events (irAEs) following treatment with immune checkpoint inhibitors (ICIs) can affect almost any organ systems. Multiple-organs irAEs are a rare occurrence which makes its management and treatment very challenging. This is a case report of a 71-year-old man with advanced non-small cell lung cancer (NSCLC) who developed multiple-organs irAEs (lung, muscle, myocardium, liver, and pituitary) after a single cycle (21 days) of the BGB-A317 (Tislelizumab). After more than two months of immunosuppression treatment with glucocorticoids, the tumor and inflammatory lesions in the lung were reduced. The levels of serum creatase, cardiac troponin T (TNT), and hepatic transaminase were also reduced. Four months after the termination of ICI therapy, the lung tumor reappeared in the previous site. This rare case report supplies several experiences in the management of multiple-organs irAEs, including full-scale monitoring of immunological indicators, early differential diagnosis, and prompt glucocorticoid therapy. This patient was not a candidate for the ICI re-challenge therapy due to the number and seriousness of irAEs. Multiple-organs irAEs add complexity to the management, and additional research is needed to develop optimal therapeutic guidelines.

Immune-related adverse events (irAEs) following treatment with immune checkpoint inhibitors (ICIs) can affect almost any organ systems. Multiple-organs irAEs are a rare occurrence which makes its management and treatment very challenging. This is a case report of a 71-year-old man with advanced non-small cell lung cancer (NSCLC) who developed multiple-organs irAEs (lung, muscle, myocardium, liver, and pituitary) after a single cycle (21 days) of the BGB-A317 (Tislelizumab). After more than two months of immunosuppression treatment with glucocorticoids, the tumor and inflammatory lesions in the lung were reduced. The levels of serum creatase, cardiac troponin T (TNT), and hepatic transaminase were also reduced. Four months after the termination of ICI therapy, the lung tumor reappeared in the previous site. This rare case report supplies several experiences in the management of multiple-organs irAEs, including full-scale monitoring of immunological indicators, early differential diagnosis, and prompt glucocorticoid therapy. This patient was not a candidate for the ICI re-challenge therapy due to the number and seriousness of irAEs. Multiple-organs irAEs add complexity to the management, and additional research is needed to develop optimal therapeutic guidelines. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-associated lymph nodal T/NK cell lymphoma (nodal TNKL) is a rare and aggressive malignancy with an extremely poor prognosis. Although treatments of extranodal NK/T cell lymphoma are frequently reported, the characteristics and pathogenesis of EBV-associated nodal TNKL are different. However, there is no known effective therapy regimen at present. Here, we reported the clinical efficacy and feasibility of the programmed death 1 (PD-1) blockade therapy regimen in an elderly female patient with EBV-associated nodal TNKL. The patient failed to respond to cyclophosphamide, doxorubicin, vindesine, and prednisone regimen but achieved complete response after three cycles of anti-PD-1 antibody (tislelizumab) combined with gemcitabine and oxaliplatin (GemOx) regimen. The finding indicated that tislelizumab combined with the GemOx regimen may be a potent salvage regimen for EBV-associated nodal TNKL.

Epstein-Barr virus (EBV)-associated lymph nodal T/NK cell lymphoma (nodal TNKL) is a rare and aggressive malignancy with an extremely poor prognosis. Although treatments of extranodal NK/T cell lymphoma are frequently reported, the characteristics and pathogenesis of EBV-associated nodal TNKL are different. However, there is no known effective therapy regimen at present. Here, we reported the clinical efficacy and feasibility of the programmed death 1 (PD-1) blockade therapy regimen in an elderly female patient with EBV-associated nodal TNKL. The patient failed to respond to cyclophosphamide, doxorubicin, vindesine, and prednisone regimen but achieved complete response after three cycles of anti-PD-1 antibody (tislelizumab) combined with gemcitabine and oxaliplatin (GemOx) regimen. The finding indicated that tislelizumab combined with the GemOx regimen may be a potent salvage regimen for EBV-associated nodal TNKL. [ABSTRACT FROM AUTHOR]

IntroductionTransarterial chemoembolization (TACE) is inefficient at converting unresectable hepatocellular carcinoma (uHCC) to resectable. Treatment with immune checkpoint inhibitors (ICIs) is an emerging strategy for uHCC. Combined therapy of TACE with ICIs is considered to improve the therapeutic effect.Case presentationA 45-year-old man was diagnosed with a bulky HCC under cirrhotic background without distant metastasis. Curative resection was infeasible, and TACE plus tislelizumab (an ICI targeting PD-1) was applied. The treatment course, starting from TACE and followed by tislelizumab one week later, was repeated every four weeks. After three courses, the tumor showed striking shrink in volume with complete radiological response, which permitted salvage resection. Notably, pathological examination found complete necrosis of the tumor with massive infiltration of lymphocytes in the tumor-nontumor interface and extensive granulomatous inflammation in the surrounding nontumor liver, indicating activated immune response synergistically caused by TACE with tislelizumab. The patient is now living well without tumor recurrence for 6 months after surgery.ConclusionTACE in combination with tislelizumab may represent a potent strategy for uHCC. Data from randomized clinical trials are needed to assess its safety and effect in the setting of preoperative downstaging therapy.

Introduction: Transarterial chemoembolization (TACE) is inefficient at converting unresectable hepatocellular carcinoma (uHCC) to resectable. Treatment with immune checkpoint inhibitors (ICIs) is an emerging strategy for uHCC. Combined therapy of TACE with ICIs is considered to improve the therapeutic effect. Case presentation: A 45-year-old man was diagnosed with a bulky HCC under cirrhotic background without distant metastasis. Curative resection was infeasible, and TACE plus tislelizumab (an ICI targeting PD-1) was applied. The treatment course, starting from TACE and followed by tislelizumab one week later, was repeated every four weeks. After three courses, the tumor showed striking shrink in volume with complete radiological response, which permitted salvage resection. Notably, pathological examination found complete necrosis of the tumor with massive infiltration of lymphocytes in the tumor-nontumor interface and extensive granulomatous inflammation in the surrounding nontumor liver, indicating activated immune response synergistically caused by TACE with tislelizumab. The patient is now living well without tumor recurrence for 6 months after surgery. Conclusion: TACE in combination with tislelizumab may represent a potent strategy for uHCC. Data from randomized clinical trials are needed to assess its safety and effect in the setting of preoperative downstaging therapy. [ABSTRACT FROM AUTHOR]