Programmed cell death-1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors are considered effective alternatives for the primary treatment of recurrent metastatic cancers. However, they can induce various adverse events affecting multiple organ systems, potentially diminishing patients' quality of life, and even leading to treatment interruptions. Adverse events related to PD-1/PD-L1 inhibitors differ from those associated with CTLA-4 inhibitors and are more commonly observed in the treatment of solid tumors. This study aimed to address the knowledge gap regarding adverse events related to PD-1/PD-L1 inhibitors. A visual bibliometric network was constructed using VOSviewer, CiteSpace, R software, and the Web of Science Core Collection (WoSCC) to quantitatively analyze this research field. Future research directions were also explored. The USA ranked first in publication count and total citations. Over time, publication types transitioned from case reports to clinical trials. Research on for nivolumab was the most prevalent. The spectrum of cancers treated by PD-1/PD-L1 inhibitors expanded beyond melanoma and lung cancer to include renal cell carcinoma, esophageal cancer, and others. Common adverse events included pneumonitis, myasthenia gravis, and vitiligo. There was a significant increase in multi-phase clinical trials and studies related to biomarkers. This study offers valuable insights for potential collaborators and institutions, highlighting trends in the study of adverse events related to PD-1/PD-L1 inhibitors. The management of these adverse events has become more refined and standardized. Biomarker research and multi-phase clinical trials are likely to be key areas of focus in future studies.

The utilization of immune-checkpoint inhibitors (ICIs) in cancer immunotherapy frequently leads to the occurrence of immune-related adverse events (irAEs), making it generally not recommended for patients with preexisting autoimmune diseases. Hence, we conducted a meta-analysis on safety and efficacy of ICIs in cancer patients with preexisting autoimmune diseases to provide further insights. PubMed, EMBASE, and Cochrane Library were systematically searched until December 20, 2024. The main summary measures used were pooled rate and risk ratio (RR) with 95% confidential interval (CI), which were analyzed using R statistic software. A total of 52 articles were included in the study. When cancer patients with preexisting autoimmune diseases received ICIs treatment, the overall incidence was 0.610 (95% CI: 0.531-0.686) for any grade irAEs, 0.295 (95% CI: 0.248-0.343) for flares, 0.325 (95% CI: 0.258-0.396) for de novo irAEs, 0.238 (95% CI: 0.174-0.309) for grade ≥3 irAEs, and 0.143 (95% CI: 0.109-0.180) for discontinuation due to immunotoxicity. Compared with those without autoimmune diseases, cancer patients with autoimmune diseases experienced a higher risk of any-grade irAEs (RR: 1.23, 95% CI: 1.12-1.35) and discontinuation due to immunotoxicity (1.40, 95% CI: 1.11-1.78). However, no statistically significant differences were observed in the incidence of grade ≥3 irAEs, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between the two groups. During ICIs treatment, irAEs are common among cancer patients with autoimmune diseases, but severe irAEs is relatively low. ICIs are effective in this population, but should be strictly monitored when used to avoid immunotoxicity.

Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide.

IMforte was a randomised, open-label, phase 3 trial done at 96 hospitals and medical centres in 13 countries (Belgium, Germany, Greece, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the UK, and the USA). Eligible patients were aged 18 years or older with treatment-naive ES-SCLC. Patients received four 21-day cycles of induction treatment (atezolizumab, carboplatin, and etoposide). After completing induction treatment, eligible patients without disease progression were randomly assigned (1:1) using permuted blocks (Interactive Voice/Web Response System) to receive maintenance treatment intravenously every 3 weeks with lurbinectedin (3·2 mg/m2; with granulocyte colony-stimulating factor prophylaxis) plus atezolizumab (1200 mg) or atezolizumab (1200 mg). The two primary endpoints were independent review facility-assessed (IRF) progression-free survival and overall survival, measured from randomisation into the maintenance phase. Efficacy endpoints were assessed in the full analysis set, which included all patients who were randomly assigned to maintenance phase treatment, regardless of whether they received their assigned study treatment. Safety was assessed in all patients who received at least one dose of lurbinectedin or atezolizumab, and was analysed according to the treatment received. This study is registered with ClinicalTrials.gov, NCT05091567, and is closed for recruitment.

Between Nov 17, 2021, and Jan 11, 2024, 895 patients were screened for enrolment, of whom 660 (74%) were enrolled into the induction phase. Between May 24, 2022, and April 30, 2024, 483 (73%) of 660 patients entered the maintenance phase and were randomly assigned to lurbinectedin plus atezolizumab (n=242) or atezolizumab (n=241). At the data cutoff (July 29, 2024), IRF progression-free survival was longer in the lurbinectedin plus atezolizumab group than the atezolizumab group (stratified hazard ratio [HR] 0·54 [95% CI 0·43-0·67]; p<0·0001), as was overall survival (stratified HR 0·73 [0·57-0·95]; p=0·017). 92 (38%) of 242 patients in the lurbinectedin plus atezolizumab group and 53 (22%) of 240 patients in the atezolizumab group had grade 3-4 adverse events. The most common grade 3-4 events in the lurbinectedin plus atezolizumab group were anaemia (20 [8%] of 242 patients), decreased neutrophil count (18 [7%] patients), and decreased platelet count (18 [7%] patients) and the most common events in the atezolizumab group were hyponatremia (five [2%] of 240 patients), dyspnoea (four [2%] patients), and pneumonia (four [2%] patients). Grade 5 adverse events occurred in 12 (5%) of 242 patients in the lurbinectedin plus atezolizumab group and six (3%) of 240 patients in the atezolizumab group. The incidence of myelosuppressive toxicities (eg, neutropenia and leukopenia) was higher in the lurbinectedin plus atezolizumab group than the atezolizumab group.

IRF progression-free survival and overall survival were longer in the lurbinectedin plus atezolizumab group than the atezolizumab group for patients with ES-SCLC, albeit with a higher incidence of adverse events. Lurbinectedin plus atezolizumab represents a novel therapeutic option for first-line maintenance treatment in this setting.

F Hoffmann-La Roche and Jazz Pharmaceuticals.

This study aims to evaluate the efficacy and safety of anlotinib combined with immune checkpoint inhibitors (ICIs) in patients with previously immunotherapy-treated extensive-stage small cell lung cancer (ES-SCLC).

This retrospective study screened ES-SCLC patients who experienced failure after prior ICIs-based treatment and received anlotinib combined with ICIs therapy clinically. Anlotinib was administered at a standard dosage, ICIs regimens included PD-1 inhibitors (Tislelizumab, 200 mg; serplulimab, 4.5 mg/kg) and PD-L1 inhibitors. Efficacy and safety data during treatment were retrospectively collected, and patients were followed up regularly to obtain long-term survival data. Subgroup analysis was conducted to identify the differences in treatment outcomes in various baseline characteristics.

Of the 68 ES-SCLC patients included, no complete response, 22 patients achieved partial response, 28 had stable disease, 14 experienced disease progression and 4 patients were not available for efficacy. Objective response rate (ORR) was 32.4% (95% CI: 21.5-44.8%), and disease control rate (DCR) was 73.5% (95% CI: 61.4-83.5%). The median progression-free survival (PFS) was 5.6 months (95% CI: 3.87-7.33), the median duration of response (DoR) was 6.8 months (95% CI: 0.80-12.83). At the data cutoff date, the median follow-up duration was 12.5 months (range: 1.1-31.5 months), yielding a median overall survival (OS) of 13.2 months (95% CI: 7.09-19.31). Subgroup analysis highlighted that patients who were previously intolerant to immunotherapy had a longer OS (median OS: 15.5 vs 10.9 months, P = 0.031). Safety analysis showed that 61 patients (89.7%) experienced treatment-related adverse events (TRAEs) of varying severity with 37 patients (54.4%) developing grade 3 or higher. The most common TRAEs included fatigue, nausea and vomiting, hypertension, hematologic toxicity, and liver function abnormalities.

Anlotinib combined with ICIs demonstrated that immunotherapy rechallenge in previously ICIs-treated ES-SCLC was feasible and of clinical significance preliminarily. However, larger-scale clinical studies were required to validate these findings subsequently.

This real-world study aimed to investigate the efficacy of early radiotherapy (RT) in ES-SCLC patients treated with first-line chemo-immunotherapy.

ES-SCLC patients were enrolled from August 2018 to October 2023. Patients who received early radiotherapy before disease progression were defined as Early RT group, while the others, named Salvage and Non-RT (S&N RT) group. Propensity score matching (PSM) with a 1:1 ratio was performed to balance the baseline characteristics.

In this study, 375 patients with ES-SCLC treated with first-line chemo-immunotherapy were enrolled. The median PFS was 11.4 months of the Early RT group compared to 6.1 months of the S&N RT group (HR = 0.59, 95%CI 0.45-0.77; p < 0.001). The median OS was 23.8 months of the Early RT group versus 18.0 months of the S&N RT group (HR = 0.50, 95%CI 0.34-0.73; p = 0.004). The survival benefit persisted in the PSM cohort. Furthermore, survival was significantly improved in Early RT group compared to Salvage RT group (p = 0.028), while Salvage RT group had a similar survival with Non-RT group (p = 0.868). The risk of adverse events was tolerable. The multivariate analysis also demonstrated that early radiotherapy was an independently positive predictor for PFS and OS.

Administering early radiotherapy significantly improved both PFS and OS in patients with ES-SCLC treated with first-line chemo-immunotherapy with tolerable adverse events, while salvage radiotherapy did not improve survival. This finding warrants further validation through prospective randomized studies.

Deciphering interactions between tumor micro- and systemic immune macroenvironments is essential for developing more effective cancer diagnosis and therapeutic strategies. Here, we established a gel-liquid interface (GLI) co-culture model of lung cancer organoids (LCOs) and paired peripheral-blood mononuclear cells (PBMCs), featuring enhanced interactions between immune cells and tumor organoids for optimized simulation of in vivo systemic anti-tumor immunity. By constructing a cohort of lung cancer patients, we demonstrated that the responses of GLI models under αPD1 treatment reflected the immunotherapy outcomes of the corresponding patients precisely. Furthermore, we dissected the various tumor immune processes mediated by PBMC-derived T cells within GLI models through functional multi-omics analyses, along with the characterization of circulating tumor-reactive T cells (GNLY+CD44+CD9+) with effector memory-like phenotypes as a potential indicator of immunotherapy efficacy. Our findings indicate that the GLI co-culture model can be used to develop diagnostic strategies for precision immunotherapies, as well as understanding the underlying mechanisms.

Surrogate endpoints, such as progression-free survival (PFS) and objective response rate (ORR), are increasingly used in oncology trials to expedite drug development and decision making. This paper evaluates the effectiveness of these surrogate endpoints by analyzing their correlations with overall survival (OS) across different cancer types, treatments, and therapy lines at both the patient and trial levels using an integrated dataset from Bristol Myers Squibb. At the patient level, correlation between OS and PFS was consistently stronger than those between OS and best overall response (BOR), suggesting that PFS may serve as a more reliable surrogate for OS. Melanoma patients exhibited the highest correlation between OS and BOR, and immune-oncology (IO) therapy patients showed stronger correlations than those treated with chemotherapy. First-line therapy patients demonstrated stronger correlations between BOR, PFS, and OS compared with second-line or third-line patients. At the trial level, the correlation between PFS hazard ratio (HR) and difference in ORR (∆ORR) was stronger than that between other endpoints. Melanoma studies exhibited strong correlations with significant P-values. IO therapy studies exhibited more consistent correlations.

This study aimed to investigate the impact of oligometastasis and the M descriptor on survival in small cell lung cancer (SCLC).

This multicenter, retrospective study included patients with newly diagnosed extensive-stage SCLC(ES-SCLC) from 2010 to 2020. Subgroups: Group 1: single metastasis in a single organ, Group 2: 2-5 metastases in a single organ, Group 3: 6 or more metastases in a single organ, and Group 4: metastases in two or more organs. This classification was based on the 9th Staging-M descriptor. Three-year progression-free survival (PFS) and overall survival (OS) analyses were conducted.

The mean age of the 439 patients was 62 ± 10 years, and 89.5% of them were male. The mean PFS for Groups 1, 2, 3, 4 was 10.7 months (95% CI 8.9-12.5), 7.5 months (95% CI 5.6-9.4), 4.3 months (95% CI 2.9-5.7), and 5.4 months (95% CI 4.7-6.1), respectively. PFS in Group 2 was significantly higher. The mean OS for Groups 1, 2, 3, 4 was 13.3 months (95% CI 11.2-15.3), 9.5 months (95% CI 7.1-11.9), 7.1 months (95% CI 4.5-9.7), and 6.9 months (95% CI 6.0-7.9), respectively. OS in Group 1 was significantly higher. OS and PFS in the M1b group were significantly higher than in the M1c1 and M1c2 groups (p < 0.05) with no statistical difference between the M1c1 and M1c2 groups.

There is no significant difference in survival between the M1c1 and M1c2 groups. In ES-SCLC, the number of metastases may be a more predictive factor for prognosis than the number of metastatic organs.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with ~7% 5-year overall survival reflecting early metastasis and rapid acquired chemoresistance. Immunotherapy briefly extends overall survival in ~15% cases, yet predictive biomarkers are lacking. Targeted therapies are beginning to show promise, with a recently approved delta-like ligand 3 (DLL3)-targeted therapy impacting the treatment landscape. The increased availability of patient-faithful models, accumulating human tumour biobanks and numerous comprehensive molecular profiling studies have collectively facilitated the mapping and understanding of substantial intertumoural and intratumoural heterogeneity. Beyond the almost ubiquitous loss of wild-type p53 and RB1, SCLC is characterized by heterogeneously mis-regulated expression of MYC family members, yes-associated protein 1 (YAP1), NOTCH pathway signalling, anti-apoptotic BCL2 and epigenetic regulators. Molecular subtypes are based on the neurogenic transcription factors achaete-scute homologue 1 (ASCL1) and neurogenic differentiation factor 1 (NEUROD1), the rarer non-neuroendocrine transcription factor POU class 2 homeobox 3 (POU2F3), and immune- and inflammation-related signatures. Furthermore, SCLC shows phenotypic plasticity, including neuroendocrine-to-non-neuroendocrine transition driven by NOTCH signalling, which is associated with disease progression, chemoresistance and immune modulation and, in mouse models, with metastasis. Although these features pose substantial challenges, understanding the molecular vulnerabilities of transcription factor subtypes, the functional relevance of plasticity and cell cooperation offer opportunities for personalized therapies informed by liquid and tissue biomarkers.

Small cell lung cancer (SCLC) remains a challenge prognostically. A clinically silent early stage and predilection for early metastasis leads to over half of patients presenting with metastatic disease at the time of diagnosis. Akin to many other cancers, once SCLC metastasizes, current therapies begin to lose their effectiveness. The future of SCLC rests in innovative treatments aimed at improving patient outcomes. Chemotherapy and radiation remain the backbone treatment for SCLC. Most patients diagnosed with SCLC begin treatment with combination chemotherapy consisting of a platinum analog and topoisomerase inhibitor with or without concurrent radiation. Disease progression or recurrence warrants new treatment approaches. New chemotherapy combinations and advances in radiation precision offer patients novel approaches using the same backbone of treatment used in many other cancers. The introduction of newer therapeutic approaches, such as immune checkpoint inhibitors, small molecule targeted therapies, bispecific antibodies, and antibody-drug conjugates offer a bright future for patients with SCLC who fail first-line therapy. This review will focus on advancing treatment paradigms for SCLC in the era of precision medicine. Such a study might be helpful for pulmonologists and oncologists to manage precisely patients with SCLC.

Extensive-stage small-cell lung cancer (ES-SCLC) poses a formidable challenge due to its aggressive nature and poor prognosis. While immune checkpoint inhibitors have shown promise as part of first-line therapy, their cost-effectiveness and survival benefits in the Chinese healthcare system are not well understood. This study evaluates the cost-effectiveness of first-line tislelizumab combined with chemotherapy versus chemotherapy alone for ES-SCLC.

We conducted a cost-effectiveness analysis using a partitioned survival mode (PSM) to compare tislelizumab plus chemotherapy versus chemotherapy alone for the first-line treatment of ES-SCLC. The model integrated survival estimates from the RATIONALE-312 Phase III clinical trial, direct medical costs, and quality-adjusted life year (QALY) sourced from the literature. We calculated 10-year cost per QALY gained from Chinese healthcare system perspective. The analysis of cost-effectiveness was benchmarked against a willingness-to-pay threshold three times of GDP per capita in China. Sensitivity analyses were conducted to evaluate parametric uncertainty and model robustness.

Compared to the chemotherapy alone group, the tislelizumab plus chemotherapy group resulted in an incremental cost-effectiveness ratio (ICER) of US$31,072.79 per quality-adjusted life-year (QALY), which is below the threshold of US$37,765 per QALY. Sensitivity analyses indicated that the utility value of progression-free survival (PFS) is a principal determinant of the ICER, with the ratio fluctuating between $27,246 and $36,417 per QALY, well below the willingness-to-pay threshold. In scenario analyses, tislelizumab plus chemotherapy resulted in an ICER of US$ 38,665.59/QALY with PET-CT imaging (exceeding the $37,765/QALY threshold) but was cost-effective at US$ 30,076.37/QALY when imported topotecan was used as second-line treatment.

Tislelizumab plus chemotherapy demonstrates cost-effectiveness in the first-line treatment of ES-SCLC in China. This study provides preliminary evidence for the economic value of tislelizumab in the treatment of ES-SCLC, supporting its consideration as a first-line therapeutic option.

Small-cell lung cancer (SCLC) has limited therapeutic options beyond first-line treatment, and the efficacy of PD-1/PD-L1-based immunotherapy in this setting remains uncertain. This study evaluates the efficacy and safety of serplulimab-based immunochemotherapy as a second- or later-line treatment for SCLC.

This retrospective, real-world study included 39 SCLC patients treated with post-initial serplulimab-based immunochemotherapy at Shanxi Provincial Cancer Hospital between May 2022 and November 2023. Primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Cox analyses were conducted to explore factors associated with survival outcomes.

The median follow-up duration was 13.7 months. The OS was 12.00 months (95% CI: 6.87-not reached), and the median PFS was 4.07 months (95% CI: 3.07-7.17), with an objective response rate of 20.51%. Patients who underwent immunotherapy re-challenge showed numerically higher median OS (12.77 vs. 9.17 months) and PFS (5.93 vs. 3.87 months) than those without prior immunotherapy. Patients with an objective response to front-line therapy exhibited a trend toward improved median OS (not reached vs. 6.47 months) and PFS (5.93 vs. 3.17 months). Cox analysis identified ECOG PS of 2, elevated LDH, ProGrp, and NSE, and liver metastasis were associated with worse OS. The most common adverse events were thrombocytopenia, elevated ALT, and hypothyroidism, with a manageable safety profile.

Second- or later-line serplulimab-based immunochemotherapy shows promising antitumor activity and survival benefits for SCLC, regardless of prior immunotherapy exposure. Although limited by sample size and retrospective design, these findings highlight the potential of immunotherapy combinations beyond first-line therapy.

Neuroblastoma (NB) is the most prevalent extracranial childhood tumor and the third leading cause of death from cancer in children. Despite having a high overall survival rate for low- and intermediate-risk patients, survival rates for high-risk cases remain unsatisfactory. The current standard treatment for high-risk NB involves surgery, chemotherapy, radiotherapy, autologous stem cell transplantation, immunotherapy with anti-ganglioside GD2, and differentiation therapy with isotretinoin. Besides not being enough to achieve a high survival rate in high-risk patients, these treatments are associated with significant side effects. With next-generation sequencing technologies, a better understanding of the genetic and epigenetic landscapes of NB has been achieved. This has led to the study of novel treatments to improve the overall survival rate of high-risk NB and reduce the toxicity of conventional treatments. Current research is focusing on the development of targeted drugs for genetic and epigenetic alterations, and protein degraders. Moreover, immunotherapy to enhance anticancer immune responses and by using cell-engineering techniques with chimeric antigen receptor (CAR) T and NK cells are being explored to target NB cells. Here, we review promising novel treatment strategies for NB, which target genetics, epigenetics, the tumor microenvironment, and the immune landscape, highlighting preclinical studies and ongoing clinical trials.

Small-cell lung cancer (SCLC) transformation is one of the major mechanisms of resistance to Epidermal Growth Factor Receptor tyrosine kinase inhibitors (EGFR-TKIs). Chemotherapy is typically the recommended treatment for transformed SCLC (T-SCLC), similar to primary SCLC. However, the benefits of chemotherapy alone are minimal. Prior research highlights differences between the biological traits of T-SCLC and primary SCLC or EGFR-mutated lung adenocarcinoma (LUAD). This study aims to elucidate the molecular characteristics of T-SCLC and identify potential treatment modalities.

We retrospectively collected tissue samples from LUAD, T-SCLC post-EGFR-TKI resistance, and primary SCLC. Genomics, transcriptomics, and proteomics were performed to clarify the differences between T-SCLC, LUAD, and primary SCLC. Hierarchical clustering analysis was then used to categorize the molecular subtype of T-SCLC, followed by a survival analysis based on these subtypes.

A study involving 61 patients investigated differences between LUAD, SCLC, and primary SCLC. RNA sequencing revealed distinct gene expression variations, particularly up-regulation in PPM1E, INSM1, and KCNC1 genes in T-SCLC. Pathway analysis linked T-SCLC to the cell cycle and neural differentiation. By conducting Hierarchical clustering analysis on RNA-seq data, the entire population can be categorized into two distinct groups. While certain T-SCLC showed similarities and differences compared to SCLC, with subtypes: LUAD-like and Non-LUAD-like. Notably, the LUAD-like subtype had significantly higher NKX2-1 expression (mean 371.8 vs. 41.8, P < 0.0001). T-SCLC treatment approaches were categorized into matched and unmatched groups, delineated by the alignment of specific therapies with corresponding pathologies. The matched group (13 cases) exhibited a significantly prolonged median progression-free survival compared to the unmatched group (10 cases) (5.4 months vs. 3.6 months, P = 0.02).

T-SCLC exhibits marked molecular distinctiveness, setting it apart not only from LUAD but also from classical SCLC. This distinction extends to its classification into two discernible molecular subtypes: LUAD-like and Non-LUAD-like. Customizing therapeutic protocols to align with these specific subtypes have the potential to identify the most appropriate treatment for T-SCLC.

Small cell lung cancer is an aggressive malignancy with limited treatment options and poor prognosis, particularly at extensive stage. While first-line platinum-etoposide chemotherapy combined with anti-PD-L1 therapy improves survival, most patients relapse, highlighting the need for novel therapies.

B7-Homolog3 (B7-H3), an immune checkpoint molecule overexpressed in SCLC, has emerged as a promising therapeutic target. Ifinatamab deruxtecan (I-DXd) is an antibody-drug conjugate targeting B7-H3, delivering a topoisomerase I inhibitor. Early clinical trials (IDeate-PanTumor01 and IDeate-Lung01) have demonstrated encouraging results in pretreated ES-SCLC. In the 12 mg/kg cohort of IDeate-Lung01, I-DXd achieved an objective response rate of 54.8%, median progression-free survival of 5.5 months, and median overall survival of 11.8 months. Notably, it showed intracranial activity with a central nervous system-confirmed response rate of 37.8%.

I-DXd is currently being evaluated in the phase III IDeate-Lung02 trial. Its promising efficacy, manageable safety profile, and potential in combination strategies position it as a key candidate for future SCLC treatment.

Platinum-based first-line chemotherapy for small lung cancers has been a mainstream therapy for the past several decades. However, its efficacy has been suboptimal, and the research is now focused on improving the treatment and prognosis of competitive nutrition and multidrug combination techniques. Small cell lung cancer (SCLC) is not only affected by smoking, age, sex and other external factors, but also the tumor micro-environment and the nutritional status of patients themselves are of great significance for the prevention and treatment of SCLC, a malignant tumor. According to past research, malnutrition is related to the intolerance to immunotherapy, decline in quality of life, psychological disturbances, and low survival rates and prognosis. Numerous studies have shown that a low Prognostic Nutritional Index (PNI) serves as an independent prognostic factor linked to reduced overall survival across various cancer types. Additionally, PNI has been associated with disease-free survival and progression-free survival in certain cancers, such as lung cancer (LC). Recent research has indicated that the PNI can serve as an independent predictor of both long-term outcomes and short-term complications in SCLC patients. However, a systematic consensus on this matter has yet to be established. This paper focuses on the role and influence of PNI in the immunotherapy of SCLC, and proposes the possibility of dietary therapy for SCLC patients under the guidance of PNI. Finally, the authors pointed out that PNI will become a new strategy for comprehensive immunotherapy of SCLC.

This study evaluated the efficacy and safety of thoracic radiotherapy (TRT) after first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC), focusing on the impact of different TRT timing strategies (consolidative vs. salvage) on survival. A total of 54 ES-SCLC patients treated between January 2019 and July 2022 were retrospectively analyzed. Patients receiving consolidative TRT (cTRT) within 3 months after first-line treatment completion were compared to those receiving salvage TRT (sTRT) following disease progression. Primary endpoints included overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS); safety was a secondary endpoint. The cTRT group (n=41) showed significantly longer median OS (26.6 vs. 14.8 months, P=0.048), PFS (12.9 vs. 3.5 months, P< 0.0001), and DMFS (10.7 vs. 3.4 months, P= 0.0044) than the sTRT group (n=13). Multivariate analysis identified cTRT as an independent favorable prognostic factor. No significant differences in OS or LRFS were found between high-dose (≥50 Gy) and low-dose (<50 Gy) TRT. Hematologic and respiratory toxicities were the most common adverse events, with acceptable tolerability. In conclusion, consolidative TRT after chemoimmunotherapy significantly improves survival outcomes in ES-SCLC patients, and low-dose TRT may be a suitable option.

While chemo-immunotherapy has been established as the frontline therapeutic regimen for extensive-stage small cell lung cancer (ES-SCLC), durable responses persist predominantly in a minor population of patients. This underscores critical need to elucidate underlying local tumor microenvironment and systematic immune profiles for biomarker discovery. In this phase II trial (ChiCTR2000038354), the efficacy, safety, and immune-genomic signatures of sintilimab (anti-PD-1 antibody) synergized with chemotherapy as first-line regimen for ES-SCLC were evaluated. The regimen demonstrated a median progression-free survival (PFS) of 6.9 months and median overall survival of 17.1 months, accompanied by a 12-month PFS rate of 16.9%, fulfilling the primary endpoint. Manageable grade 3 or 4 treatment-related adverse events developed in 27.3% (12/44) of patients. The exploratory study indicated a higher infiltration of CD4+/CD8+ CXCR5+ T follicle helper cells, CD8+CD103+ tissue-resident memory T cells, and B cells in tumor tissue, associated with better response and prognosis. The study also indicated the presence of tumor macrophages (CD68+CD163+CSF1R+SIGLEC5+) associated with immunotherapy resistance. Higher levels of monocyte-dendritic cells in pre-treatment peripheral blood mononuclear cells were found in durable clinical benefit group. Also, higher CD83, CD244, IL-12, and CD70, which are hallmarks of dendritic cells and activated T cells, were discovered by plasma proteomics to be connected with enhanced outcomes, while chemoattractant of macrophage, CSF-1, CCL3, CCL4, and IL-8, were found to predict a worse prognosis. Furthermore, a multimodal model was constructed and validated for stratifying ES-SCLC into high or low risk to predict the immunotherapy efficacy. This study sheds light on harnessing local and systematic immune profiles to better stratify patients with ES-SCLC for immunotherapy and putative combinational treatment.

Chemoimmunotherapy has emerged as the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), improving survival outcomes. However, the role of prophylactic cranial irradiation (PCI) in the context of chemoimmunotherapy remains undefined.

This study aimed to evaluate the impact of PCI on overall survival (OS) in patients with ES-SCLC after chemoimmunotherapy administration.

Retrospective study.

This retrospective analysis included 261 patients with ES-SCLC treated with first-line chemoimmunotherapy between January 2019 and December 2023. All patients underwent MRI scans to confirm the absence of brain metastases. After 1:2 propensity score matching (PSM), 46 and 81 patients were assigned to the PCI and observation groups, respectively. The primary endpoint was OS, with additional exploration of progression-free survival (PFS), the cumulative incidence of intracranial metastases, and intracranial progression-free survival (iPFS).

After PSM, the two groups were well-balanced in baseline characteristics. Survival analysis showed a median OS of 19.9 months (95% confidence interval (CI): 11.8-28.0) in the PCI group and 15.6 months (12.3-18.9) in the observation group, without a significant difference (hazard ratio (HR) = 0.763 (95% CI: 0.484-1.206), log-rank p = 0.265). PCI significantly reduced the risk of brain metastasis (Fine-Gray p = 0.002), with 1-year cumulative incidence rates of 13.8% (3.4%-24.2%) in the PCI group and 53.4% (41.3%-65.6%) in the observation group. Subgroup analysis showed that for ES-SCLC patients achieving a partial response to initial chemoimmunotherapy, the PCI group had longer median OS (25.7 months (95% CI: 15.4-36.1) vs 19.4 months (15.4-23.4); HR = 0.502 (0.284-0.886); log-rank p = 0.021).

PCI did not improve OS in ES-SCLC patients receiving first-line chemoimmunotherapy, while it may confer a survival benefit for patients who achieve remission following chemoimmunotherapy. In addition, PCI significantly reduced the incidence of brain metastases. These findings warrant further randomized studies for verification.

Anti-PD-L1 immunotherapy is recommended as standard of care for patients with extensive stage small cell lung cancer (ES-SCLC); however, there are no reliable biomarkers guiding patient selection and the survival benefit of PD-L1 inhibitors in the overall population is limited. In this study, we retrospectively analyzed a total number of 61 cases of ES-SCLC who underwent anti-PD-L1 immunotherapy. Patient demographic characteristics and laboratory findings were processed for univariate and multivariate analysis. Subgrouping of SCLC was performed on IHC platform using antibodies against ASCL1, NEUROD1 and POU2F3. The tumor microenvironment (TME) of ES-SCLC was evaluated by CD8 + T cell infiltration, granzyme B production and PD-L1 expression. We found limited efficacy of defined variable factors conferring therapeutic outcomes of anti-PD-L1 immunotherapy in patients with ES-SCLC. Intriguingly, there was a profound difference in TME and response to anti-PD-L1 immunotherapy when classifying SCLC into A/N/P/I subgroups. Although accounted for a small proportion of SCLC, the SCLC-P and SCLC-I subtypes manifested as T cell-enriched "hot" tumor and elicited more favorable response to immunotherapy, whereas the SCLC-A and SCLC-N subgroups were T cell-absent "cold" tumor. There was also a significant difference in progression free survival and overall survival across these subsets. Moreover, we found the SCLC-P and SCLC-I tumors revealed features of low neuroendocrine (NE) differentiation and showed clinicopathologic features overlapping with the SCLC non-NE lineage. These findings may aid clinicians to select ES-SCLC patients who were more likely to gain higher response rate and longer survival to anti-PD-L1 immunotherapy. Revisiting SCLC according to A/N/P/I subtyping and NE/non-NE differentiation is a reliable approach to guide therapeutic strategy in patients with ES-SCLC.

With the inspiring results of the PACIFIC trial in non-small-cell lung cancer (NSCLC), and the CAPIAN and IMpower133 trials in extensive-stage small-cell lung cancer (SCLC), immunotherapy has increasingly gained attention. Serplulimab, a PD-1 inhibitor, showed great antitumour activity in the ASTRUM-005 trial and has been recommended as first-line therapy in extensive-stage SCLC. Whether serplulimab following hypofractionation radiotherapy and chemotherapy could bring better outcomes in limited-stage SCLC remains to be answered.

We designed a prospective multicentre single-arm phase II clinical trial to evaluate both the efficacy and safety of chemoradiotherapy and consolidation by serplulimab in limited-stage SCLC. Eligible patients will receive standard chemotherapy for four cycles and concurrent thoracic radiotherapy with a total dose of 45 Gy in 3 weeks and a 3 Gy dose per fraction. Prophylactic cranial irradiation is recommended for responding patients. Serplulimab will be delivered afterwards every 3 weeks for up to 1 year. Based on sample size estimation, 55 patients will be enrolled in total.

Ethics approval was obtained from the Independent Ethics Committee of National Cancer Centre/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (22/236-3438).

NCT05443646.

The prevalence of Programmed death ligand 1 (PD-L1) expression in the population of NSCLC patients and blocking the PD1/PD-L1 pathway by inhibiting the PD-1 receptor on immune cells or the PD-L1 ligand on tumour and/or immune cells can inhibit tumour growth. EFBALite algorithm that enables efficient and cost-effective selection of aptamers, expediting the process. Here, we present the development, computational validation, and in vitro analysis of NSCLC of DNA aptamers targeting PD-L1. The Gibbs free energy of two anti-PD-L1 aptamers, Apta35 and Apta90 with -3.06 and - 2.4 kcal/mol respectively. The docking score for Apta35 was -272.3 and 1171.765 for HDOCK and ZDOCK respectively. Further, the Apta35 was taken for the in vitro studies as it was more stable and incubated with NCI-H460. Initially, we confirmed the binding of the TAMRA-labelled Apta35 to the NCI-H460 cell surface through microscopic imaging and further confirmed through FACS analysis. Further experimental results showed that the Apta35 treated along with the act-T cells group reduced the percentage of viability (28 ± 3.5), increased toxicity, and reduced count of NCI-H460 cells when compared with the cells treated only with the act-T cells concerning the treatment to 50 nM concentration. In summary, targeting PD-L1 with a specific aptamer provides an innovative strategy for targeting NSCLC. Apta35 aptamer showed no significant toxicity in the BALB/c nude mice while it was injected every 2 days for a total of 12 days of treatment.

Chemo-immunotherapy (CT-IO) has improved median overall survival (mOS) for patients with extensive-stage small cell lung cancer (ES-SCLC), but its association with immune-related adverse events (irAEs) remains unclear. While irAEs are often linked to better outcomes in other cancers, their prognostic value in ES-SCLC is not well understood.

We conducted a retrospective analysis of 399 consecutive ES-SCLC patients treated with first-line CT-IO between January 2020 and September 2024 across five European centres. Demographic and clinical data were collected. The impact of irAEs on progression-free survival (PFS) and overall survival (OS) was assessed using time-dependent Cox regression.

The median follow-up was 15.0 months. The overall response rate was 80.3 %, with a median PFS of 6.0 months (95 % CI 5.7-6.3) and mOS of 10.4 months (95 % CI 9.2-11.6). IrAEs occurred in 30.6 % of patients, most commonly affecting the skin (11.0 %). The median time to onset of irAEs was 171 days. Patients with irAEs had significantly longer mPFS (10.8 vs. 5.3 months, p < 0.001) and mOS (18.8 vs. 7.6 months, p < 0.001) compared to those without. No significant difference was found between patients with grade ≥ 3 (n = 46) and < 3 irAEs (n = 76). Multivariate analysis confirmed that irAEs were associated with improved OS (HR 0.64; 95 % CI 0.51-0.80, p < 0.001) and showed a trend towards longer PFS (p = 0.028).

This is the largest retrospective study to demonstrate that irAEs are associated with improved clinical outcomes in ES-SCLC pts receiving 1 L CT-IO.

Lung cancer, a malignant neoplasm that is globally prevalent and characterized by high incidence and mortality rates, has seen the rise of immune checkpoint inhibitors (ICIs) as a crucial systemic treatment. However, a subset of patients exhibits suboptimal responses to ICIs. Recently, studies revealed the role of vitamin D in inflammation modulation, cell differentiation, and cancer prevention. Vitamin D precisely modulates immune responses and inflammatory states within the tumor microenvironment (TME) by targeting both innate and adaptive immunity. These effects may reduce immune tolerance to ICIs and synergistically enhance their therapeutic efficacy. Here, we review vitamin D metabolism in lung cancer patients, as well as its anti-tumor mechanisms, immune regulation, and the significant promise of vitamin D in lung cancer immunotherapy and adjuvant therapeutic strategies. Further research is imperative to surmount these challenges and fully realize vitamin D's potential in improving lung cancer immunotherapy outcomes.

Patients with small cell lung cancer (SCLC) generally have a poor prognosis, with an exceptionally high proliferative rate and a strong propensity for early metastasis, indicating the urgent need for novel therapies. The development of chimeric antigen receptor (CAR)s targeting solid tumors is limited owing to the lack of target antigens and low efficacy. In this study, we aimed to discover new targets for SCLC CAR-T therapy and develop CAR-T-based combinational treatment against SCLC in preclinical models.

The in vitro antitumor activity of B7H6-specific CAR-T cell was evaluated. Venetoclax-resistant B7H6 CAR-T cell were designed and the synergistic effect of venetoclax and B7-H6 CAR-T cells was tested in vitro and in vivo.

B7H6 is highly expressed in SCLC tumors. CAR-T cell against B7H6 displayed antigen-specific antitumor efficacy. BCL-2(D103E)-expressing CAR-T cells showed resistance to venetoclax-induced apoptosis. The combinational treatment of venetoclax and BCL-2(D103E)-expressing B7H6-targeting showed potent anti-SCLC effect in vitro and in vivo.

Our findings suggest that the combination of BCL-2 mutant-expressing B7H6-targeting CAR-T cells and venetoclax could be a promising novel strategy against B7H6-expressing SCLCs and other solid tumors, providing the foundation for CAR-T cells and proapoptotic small molecules therapy in patients with SCLCs in a clinical trial.

The addition of a programmed death-ligand 1 (PD-L1) inhibitor, either atezolizumab or durvalumab, to platinum-etoposide prolonged survival in a limited subset of patients with extensive-stage small-cell lung cancer (ES-SCLC). Preclinical studies demonstrated synergistic antitumor activity of combined vascular endothelial growth factor receptor and PD-L1 inhibition in SCLC. Since bevacizumab added to platinum-etoposide was safe and active in ES-SCLC, we investigated the efficacy of atezolizumab, bevacizumab, carboplatin, and etoposide as first-line treatment of ES-SCLC.

The CeLEBrATE study is an Italian multicentric single-arm phase II trial of carboplatin (area under the curve 5 ml/min), etoposide (100 mg/sqm), bevacizumab (7.5 mg/kg), and atezolizumab (1,200 mg) every 3 weeks (q3w) for four to six courses, followed by bevacizumab and atezolizumab maintenance q3w in patients with ES-SCLC and no contraindications to immunotherapy or antiangiogenic therapy. Patients with asymptomatic brain metastases were eligible. Prophylactic cranial irradiation and consolidation thoracic external radiotherapy were not permitted while on study treatment. Primary endpoint was overall survival (OS) rate at 1 year.

53 patients were enrolled (45.3% women, median age 65 years) and received at least one dose of study treatment. At a median follow-up time of 23.4 months (95% CI: 21.1 to 26.0), the 1-year OS rate was 61.8% (90% CI: 50.7% to 72.8%; p=0.04), with a median OS of 12.9 months (95% CI: 11.6 to 17.5). Median progression-free survival was 6.2 months (95% CI: 5.4 to 6.6) and objective response rate was 83.3% (95% CI: 69.8% to 92.5%). Grade 3-4 adverse events were reported in 34 patients (64.2%) leading to dose reductions in 24 (45.3%), and dose delays in 39 (73.9%) and 32 (69.6%) during the induction and maintenance phase, respectively. 19 (35.8%) treatment-related serious adverse events were reported.

The CeLEBrATE study met its primary objective demonstrating a signal of efficacy of bevacizumab, atezolizumab, carboplatin, and etoposide in the first-line treatment of patients with ES-SCLC.

GOIRC-01-2019 ML41241, Eudract Number: 2019-003798-2.

Extensive-stage small-cell lung cancer (SCLC) has a poor prognosis, but recently, the combination of immunotherapy and chemotherapy has improved treatment outcomes in some patients, and treatment plans may vary depending on the individual's general condition and tumor response. In addition, intrathoracic tumor control remains a major challenge for this disease. In the current study, we aim to share our clinical experience and demonstrate that consolidative high-dose thoracic radiotherapy effectively reduces intrathoracic tumor recurrence while maintaining acceptable treatment-related toxicities.

The medical records of 81 SCLC patients treated at Korea University Guro Hospital from January 2019 to December 2023 were reviewed retrospectively. Among them, 22 patients with extensive-stage SCLC who had a favorable tumor response after systemic therapy, including those with oligo-progressive disease limited to the thoracic region and suitable for curative local therapy, received consolidative radiotherapy. A total dose of 52.5 Gy in 25 fractions was administered over 5 weeks to all patients with extensive-stage SCLC.

The median follow-up time was 22 months (range: 8-59 months), with the median follow-up period after completing consolidative radiotherapy being 13 months (range: 4-35 months). In-field local recurrence occurred in only one patient after consolidative thoracic radiotherapy. Most importantly, 10 patients with oligo-progressive disease at the thoracic site, at the time of tumor response, remained stable without further intrathoracic in-field recurrence. Additionally, no severe cases of radiation pneumonitis or esophagitis were observed. Based on our institution's experience, consolidative high-dose thoracic radiotherapy is well-tolerated and associated with fewer intrathoracic recurrences, leading to improved long-term survival in carefully selected patients with extensive-stage SCLC. Given these findings, we believe consolidative radiotherapy should be considered more proactively in clinical practice. Furthermore, these results may help guide the design of future clinical trials.

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer, representing about 15% of cases worldwide. Despite advances in imaging, such as low-dose CT, which have increased diagnostic rates, survival outcomes for SCLC patients have remained stagnant. Recent studies have only focused on radiomics, which extracts detailed quantitative features from imaging, with clinical risk factors to improve prognostic models. Therefore, this study aimed to develop a clinical-radiomics fusion nomogram based on computed tomography (CT) to estimate progression-free survival (PFS) in patients diagnosed with SCLC. By integrating radiomics features extracted from CT with clinical data, this model provides personalized prognostic assessment for clinicians. Its clinical utility lies in aiding treatment decision-making by offering more accurate prognostic evaluation, optimizing therapeutic strategies, and identifying high-risk patients at an early stage, ultimately improving overall survival and quality of life.

To develop the nomogram model, 95 patients diagnosed with pathologically confirmed SCLC between January 1, 2013, and December 31, 2023, were included in the study cohort. Participants were randomly divided into training and validation cohorts in a 7:3 ratio. Radiomics features associated with PFS were generated using the least absolute shrinkage and selection operator (LASSO) along with univariate and multivariate analyses. Additionally, in the training cohort, both univariate and multivariate analyses using Cox regression were conducted to identify the significant clinical risk factors influencing PFS. The predictive performance of the clinical and clinical-radiomics fusion nomogram were evaluated using the concordance index, calibration plots, and decision curve analysis (DCA).

Five radiomics features were selected and used to calculate the radiomics score (Rad-score). The radiomics features were significantly associated with PFS (hazard ratio: 0.5765, 95% confidence interval: 0.3641-0.9128, p < 0.05). Three clinical risk factors significantly associated with PFS were identified: neuron-specific enolase (NSE), carbohydrate antigen 125 levels (CA125), and treatment type, such as surgery. The clinical-radiomics fusion nomogram model (C-index:0.744) demonstrated superior performance compared to the clinical nomogram model (C-index: 0.718) in the training cohort. DCA indicated that the clinical-radiomics fusion nomogram outperformed the clinical nomogram in terms of clinical usefulness.

A CT-based clinical-radiomics fusion nomogram was developed to predict PFS in patients with SCLC, which is useful in providing individualized information.

A clinical-radiomics fusion nomogram was constructed to estimate the probability of PFS based on clinical risk factors and the rad-score.

Introduction: Nowadays the prognosis of extended stage (ES) small cell lung cancer (SCLC) patients is poor. However, a high response rate to first-line chemotherapy (CT) and the addition of immune checkpoint inhibitors (ICIs) have notably ameliorated the outcome of these patients. The aim of our study is to compare treatment-related adverse events (TRAEs) between ES- SCLC patients receiving first-line ICIs adding CT and those receiving only CT. Methods: All phase III clinical trials published between 15 June 2008, and 30 June 2024, likenessing ICIs adding systemic CT and only CT in treatment-naïve ES-SCLC patients were retrieved. Results: Twenty-six types of adverse events were included, grouped into ten categories, for a total of 43,391 observations (observations in immune group n = 22,643 and in placebo group n = 20,748) and 9831 events. Our analysis suggested a statistically significant increase in hematological events in patients receiving ICIs plus CT compared with CT alone. Conversely, blood pressure alterations such as hypertension were more frequent in patients treated with CT alone. Conclusions: Despite our analysis confirming the manageable safety profile of chemoimmunotherapy, this remains an issue to be further investigated.

Immune checkpoint inhibitors (ICIs) combined with platinum-doublet chemotherapy (ICI-chemo) have become the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, the effect of ICI-chemo on the efficacy of subsequent chemotherapy remains unknown. This study aimed to investigate the efficacy of second and subsequent treatments of SCLC with and without ICI combination therapy.

We performed an analysis of patients with ES-SCLC between January 2015 and June 2023. The ICI-chemo groups were defined as patients who received ICI-chemo as first-line therapy between September 2019 and June 2023, after ICI-chemo was reimbursed in Japan. The non-ICI-chemo groups were defined as patients who received platinum-doublet therapy between January 2015 and August 2019 and were considered eligible for ICI-chemo.

In total, 224 patients were included (91 and 133 patients who received ICI-chemo and non-ICI-chemo, respectively). There were no significant differences in patient characteristics between the groups. There was no significant difference in progression-free survival (PFS) and overall survival (OS) for first-line treatment between the two groups. The median PFS and OS periods for second-line treatment were 3.9 and 3.9 months and 10.3 and 10.7 months in the ICI-chemo and non-ICI-chemo groups, respectively, without significant difference. Most patients in both groups received amrubicin as the second-line treatment. Moreover, the PFS and OS periods for third-line treatment were not significantly different between the ICI-chemo and non-ICI-chemo groups.

In ES-SCLC, there is no significant additive effect on PFS and OS of second- and subsequent line treatments following ICI-chemo at first-line treatment.

Immune checkpoint blockade is, as of today, the most successful form of cancer immunotherapy, with more than 43 % of cancer patients in the US eligible to receive it; however, only up to 12.5 % of patients respond to it. Similarly, adoptive cell therapy using bioengineered chimeric antigen receptorT (CAR-T) cells and T-cell receptor (TCR) cells has provided excellent responses against liquid tumours, but both forms of immunotherapy have encountered challenges within a tumour microenvironment that is both lacking in tumour-specific T-cells and is strongly immunosuppressive toward externally administered CAR-T and TCR cells. This review focuses on understanding approved checkpoint blockade and adoptive cell therapy at both biological and clinical levels before delving into how and why their combination holds significant promise in overcoming their individual shortcomings. The advent of next-generation checkpoint inhibitors has further strengthened the immune checkpoint field, and a special section explores how these inhibitors can address existing hurdles in combining checkpoint blockade with adoptive cell therapy and homing in on our cancer target for long-term immunity.

Over the past 5 decades, substantial advances in oncology have reshaped cancer care, reflecting the dynamic role of internal medicine physicians in patients' journey from screening to diagnosis, treatment, and surveillance. This review highlights 10 landmark studies from 2024 that address emerging therapies and evolving clinical standards. Immunotherapy remains a central focus, with checkpoint inhibitors redefining the management of solid tumors and showing expanded applications across disease sites and earlier stages of disease. Targeted therapies and antibody-drug conjugates, including trastuzumab deruxtecan and enfortumab vedotin, are enhancing precision treatment options in metastatic cancer. Meanwhile, advances in supportive care, such as magnetic resonance imaging-guided prostate cancer screening, ponsegromab for cachexia, and celiac plexus radiosurgery for pain, show enhanced symptom management and quality of life for patients. These innovations highlight the critical role of multidisciplinary approaches, where internal medicine physicians contribute to co-management and toxicity monitoring, ultimately optimizing patient care. By staying current with these developments, internal medicine physicians are positioned to navigate complex oncologic care, ensuring that the benefits of novel therapies are maximized while mitigating their challenges.