Checkpoint inhibitor pneumonitis (CIP) is a potentially fatal disease that can occur at any duration of treatment. Patients may present with vague respiratory symptoms such as progressive cough, dyspnea, and decreased activity tolerance. Among checkpoint inhibitors, CIP is higher in programmed death 1 (PD-1) inhibitors. An 82-year-old Latina woman with estrogen receptor (ER)-positive human epidermal growth factor receptor (HER)-2-negative lobular carcinoma of the right breast had been treated by partial mastectomy followed by adjuvant hormonal treatment and radiation in 2014. Then CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) was followed by letrozole and abemaciclib, PD-1, therapy in 2022. In 2023, the patient presented with a dry cough and worsening dyspnea with a new oxygen requirement. She was admitted to the hospital with a diagnosis of multifocal pneumonia and sepsis. She unfortunately developed rapidly higher oxygen requirements and acute respiratory distress syndrome (ARDS) and was ultimately presumed to have CIP. She was intubated on hospital day 6 and extubated on day 12 with no plans for reintubation and do-not-resuscitate status. She subsequently had demise after a period of respiratory arrest. CIP is rare but associated with fatal outcomes, especially with the development of ARDS. It is important, along the course of cancer treatment and goals of care discussion, to educate patients and their families on possible side effects of chemotherapy and involve specialists early with the goal of lowering mortality rates. Most patients do not survive this unfortunate progression of disease.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Hepatic resection constitutes the major curative treatment option, but a significant proportion of patients are not surgical candidates on initial evaluation. Along with the development of novel therapeutic strategies including targeted therapies and immunotherapies, a few HCCs can achieve tumor downstaging and be curatively resected. A 52-year-old man was diagnosed with HCC with portal vein invasion and extensive pulmonary and lymph node metastasis. Transarterial chemoembolization (TACE) in conjunction with donafenib and sintilimab was given. Primary tumors in the liver largely shrank with almost complete elimination of the lung metastases following treatment. The patient subsequently underwent curative surgery for HCC, and the pathological examination revealed complete necrosis of the tumor. Targeted immunotherapy was continued after surgery and no disease progression was found on the latest follow-up. Advanced HCC with distant metastasis might have an excellent response to combination therapy of TACE with tyrosine kinase-targeted inhibitors and PD-1 blocker, and achieve opportunity for curative surgery. This efficacy may be associated with the remodeling of immune microenvironment and angiogenesis. HCC is extremely heterogeneous, and the response to therapeutics varies among patients. There is a lack of useful biomarkers to predict therapeutic efficacy, which needs further studies.

UNASSIGNED: Esophageal Squamous Cell Carcinoma (ESCC) contributes to the global burden of disease. Conventional treatments such as surgical resection and chemotherapy offer limited long-term survival rates. Recently, immunotherapies targeting PD-1 have shown promise in other cancers, but their efficacy in ESCC remains unclear.
UNASSIGNED: The 31 studies eligible for this study included a total of 10,681 patients who were subjected to immunotherapy, either alone or in combination with traditional chemotherapy. A comprehensive search was conducted on September 1, 2023, across databases including CENTRAL, PubMed, MEDLINE, Web of Science, Embase, and Scopus.
UNASSIGNED: For OSR, results indicate a significantly improved survival at different time points (6, 12, and 24 months), with an odds ratio of 0.636 (95 % CI 0.595-0.680; Z = -13.292; p < 0.00001). In terms of PFS, PD-1 inhibitors demonstrated improvements at different time points; pooled odds ratio was 0.568 (95 % CI 0.511-0.633; Z = -10.357; p < 0.00001). Regarding ORR, the pooled analysis showed an overall odds ratio of 1.724 (95 % CI 1.554-1.913; Z = 10.289; p < 0.00001), indicating improved treatment response. DCR did not suggest a significant advantage for PD-1 inhibitors over chemotherapy, with an odds ratio of 0.904 (95 % CI 0.784-1.043; Z = -1.381; p = 0.167).
UNASSIGNED: There is compelling evidence reinforcing the efficacy and safety of PD-1 inhibitors, as monotherapy or in combination with chemotherapy, for the treatment of ESCC. PD-1 inhibitors demonstrate a significant advantage in terms of OSR, PFS, and ORR.

Melanoma is the fifth most common cancer in the United States and accounts for the majority of all skin cancer-related deaths, making it the most lethal cutaneous malignancy. Systemic adjuvant therapy for stage IIB-IV melanoma is now approved for patients who have undergone surgical resection, given the appreciable risk of recurrence and mortality in this patient population. Despite the lower stage, high-risk stage II melanoma (stage IIB/IIC) can often exhibit an even more aggressive course when compared to stage IIIA/IIIB disease, thus justifying consideration of adjuvant therapy in these patients. In this review, we highlight the current standard of practice for the treatment of stage IIB/C melanoma, with a focus on adjuvant therapies supported by published landmark clinical trials, including anti-PD-1 therapy. Notably, adjuvant therapies approved thus far in this patient population have demonstrated an improvement in recurrence-free survival, while their impact on overall survival is pending. Finally, this review highlights currently ongoing trials and future directions for research and treatment possibilities for high-risk clinical stage II melanoma.

UNASSIGNED: Recently, a sum of trials of programmed cell death-1 (PD-1) inhibitors combined with chemotherapy have shown excellent efficacy compared to chemotherapy alone in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no head-to-head comparison and consensus on which immunotherapy regimen results in better survival outcomes. This study aimed to evaluate the survival efficacy of various PD-1 inhibitor-based therapies in the first-line treatments for patients with advanced ESCC.
UNASSIGNED: Data collected prior to 31 July 2023 were searched in the PubMed, Cochrane Library, Embase, Medline, and Web of Science databases. Overall survival (OS) and progression-free survival curves were pooled using the MetaSurv package. Survival data were compared by reconstructed individual patient data.
UNASSIGNED: A total of 4,162 patients and seven randomized controlled trials were included. After synthesizing, PD-1 inhibitors prolonged median OS from 11.3 months (95% CI (confidence interval) 10.7-11.7) to 15.6 months (95% CI 14.7-16.3). Based on reconstructed patient-level data, the toripalimab, tislelizumab, and sintilimab group achieved the longest OS, whereas the sintilimab and tislelizumab group had the lowest risk of recurrence than other treatments. In patients with a combined positive score of ≥10, sintilimab had better OS efficacy than pembrolizumab (HR: 0.71, 95% CI: 0.52-0.96). In terms of tumor proportion score of ≥1%, camrelizumab, nivolumab, and toripalimab showed proximate survival benefits in both OS and progression-free survival.
UNASSIGNED: PD-1 inhibitor combined with chemotherapy significantly improved the survival time of patients with advanced ESCC. Toripalimab, tislelizumab, and sintilimab plus chemotherapy showed the best OS benefit. Longer progression-free benefits might be generated from adding tislelizumab and sintilimab to chemotherapy. Sintilimab was strongly recommended for patients with high programmed cell death-ligand 1 abundance.
UNASSIGNED: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42024501086].

Immunotherapy, led by programmed cell death protein-1 (PD-1) inhibitors, has emerged as a prominent antitumor therapy, yet prognostic challenges persist in pancreatic cancer (PC). This retrospective, single-center study evaluated prognostic factors in advanced PC patients treated with PD-1 inhibitors at the PLA General Hospital\'s Oncology Department from 2015-2022. With ethics approval by the Ethics Committee of the General Hospital of the People\'s Liberation Army (S2021-228-03), we analyzed 126 patients using Kaplan-Meier and Cox models. p < .05 was considered a statistically significant difference. Median overall survival (mOS) and progression-free survival (mPFS) were 12.1 and 4.6 months, respectively. Significant mOS predictors were surgery history (44.2 months vs. 10 months, *p = .022), absence of liver metastases (44.2 months vs. 6.4 months, *p = .034), and baseline CA19-9 ≤ 216.15 U/ml (18.5 months vs. 9.2 months, *p = .049). For mPFS, histologic differentiation (5.5 months vs. 3.2 months, *p = .022) and first-line PD-1 inhibitor use (5.1 months vs. 1.5 months, ***p = .001) were key. Subgroup analyses highlighted early progression in low histologic differentiation and earlier death without surgery. History of surgery, absence of liver metastases, baseline CA19-9 level, and histologic intermediate/high differentiation may predict PD-1 inhibitor efficacy in advanced PC, pending validation in prospective trials.

OBJECTIVE: To observe the clinical efficacy of Camrelizumab in patients with advanced cervical cancer who presented with resistance to initial therapy.
METHODS: We retrieved data from 25 patients with advanced (stage IIA2-IV) cervical cancer who were administered a combination salvage therapy with Camrelizumab due to the poor response to initial chemotherapy. The primary outcome was objective response rate (ORR) and disease control rate (DCR), the secondary endpoints included progression-free survival (PFS) and the occurrence of adverse events. To evaluate its long-term effect on PFS, we included 64 patients diagnosed with stage IIA2-IV during the study period, who were responsive to initial radiotherapy or chemotherapy and received conventional therapy as control.
RESULTS: Camrelizumab exhibits a high salvage treatment efficacy, with ORR of 80.0% (20/25) and DCR of 88.0% (22/25) in Camrelizumab salvage group (CS group). The PFS in CS group was significantly longer than that in control group. The median follow-up time were 18.1 and 18.3 months in the CS group and the control group, respectively, and neither achieved median PFS. The adverse event (AEs) rates in the CS and control groups were 52.0% (13/25) and 51.6% (33/64), in which the most common adverse events were myelosuppression, cutaneous capillary endothelial proliferation (CCEP), and elevated liver enzymes, and the grade of AEs was less than grade 3 in all patients.
CONCLUSIONS: Camrelizumab demonstrated promising efficacy and safety as the early salvage treatment for patients with advanced cervical cancer.

UNASSIGNED: Lung cancer is the leading cause of cancer-related death, and non-small-cell lung cancer (NSCLC) is the predominant subtype. Programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are widely used to treat stage IV NSCLC. This study systematically reviewed the literature to clarify the impact of PD-1/PD-L1 inhibitor treatment on the survival of patients with stage III NSCLC.
UNASSIGNED: Randomized phase III clinical trials of PD-1/PD-L1 inhibitors administered to patients with stage III NSCLC that were written in English and published between November 2012 and November 2022 were eligible for review. The sources of information were the MEDLINE database (last consulted on December 26, 2022), ScienceDirect website (last consulted on December 26, 2022), and CENTRAL register (last consulted on December 27, 2022). The outcomes of interest were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and event-free survival (EFS). Risk of bias assessments were performed according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. The findings have been assessed for certainty according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines.
UNASSIGNED: Fourteen eligible studies and 2788 participants were included in the review. The key characteristics used to group the participants were disease histology, percentage of PD-L1 expression in cancer cells, and timeline of therapy. OS and PFS were improved (risk ratio [RR]: 0.85; 95% confidence interval [CI]: 0.75-0.96 and RR: 0.75; 95% CI: 0.70-0.86, respectively) based on the use of PD-L1 inhibitors after chemoradiation and OS was improved using first-line PD-1 inhibitors plus chemotherapy in non-squamous NSCLC (RR: 0.40; 95% CI: 0.17-0.95), with the GRADE results indicating moderate quality of evidence.
UNASSIGNED: This review highlights the OS and PFS benefits of PD-L1 inhibitors in stage III NSCLC when used after chemoradiation and OS benefits of first-line PD-1 inhibitors added to chemotherapy in non-squamous stage III disease.

BACKGROUND: Lung cancer is the cancer with the highest incidence and mortality rates in China, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of all malignant lung tumors. Currently, surgical treatment remains the primary treatment modality for lung cancer. In recent years, the effectiveness of immune checkpoint inhibitors for NSCLC has become a consensus, and neoadjuvant immunochemotherapy (nICT) has shown promising efficacy and safety in early to intermediate stage NSCLC. However, there are fewer studies related to nICT for locally advanced NSCLC. This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC.
METHODS: 85 confirmed resectable stage IIIA and IIIB patients treated in the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from January 2021 to April 2024, were divided into the nICT group (n=32) and the surgery alone group (n=53). Clinical baseline data, perioperative indicators, postoperative complications, imaging response rate, pathological response rate, incidence of adverse events, and quality of life were compared between the two groups.
RESULTS: There were no statistically significant differences in clinical baseline data between the two groups (P>0.05). Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group (P=0.002). There were no significant differences in surgical time, intraoperative blood loss, number of dissected lymph nodes, duration of chest tube placement, postoperative hospital stay, and R0 resection rate between the two groups (P>0.05). The overall incidence of postoperative complications was 31.25% in the nICT group and 22.64% in the surgery alone group, with no statistically significant difference (P=0.380). In the nICT group, the objective response rate (ORR) was 84.38%, with 5 cases of complete response (CR)(15.63%), 22 cases of partial response (PR)(68.75%), 15 cases of pathological response rate (pCR)(46.88%), and 11 cases of major pathological reaponse (MPR) (34.38%). During nICT treatment, 12 cases (37.50%) experienced grade 3 treatment-related adverse events, no death induced by adverse events or immune related adverse events. Moreover, the symptoms of the patients were improved after nICT treatment.
CONCLUSIONS: Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC, with manageable treatment-related adverse events. It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.
【中文题目：新辅助免疫治疗联合化疗与手术治疗局部
晚期可切除非小细胞肺癌的短期疗效比较】 【中文摘要：背景与目的 肺癌是中国发生率和死亡率均排名第一的癌症，非小细胞肺癌（non-small cell lung cancer, NSCLC）占所有肺恶性肿瘤的80%-85%。目前，手术治疗仍是肺癌主要的治疗方式。近年来，免疫检查点抑制剂在NSCLC中的疗效已成为共识，新辅助免疫联合化疗（neoadjuvant immunochemotherapy, nICT）在早中期NSCLC中显示出来良好的疗效和安全性。然而，nICT治疗局部晚期NSCLC的相关研究较少。本研究旨在评估程序性死亡受体1（programmed cell death 1, PD-1）抑制剂联合含铂两药新辅助治疗治疗局部晚期可切除NSCLC的有效性和安全性。方法 纳入2021年1月至2024年4月于兰州大学第二医院胸外科就诊的85例确诊可切除IIIA、IIIB期患者，分为nICT组（n=32）和单纯手术组（n=53），比较两组患者的临床基线资料、围手术期相关指标及术后并发症，并评估nICT组的影像学缓解率、病理学缓解率、相关不良反应发生率、生活质量。结果 两组患者临床基线资料差异均无统计学意义（P>0.05）。nICT组选择开胸方式比单纯手术组发生率高（P=0.002），两组手术时间、术中出血量、清扫淋巴结个数、带管时间、术后住院时间及R0切除率的差异无统计学意义（P>0.05）。nICT组与单纯手术组术后总并发症发生率分别为31.25%和22.64%，差异无统计学意义（P=0.380）。nICT组中客观缓解率（objective response rate, ORR）为84.38%，完全缓解（complete response, CR）5例（15.63%），部分缓解（partial response, PR）22例（68.75%），病理性完全缓解（pathological complete response, pCR）15例（46.88%），主要病理缓解（major pathological reaponse, MPR）11例（34.38%）。nICT治疗期间，3级治疗相关不良反应共12例（37.50%），无不良反应或免疫相关不良反应导致患者死亡。而且，nICT治疗后患者相关症状有所改善。结论 nICT治疗局部晚期可切除NSCLC显示出良好的疗效，治疗相关不良事件可控，是局部晚期可切除NSCLC安全、可行的新辅助治疗模式。
】 【中文关键词：肺肿瘤；新辅助免疫化疗；PD-1抑制剂；客观缓解率；并发症】.

Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for advanced hepatocellular carcinoma (HCC) in China. Different efficacy between the two regimens combined with transvascular intervention for unresectable HCC (uHCC) remain unknown. We retrospectively analyzed uHCC patients treated in three centers by simultaneous combination of A+B or S+B with transarterial chemoembolization (TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (HAIC). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs) were compared. Totally 188 patients were included, with 92 and 96 administered A+B+TACE-HAIC (ABTH) and S+B+TACE-HAIC (SBTH), respectively. ORRs (62.0 vs. 70.8%, respectively; P = 0.257) and disease control rates (88.0 vs. 93.8%, P = 0.267) were similar between groups by the mRECIST criteria. ABTH showed no survival advantage over SBTH, with median PFS times of 11.7 months and 13.0 months, respectively (HR = 0.81, 95% CI, 0.52-1.26, P = 0.35) and similar OS times (HR = 1.19, 95% CI, 0.32-4.39, P = 0.8). No significant differences were observed in grade 3-4 TRAEs between groups. Either PD-L1 or PD-1 inhibitor plus bevacizumab combined with TACE-HAIC have similarly excellent therapeutic efficacy with manageable adverse events, representing promising treatment options for uHCC.