Background: The prognosis of small cell lung cancer (SCLC) patients is poor, and the standard first-line treatment for limited-stage small cell lung cancer (LS-SCLC) is still chemotherapy and thoracic radiotherapy. The primary objectives of our study were to confirm the superior efficacy of first-line immune checkpoint inhibitors (ICIs) plus etoposide and platinum (EP) for LS-SCLC and find crucial biomarkers. Methods: We analyzed LS-SCLC patients from three medical centers, employing propensity score matching for group comparability. Survival outcomes were estimated by Kaplan-Meier and Cox regression analyses. Additionally, we conducted univariate and multivariate analyses to investigate potential predictive factors. Results: Among 150 patients in our study, we successfully matched 41 pairs. The median overall survival (OS) was 29.5 months in the EP + ICIs group and 20.0 months in the EP group {hazard ratio (HR) =0.64 [95% confidence interval (CI): 0.41–1.02], P=0.059}. The median progression-free survival (PFS) was significantly extended in the EP + ICIs group (14.6 months), compared to the EP group (8.6 months) [HR =0.42 (95% CI: 0.28–0.63), P<0.001]. After matching, patients receiving chemo-immunotherapy had a median OS of 36.1 months, significantly surpassing those receiving chemotherapy alone (19.0 months) [HR =0.51 (95% CI: 0.28–0.93), P=0.02]. And the patients in the EP + ICIs group also had longer PFS after matching [HR =0.42 (95% CI: 0.25–0.71), P=0.001]. No significant difference in the objective response rate (ORR) and treatment-related adverse events (trAEs) between the two groups was found (ORR: EP: 81.0%, EP + ICIs: 90.0%, P=0.14; trAEs: EP: grade 1–2, 49.3%; grade 3–4, 42.5%; EP + ICIs: grade 1–2, 40.0%; grade 3–4, 49.1%, P=0.62). The multivariate analysis presented that the history of immunotherapy [EP + PD-1 inhibitors: HR =0.33 (95% CI: 0.17–0.62), P=0.001; EP + PD-L1 inhibitors: HR =0.18 (95% CI: 0.06–0.60), P=0.005] and baseline lung immune prognostic index (LIPI) [intermediate: HR =2.22 (95% CI: 1.20–4.13), P=0.01; poor: HR =2.03 (95% CI: 0.71–5.77), P=0.18] were independent prognostic factors for PFS among all LS-SCLC cases. However, no independent prognostic factor was identified for OS. Conclusions: Our real-world data showed promising clinical efficacy and tolerable safety of first-line programmed cell death protein 1 (PD-1) inhibitors or programmed cell death ligand 1 (PD-L1) inhibitors in cases with LS-SCLC. Additionally, LIPI may serve as a valuable prognostic factor.

Objective: To compare the prognostic differences between non-small cell lung cancer (NSCLC) patients with mild and severe checkpoint inhibitor-associated pneumonitis (CIP), and explore the causes of death and prognostic risk factors in NSCLC patients with severe CIP.Methods: A retrospective study of a cohort of 116 patients with unresectable stage III or IV NSCLC with any grade CIP from April 2016 to August 2022 were conducted. To analyze the clinical characteristics of patients with different CIP grades, patients were divided into mild CIP group (grade 1-2, n=49) and severe CIP group (grade 3-5, n=67) according to the grade of CIP. To explore the OS-related risk factors in the severe CIP group, the patients were divided into a good prognosis (GP) group (≥ median OS, n=30) and a poor prognosis (PP) group (< median OS, n=37) based on whether their overall survival (OS) were greater than median OS. Baseline clinical and laboratory data were collected for analysis.Results: The median OS of all NSCLC patients combined with CIP was 11.4 months (95%CI, 8.070–16.100), The median OS for mild CIP and severe CIP was 22.1 months and 4.4 months respectively (HR=3.076, 95%CI, 1.904-4.970, P<0.0001). The results showed that the most common cause of death among severe CIP patients in the PP group was CIP and the most common cause in the GP group was tumor. The univariate regression analysis showed that suspension of antitumor therapy was a risk factor for poor prognosis (OR=3.598, 95%CI, 1.307-9.905, p=0.013). The multivariate logistic regression analysis showed that suspension of anti-tumor therapy (OR=4.24, 95%CI, 1.067-16.915, p=0.040) and elevated KL-6 (OR=1.002, 95%CI, 1.001-1.002, p<0.001) were independent risk factors for poor prognosis.Conclusion: In conclusion, patients with severe CIP had a poor prognosis, especially those with elevated KL-6, and the main cause of death is immune checkpoint inhibitor-associated pneumonitis complicated with infection. In addition, anti-tumor therapy for severe CIP patients should be resumed in time and should not be delayed for too long.

Patients with breast cancer undergoing chemotherapy are susceptible to prolonged and severe neutropenia. Multiple biosimilars of long-acting granulocyte colony-stimulating factors (LA-G-CSFs) have been newly developed to prevent this disease. Nonetheless, which LA-G-CSF regimen has the optimal balance of efficacy and safety remains controversial. Moreover, there is a lack of evidence supporting clinical decisions on LA-G-CSF dose escalation in poor conditions. PubMed, Embase, Cochrane Library, Web of Science, and several Chinese databases were searched (December 2022) to collect randomized controlled trials (RCTs) about LA-G-CSFs preventing chemotherapy-induced neutropenia in breast cancer patients. No restrictions were imposed on language. A Bayesian network meta-analysis was performed. We assessed the incidence of severe neutropenia (SN) and febrile neutropenia (FN), the duration of SN (DSN), and the absolute neutrophil account recovery time (ANCrt) for efficacy, while the incidence of severe adverse events (SAE) was assessed for safety. The study was registered in PROSPERO (CRD42022361606). A total of 33 RCTs were included. Our network meta-analysis demonstrated that lipegfilgrastim 6 mg and eflapegrastim 13.2 mg outperformed other LA-G-CSFs with high efficacy rates and few safety concerns (SUCRA of lipegfilgrastim 6 mg: ANC rt 95.2%, FN 97.4%; eflapegrastim 13.2 mg: FN 87%, SN 89.3%). Additionally, 3.6 mg, 4.5 mg, 6 mg, and 13.2 mg dosages all performed significantly better than 1.8 mg in reducing the duration of SN (3.6 mg: DSN, SMD −0.68 [−1.13, −0.22; moderate]; 4.5 mg: −0.87 [−1.57, −0.17; low]; 6 mg: −0.89 [−1.49, −0.29; moderate]; 13.2 mg: −1.02 [1.63, −0.41; high]). Increasing the dosage from the guideline-recommended 6 mg to 13.2 mg can reduce both the duration and incidence of SN (SMD −0.13 [−0.24 to −0.03], RR 0.65 [0.43 to 0.96], respectively), with no significant difference in SAE. For patients with breast cancer, lipegfilgrastim 6 mg and eflapegrastim 13.2 mg might be the most effective regimen among LA-G-CSFs. Higher doses of LA-G-CSF may enhance efficacy without causing additional SAEs.

Immune checkpoint inhibitor-related pneumonitis (CIP) stands out as a particularly severe adverse event caused by immune checkpoint inhibitors, with a substantial real-world incidence ranging from 13 to 19%. While systemic corticosteroids represent the standard treatment for CIP, therapeutic options become limited in cases where patients do not respond to corticosteroid therapy. Such patients are classified as having steroid-resistant CIP, often associated with a poor prognosis. This case study provides insight into the symptoms, diagnostic process, and treatment approach for steroid-resistant CIP. Notably, successful management is demonstrated through the utilization of cyclosporine, highlighting its potential mechanisms of action in effectively treating steroid-resistant CIP. We present the case of a 53-year-old male with stage IV. A non-small cell lung cancer (NSCLC), who experienced elevated fever, cough, and dyspnea subsequent to immunotherapy treatment. Based on his medical history, clinical manifestations, and radiological findings, the patient was diagnosed with CIP. Initial administration of led to improvement, but during the subsequent tapering of corticosteroid therapy, a resurgence of CIP occurred, resulting in respiratory failure. Consequently, we arrived at the diagnosis of steroid-resistant CIP, prompting the implementation of a combination therapy with cyclosporine and corticosteroids to establish stable disease control. Upon systematic reduction of corticosteroid dosage, the patient maintained a favorable response with no recurrence. This marks the first instance of effectively managing steroid-resistant CIP through the combined use of cyclosporine and corticosteroids. Presently, cases of steroid-resistant CIP remain infrequent, necessitating vigilant and meticulous monitoring within clinical settings. Notably, there exists no distinct guideline specifying a singular agent for rescuing patients unresponsive to corticosteroid therapy. Therefore, cyclosporine emerges as a promising and efficacious treatment alternative for individuals unresponsive to corticosteroid intervention in the context of CIP.

The STK11 gene mutation is a common genetic alteration in non-small cell lung cancer (NSCLC) and is significantly associated with poor responses to current immunotherapy regimens. Despite its prevalence, there is currently no established standard for front-line treatment in this subtype of NSCLC, underscoring the increasing need for personalized therapeutic strategies. In this report, we present a case of a patient with STK11-mutant NSCLC who was treated with first-line cadonilimab (10mg/kg) in combination with pemetrexed (500mg/m^2) plus carboplatin (AUC=5), resulting in a notable extension of progression-free survival (PFS). This case highlights the potential efficacy and feasibility of combining immunotherapy with chemotherapy in patients with STK11-mutant NSCLC. Additionally, we provide a review of recent advancements in research related to STK11 mutations in lung cancer as reported in the literature.

Spontaneous remission (SR) of local recurrence after adjuvant immunotherapy has rarely been reported, and the underlying mechanism is poorly understood. Herein, we reported a patient with stage cT2aN2M0 squamous cell lung carcinoma who received neoadjuvant and adjuvant treatment with nivolumab plus chemotherapy. The patient experienced a late relapse in the subcarinal lymph node seven months after the last dosage of treatment but achieved SR in the next three months without additional antitumor therapy. The complete response lasted for eleven months and counting. Notably, high copies of pathogenic microorganisms were detected in the patient’s bronchoalveolar lavage fluid along with the recurrence but disappeared after SR. The patient also experienced a lymph node puncture-induced fever but had no other symptoms. A longitudinal analysis of infiltrated immune cells in the recurrent lymph node was performed by multiplex immunofluorescence and whole transcriptome sequencing, which revealed that CD8+ T cells were recruited during the initial relapse, specifically in the stromal area, then migrated into the tumor tissue, and continued to increase after elimination of tumor cells. Meanwhile, the initial recruitment of CD8+ T cells was coupled with a higher proportion of B cells, and the abundant neutrophil population was synchronous with the infiltration of CD8+ T cells into tumor cells. This is the first report on an Non-small cell lung cancer (NSCLC) patient with a late relapse after adjuvant immune checkpoint inhibitor (ICI) therapy who achieved SR. Our case highlights the complexity and plasticity of antitumor immunity and is expected to help find efficient strategies against the resistance of ICI treatment.