Small Cell Lung Cancer Research Articles

Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Prognostic Nutritional Index as Prognostic Markers for Lung Carcinoma.

Aims/Background Lung cancer (LC) remains one of the most common malignant tumours worldwide, and assessment of its progression is important for ensuring better prognostic outcomes for patients. This study was designed to explore the prognostic role of certain indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) in patients with LC, to help clinics to better determine the prognosis of patients with LC, and to allow them to intervene in a timely manner. Methods A retrospective analysis of 116 initially diagnosed patients with LC in China from 2018 to 2020 was conducted. The counts of neutrophils (NEU), lymphocytes (LYM), and monocytes (MON), as well as albumin levels, were obtained from laboratory databases. The PNI was calculated using a specific formula. The progression-free survival (PFS) curves were plotted using the Kaplan-Meier method, and the Log-rank test was used to compare survival among different groups. The potential prognostic role of these indicators was assessed with univariate and multivariate regression analysis. Results Multivariate Cox regression demonstrated that the PNI (hazard ratio (HR): 0.513, 95% confidence interval (CI): 0.288-0.917, p = 0.024), NLR (HR: 2.038, 95% CI: 1.128-3.682, p = 0.018), and tumour type (small cell lung cancer vs. non-small cell lung cancer) (HR: 2.145, 95% CI: 1.308-3.520, p = 0.003) were significantly associated with PFS. The median PFS for patients with low and high PNI was 10 and 11.5 months, respectively. Conclusion The NLR, PLR, and PNI are all significantly associated with the prognostic survival of LC patients.

Implementing the optimized hippo-avoidance prophylactic cranial irradiation for limited-stage small cell lung cancer by tomotherapy and volumetric modulated arc therapy.

Hippo-avoidance prophylactic cranial irradiation (HA-PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall-off and compensate for setup errors. Most studies recommend a 5-mm margin, while it could be optimized to a 2-mm expansion. Here, we showed the details of optimized HA-PCI for limited-stage small cell lung cancer (LS-SCLC). This cohort study reviewed patients with LS-SCLC receiving optimized HA-PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo-related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test-Revised (HVLT-R) scores in different time points was conducted. The Kaplan-Meier method was used to calculate the survival rates. A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40-7.44) and 7.63 Gy (IQR: 7.14-8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric-modulated arc therapy [VMAT]). The decline of HVLT-R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow-up of 52 months (95% CI: 47.2-56.7), the 2-year overall survival and progression-free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located <2 mm from the hippocampus. Optimized HA-PCI could achieve similar dose limitation by TOMO and VMAT techniques with favorable efficacy and minor toxicity.

Prognostic Factors for Patients with Small-Cell Lung Cancer Treated with Chemoimmunotherapy: A Retrospective Multicenter Study

Background: This study aimed to investigate prognostic factors for predicting the survival of patients with extensive-disease-stage small-cell lung cancer treated with chemoimmunotherapy. Methods: Patients were classified according to overall survival (OS): favorable corresponded to an OS ≥ 24 months, moderate corresponded to an OS of 6–24 months, and poor corresponded to an OS &lt; 6 months. Multivariate Cox regression analyses were used to evaluate prognostic factors. Results: Of 130 patients, the proportions of performance status decline and liver metastasis were significantly higher in the poor-prognosis group. With regard to the laboratory findings, neutrophil/lymphocyte ratios and albumin levels differed significantly among the groups. Multivariate analysis showed that the independent prognostic factors for OS were liver metastasis and decreased albumin levels (&lt;3.5 mg/dL). After classifying the patients into three groups according to the quantities of these prognostic factors, the OS differed significantly among the groups (18.3 vs. 13.5 vs. 3.8 months; p &lt; 0.001). The incidence of immune-related adverse events (irAEs) was higher in patients without these prognostic factors than in those with both (36% vs. 5%; p = 0.01). Conclusion: Liver metastasis and decreased albumin levels are independent unfavorable prognostic factors. Patients with both prognostic factors showed unfavorable OS; however, patients without these factors may have a favorable prognosis but be at greater risk of irAEs.

First-line chemoimmunotherapy for patients with small-cell lung cancer and interstitial lung abnormality: CIP risk and prognostic analysis.

Patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy face a potential risk of developing checkpoint inhibitor-related pneumonitis (CIP). However, there is no clear understanding of the specific link between interstitial lung abnormality (ILA) and CIP in patients with small-cell lung cancer (SCLC). In addition, the prognosis of SCLC patients with ILA who receive chemoimmunotherapy is uncertain. Our study aimed to investigate the effect of ILA on the occurrence of CIP in SCLC patients receiving first-line chemoimmunotherapy and to assess its relationship with prognosis. We conducted a retrospective analysis of SCLC patients who received chemoimmunotherapy as a first-line treatment between January 2018 and April 2024. The diagnosis of ILA was assessed by two experienced pulmonologists based on pretreatment chest computed tomography images. We investigated independent risk factors for CIP using logistic regression analysis and factors affecting PFS and OS using Cox regression analysis. A total of 128 patients with SCLC were included in the study. ILA was present in 41 patients (32.03%), and CIP occurred in 16 patients (12.50%). In multivariate logistic regression analysis, previous ILA (OR, 5.419; 95% CI, 1.574-18.652; p = 0.007) and thoracic radiation therapy (TRT) (OR, 5.259; 95% CI, 1.506-18.365; p = 0.009) were independent risk factors for CIP. ILA (HR, 2.083; 95% CI, 1.179-3.681; p = 0.012) and LDH (HR, 1.002; 95% CI, 1.001-1.002; p < 0.001) were statistically significant for increased mortality risk in multivariate Cox regression analysis. In SCLC patients receiving first-line chemoimmunotherapy, baseline ILA is a risk factor for CIP and is associated with poorer prognosis.

Improving Patient Understanding and Outcomes in Lung Cancer Using an Animated Patient's Guide with Visual Formats of Learning.

Lung cancer patient education resources that address barriers to health literacy, improve understanding, and demonstrate improved patient outcomes are limited. Our study aim was to evaluate and report on learner knowledge improvement and intent to implement behavior change, and validate the benefits of the You and Lung Cancer website and YouTube resources. Our study occurred from November 2017 to December 2023. We evaluated audience reach (visit sessions, unique visitors, country origins, page views) and calculated top views by media type (animations, expert videos, patient videos). We assessed the impact and commitment to change through learner surveys (areas of interest, intention to modify behaviors, and intention to discuss disease management with providers) and tested the knowledge of learners pre- and post-reviewing of website content. Our program reached 794,203 views globally; 467,546 were unique visitors; and 243,124 (51%) were unique visitors from the USA. Of US visitors, 46% identified as lung cancer patients. These were patients in treatment (38%), survivors (8%), family members or caregivers (21%), and healthcare providers (14%) with other audiences unspecified (19%). Three areas of highest learner importance were the animations "Understanding Non-Small Cell Lung Cancer" (180,591), "Staging of Lung Cancer" (144,238), and "Treatment and Management of Small Cell Lung Cancer" (49,244). Our study confirmed areas of importance to lung cancer patients and suggests that visual formats of learning, such as animations, can mitigate health literacy barriers and help improve patient understanding and outcomes. Exporting this format of learning to other cancers has the potential to benefit patients and improve health outcomes.

Osimertinib (Tagrisso)

Canada’s Drug Agency (CDA-AMC) recommends that Tagrisso in combination with pemetrexed and platinum-based chemotherapy should be reimbursed by public drug plans for the first-line treatment of patients with locally advanced (not amenable to curative therapies) or metastatic non–small cell lung cancer (NSCLC) which harbours epidermal growth factor receptor (EGFR) exon 19 deletions (Ex19del) or exon 21 (L858R) substitution mutations if certain conditions are met. Tagrisso plus chemotherapy should only be covered to treat adult patients (aged ≥ 18 years) who have nonsquamous NSCLC; whose tumours have spread to other parts of the body, returned after treatment, or cannot be removed by surgery or radiation; whose tumours harbour EGFR Ex19del or L858R substitution mutations; and who are in relatively good health. Tagrisso should not be covered to treat patients who have a history of breathing difficulties caused by scarring and inflammation in the lung tissue; who have a history of heart problems associated with their heart taking longer to recharge between beats or their heart beating too fast, too slow, or in an irregular way; or, who have already been treated for NSCLC with treatments affecting their entire body (except for treatments given at least 6 months before the tumour returned, as a first step to shrink a tumour before the primary treatment, or as an additional treatment after the primary treatment to lower the risk of the tumour returning). Tagrisso should only be reimbursed if it is prescribed in combination with pemetrexed and platinum-based (i.e., cisplatin or carboplatin) chemotherapy by clinicians with expertise in treating NSCLC, and the cost of Tagrisso is reduced. Reimbursement of Tagrisso plus chemotherapy should be discontinued if a patient’s cancer grows or spreads, or if treatment is unacceptably toxic to the patient.

Clinical characteristics and treatment management of combined large cell neuroendocrine carcinoma, a subtype of large cell neuroendocrine carcinoma.

Combined large cell neuroendocrine carcinoma (CLCNEC) is a rare neuroendocrine carcinoma, accounting for approximately 10% of large cell neuroendocrine carcinoma (LCNEC). Mainly composed of coexisting adenocarcinoma components, with strong invasiveness and poor prognosis. The treatment regimen for CLCNEC mainly refers to complete surgical resection as the first choice in the early stage, while patients with stage II or higher require adjuvant treatment. At present, research on CLCNEC is mostly small sample and retrospective, and there is no consensus on whether molecular typing and treatment should be carried out. There is considerable controversy over whether it should be managed as small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Therefore, in order to solve the problem of confusion in the selection of treatment regimens for CLCNEC, while also considering the therapeutic effects, this article summarizes and analyzes previous studies, fully seeks evidence, and boldly proposes new therapeutic insights: the etoposide-platinum (EP) regimen serves as the basis for adjuvant therapy; In addition, SCLC/NSCLC-CLCNEC can be distinguished based on presence of RB1 and TP53 co-mutation, and targeted therapy or NSCLC type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) can be used in combination or sequentially for NSCLC-CLCNEC.

The efficacy of Veliparib in combination with chemotherapy in the treatment of lung cancer: systematic review and meta-analysis.

This meta-analysis aims to examine the effectiveness of veliparib, a poly ADP-ribose polymerase inhibitor, in combination with chemotherapy in treating bronchogenic carcinoma. PubMed, Cochrane, Scopus, and Web of Science were searched for eligible randomized controlled trials comparing veliparib plus chemotherapy to standard chemotherapy in adult lung cancer patients, until July 2023. The main outcomes were overall survival (OS) and progression-free survival (PFS). This meta-analysis included six studies encompassing 2,136 patients. Veliparib has a slight OS improvement over placebo, HR = 0.91, 95% CI [0.83 to 1.0], p = 0.05. Veliparib offers more OS benefit in the subpopulation of non-small cell lung cancer (NSCLC) than small-cell lung cancer (SCLC), HR = 0.89, 95% CI [0.81,0.99], p = 0.03 and HR = 1.00, 95% CI [0.79, 1.28], p = 0.97, respectively. There was no significant PFS benefit between the two groups, HR = 0.92, 95% CI [0.81-1.01], p = 0.08). Veliparib has a marginal inclination for overall survival improvement, more so in NSCLC, with an acceptable safety profile. Our results merit the pursuit of better-powered trials to support further the extent of veliparib's effectiveness in lung cancer patients. PROSPERO (CRD42023453705).

Paraneoplastic neurological syndrome and its impact on the treatment outcomes of small-cell lung cancer: A single-center retrospective analysis.

Paraneoplastic neurological syndrome (PNS) is associated with small-cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real-world data from patients with PNS complicated by SCLC. Patients diagnosed with Stage II-IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3-4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23). A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS.

Abstract A017: Identifying proliferative and immune-modulatory drivers of small cell lung cancer (SCLC)

Abstract Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer that causes an estimated 200,000 patient deaths globally every year. Most (&amp;gt;70%) patients present with extensive stage (ES)-SCLC, and the disease primarily presents with a neuroendocrine (NE), immune-desert phenotype, with low expression of antigen-presenting machinery genes. Despite limited immune infiltration in the tumor, SCLC has reproducibly responded to immune checkpoint blockade. IMpower133 was a pivotal Phase III trial that added atezolizumab (anti-PD-L1) to platinum/etoposide chemotherapy for treatment of first-line ES-SCLC, which led to the first approval of an immune checkpoint blockade strategy in SCLC. While the inclusion of atezolizumab to the treatment regimen has extended the survival of some patients, SCLC remains an unmet medical need with a mOS of 12.3 months. Furthermore, we lack a deep molecular understanding of factors mediating response and resistance to standard of care therapies in SCLC. To understand the genetic drivers of SCLC that could be linked to immunotherapy resistance, we analyzed the matched whole-exome sequencing and RNA-seq data from baseline tumor samples collected from the IMpower133 trial. Previously, we applied the non-negative matrix factorization (NMF) approach to the RNA-seq data, which clustered patients into four subsets of SCLC, with varying degrees of immune infiltration, neuroendocrine program activation, and clinical benefit from immunotherapy. Notably, we identified an inflamed-neuroendocrine (I-NE) subset of patients that exhibit longer overall survival with chemoimmunotherapy compared to chemotherapy alone, and an inflamed-non-neuroendocrine (I-nonNE) subset of patients that did not show a similar benefit from the addition of immunotherapy to chemotherapy. Here, we interrogated the matched WES data for recurrent alterations that may identify subsets of tumors with distinct immunological features. We identified several genes whose alterations significantly affected the enrichment of immune-related gene signatures. In particular, we identified MANF and CSK, genes previously shown to be potential tumor suppressors, as genes whose alteration associates with an “immune desert” transcriptional program. Specifically, genetic deletions or low RNA expression was associated with significantly decreased gene expression of gene signatures associated with lymphocytes, macrophages, and antigen presentation machinery. These data suggest a potential mechanism by which commonly inactivated tumor suppressors may shape the “immune desert” phenotype of SCLC. Further work is needed to determine if and how these genes may directly or indirectly modulate the tumor-immune interaction. Citation Format: Myung Chang Lee, Velimir Gayevskiy, Stefanie Morris, Minu K Srivastava, Namrata S Patil, Stephen V Liu, Martin Reck, Sanjeev Mariathasan, David S Shames, David P MacPherson, Robert J Johnston, Barzin Y Nabet. Identifying proliferative and immune-modulatory drivers of small cell lung cancer (SCLC) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A017.

Risk stratification model for foreseeing overall survival in Chinese patients with initially metastatic small-cell lung cancer.

The study was outlined to develop and approve a nomogram and chance stratification demonstrate for foreseeing overall survival of Chinese patients with at first metastatic small-cell lung cancer (SCLC). We collected information from the Surveillance, Epidemiology, and End Results (SEER) database approximately Chinese SCLC patients with at first distant metastases between 2010 and 2015. Patients with incomplete data about the follow-up time or clinicopathological information were excluded. The included patients were randomized into the training and validation set. Univariate and multivariate Cox proportional hazard regression models were performed. By integrating the significant variables screened, a prescient nomogram and risk stratification model were developed. In addition, we collected 198 small-cell lung cancer patients with metastasis at diagnosis from the case database of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine as an external validation cohort. In all, 421 patients were screened from the SEER database. Multivariate examination showed that age (P = .049), sex (P = .001), grade (P = .008), chemotherapy (P = .001), liver metastasis (P = .001), and pleural invasion (P = .012) were independent prognostic factors. The C-indicator of the nomogram to anticipate overall survival was higher than that of the eighth edition of the American Joint Committee on Cancer Tumor Node Metastasis classification system (0.75 vs 0.543; P < .001). A risk stratification model was encouraged to be created to precisely classify patients into 2 prognostic bunches. The survival rates anticipated by the nomogram appeared to have critical qualifications from the Kaplan-Meier curves in the entire SEER cohort. Calibration curves and survival predictions also showed strong accuracy and consistency in the external validation cohort. The nomogram provided a clear prognostic superiority over the traditional Tumor Node Metastasis system. It could help clinicians make individual risk predictions for initially metastatic Chinese SCLC cancer patients and give necessary treatment recommendations.

Number of involved nodal stations predicts survival in small cell lung cancer

BackgroundIn small cell lung cancer (SCLC), the pathological N category is identical to it in non-small cell lung cancer (NSCLC) and remains unchanged over a decade. Here we verified the discriminability of number of involved nodal stations (nS) in SCLC and compared its efficacy in predicting survival with currently used pathological nodal (pN) staging.MethodsWe retrospectively analyzed the patients who received operations and were pathologically diagnosed as SCLC at Shanghai Pulmonary Hospital between 2009 and 2019. X-tile software was adopted to determine optimal cut-off values for nS groups. Kaplan–Meier method and Cox regression analysis were used to compare survival between different groups. Decision curve analysis (DCA) was employed to evaluate the standardized net benefit.ResultsA total of 369 patients were included. The median number of sampled stations was 6 (range 3–11), and the median number of positive stations was 1 (range 0–7). The optimal cutoff for nS groups was: nS0 (no station involved), nS1-2 (one or two stations involved), and nS ≥ 3 (three or more stations involved). Overall survival (OS) and relapse-free survival (RFS) were statistically different among all adjacent categories within the nS classification (p < 0.001, for both OS and RFS between each two subgroups), but survival curves for subgroups in pN overlapped (OS, p = 0.067; RFS, p = 0.068, pN2 vs. pN1). After adjusting for other confounders, nS was a prognostic indicator for OS and RFS. The DCA revealed that nS had improved predictive capability than pN.ConclusionsOur cohort study demonstrated that the nS might serve as a superior indicator to predict survival than pN in SCLC and was worth considering in the future definition of the N category.

MA19.05 Dynamic Immune Profile of Peripheral Blood Predicts Immunotherapy Efficacy and Prognosis in Small Cell Lung Cancer

MA19.05 Dynamic Immune Profile of Peripheral Blood Predicts Immunotherapy Efficacy and Prognosis in Small Cell Lung Cancer

OA10.06 Impact of Brain Metastases on Safety and Efficacy of MK-6070, a DLL3-Targeting T Cell Engager, in Small Cell Lung Cancer

OA10.06 Impact of Brain Metastases on Safety and Efficacy of MK-6070, a DLL3-Targeting T Cell Engager, in Small Cell Lung Cancer

P3.13D.01 Proteomic Characterization of Antibody Drug Conjugate Target Expression Profiles in Small Cell Lung Cancer (SCLC)

P3.13D.01 Proteomic Characterization of Antibody Drug Conjugate Target Expression Profiles in Small Cell Lung Cancer (SCLC)

P3.03I.12 Modulation of EMT Increases the Activity of Lurbinectedin in Small Cell Lung Cancer

P3.03I.12 Modulation of EMT Increases the Activity of Lurbinectedin in Small Cell Lung Cancer

P3.13D.10 Clinical Outcomes of Transformed Small-Cell Lung Cancer Versus Extensive Primary Small-Cell Lung Cancer

P3.13D.10 Clinical Outcomes of Transformed Small-Cell Lung Cancer Versus Extensive Primary Small-Cell Lung Cancer

OA04.05 SHR-A1921, A TROP-2 Targeted Antibody-Drug Conjugate (ADC), In Patients (pts) with Advanced Small-Cell Lung Cancer (SCLC)

OA04.05 SHR-A1921, A TROP-2 Targeted Antibody-Drug Conjugate (ADC), In Patients (pts) with Advanced Small-Cell Lung Cancer (SCLC)

MA17.13 DLL3-targeted CAR-T Therapy of Small Cell Lung Cancer Utilizing Circular RNA

MA17.13 DLL3-targeted CAR-T Therapy of Small Cell Lung Cancer Utilizing Circular RNA

P1.09A.03 Concurrent Combination of EGFR-TKIs and Thoracic Radiation Therapy for Metastatic Non Small Cell Lung Cancer Patients

P1.09A.03 Concurrent Combination of EGFR-TKIs and Thoracic Radiation Therapy for Metastatic Non Small Cell Lung Cancer Patients