Small Cell Lung Cancer Patients Research Articles

Consensus on immunotherapy for small cell lung cancer(2024 edition)

Lung cancer is one of the malignant tumors with high morbidity and mortality worldwide. Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is closely associated with tobacco exposure, accounting for 13% to 15% of all lung cancer cases. It is characterized by a high proliferation rate and exceptional metastatic capacity. At the time of diagnosis, approximately 70% of the patients have metastasized and are classified as extensive-stage small cell lung cancer (ES-SCLC). From 1980 to 2018, chemotherapy and radiotherapy were the main treatment strategies for SCLC. Etoposide combined with platinum has remained the standard first-line treatment for ES-SCLC. Although SCLC is very sensitive to initial treatment, the majority of patients have disease progression within 6 months, and treatment options after recurrence are very limited, and the median survival time is only about 8-10 months. The advent of immune checkpoint inhibitors (ICIs), particularly programmed death-ligand 1 (PD-L1) and programmed death -1 (PD-1) inhibitors, has brought new hope to patients with SCLC. PD-1/PD-L1 plus chemotherapy have significantly prolonged overall survival of patients with ES-SCLC, which has become the new standard of first-line treatment for ES-SCLC. Currently, a raised number of immune checkpoint inhibitors (ICIs) have been approved in China for the treatment of SCLC, providing more treatment options for SCLC patients. To further standardize the clinical practice of SCLC immunotherapy, the "Expert Consensus on Immunotherapy for SCLC" has been developed based on domestic and international guidelines, consensus, and relevant medical evidence, aiming to provide reference and guidance for domestic clinicians.

Prophylactic cranial irradiation for small cell lung cancer in the era of immunotherapy and molecular subtypes.

Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis, whereas its metastatic capacity carries a predilection for the brain. Although prophylactic cranial irradiation (PCI) has been used to address this problem, upcoming alternatives might necessitate reflection of its application in SCLC treatment. The addition of immunotherapy to treatment guidelines has provided a new strategy for the management of brain metastases. Complementation of immunotherapy with active MRI surveillance could potentially replace PCI and avoid irradiation-related cognitive side effects. SCLC's molecular profile is heterogeneous, with differential response to treatment modalities between subgroups. Investigation of these variances might be essential to improve therapeutic outcomes in SCLC patients. The role of PCI in SCLC treatment must be examined in light of immunotherapy. We summarize recent results, bearing SCLC subtypes and therapeutic vulnerabilities in mind, to derive tailored treatment strategies for SCLC patients in future settings.

Lurbinectedin in extensive-stage small-cell lung cancer: a brief report of the IFCT-2105 LURBICLIN study

Small-cell lung cancer (SCLC) is a highly aggressive type of lung cancer. Lurbinectedin is recommended as second-/third-line treatment for advanced, previously treated SCLC. LURBICLIN is a nationwide, non-interventional, retrospective chart review study, based on the cohort of consecutive patients enrolled in the named patient use for lurbinectedin in France. A total of 312 patients were included. Lurbinectedin was delivered as second-line therapy in 138 (44%) patients. Grade 3-4 treatment-related adverse events were observed in 28 (9%) and 15 (5%) patients, respectively. Objective response rate (ORR) to lurbinectedin was 22% in the intention-to-treat population. After a median follow-up of 20.8 months, median progression-free survival (PFS) was 1.9 months [95% confidence interval (CI) 1.8-2.0 months]. At multivariate analysis, chemotherapy-free interval (CTFI) ≥ 90 days was an independent predictor of higher PFS [hazard ratio (HR)= 0.64, 95% CI 0.50-0.84, P < 0.0001]. The median overall survival (OS) was 4.7 months (95% CI 4.0-5.4 months). At multivariate analysis, performance status < 2 and CTFI ≥ 90 days were independent predictors of higher OS (HR= 0.71, 95% CI 0.53-0.95, P= 0.03; and HR= 0.58, 95% CI 0.44-0.76, P < 0.0001, respectively). Overall, 147 (47%) patients had initiated subsequent systemic treatments. LURBICLIN confirms the activity of lurbinectedin in patients with SCLC with a manageable safety profile. Lurbinectedin monotherapy provides an alternative option for SCLC patients.

Prognostic impact of elevated C-reactive protein and procalcitonin in patients with extensive-stage small cell lung cancer.

Small cell lung cancer (SCLC) constitutes around 15% of lung cancer cases and stands as the primary cause of cancer-related fatalities in men and the second leading cause in women globally. In this study, our objective was to evaluate the levels of C-reactive protein (CRP) and procalcitonin (PCT) in newly diagnosed extensive-stage SCLC patients without evidence of infection. We aimed to demonstrate that elevated CRP and PCT levels may not solely indicate infection but could also be elevated in malignancies. Furthermore, we sought to correlate these marker levels with patient and disease characteristics to elucidate the relationship between these inflammation markers and disease progression. A total of 115 patients who were pathologically and radiologically diagnosed with extensive-stage SCLC between January 2020 and December 2022 and who had received no prior treatment were included in the study. The Kaplan-Meier analysis revealed a median progression-free survival (PFS) of 7.46 months [95% confidence interval (CI), 6.85-8.07] and a median overall survival (OS) of 10.50 months (95% CI, 8.69-12.30) for all patients. In the group with elevated PCT, the median PFS was 6.73 months (95% CI, 3.92-9.54), whereas it was 7.86 months (95% CI, 7.13-8.59) in the group with normal PCT (P = 0.002). Similarly, the median OS was 9.10 months (95% CI, 5.61-12.58) in the elevated PCT group and 11.66 months (95% CI, 9.59-13.74) in the normal PCT group (P = 0.006). Patients with elevated procalcitonin (PRC) levels at the time of diagnosis exhibited shorter PFS and OS durations compared to patients with normal PRC levels. Furthermore, elevated CRP has also been demonstrated to correlate with poorer prognosis in extensive-stage SCLC.

Small cell lung cancer with liver metastases: from underlying mechanisms to treatment strategies.

Small cell lung cancer (SCLC) represents an aggressive neuroendocrine (NE) tumor within the pulmonary region, characterized by very poor prognoses. Druggable targets for SCLC remain limited, thereby constraining treatment options available to patients. Immuno-chemotherapy has emerged as a pivotal therapeutic strategy for extensive-stage SCLC (ES-SCLC), yet it fails to confer significant efficacy in cases involving liver metastases (LMs) originating from SCLC. Therefore, our attention is directed towards the challenging subset of SCLC patients with LMs. Disease progression of LM-SCLC patients is affected by various factors in the tumor microenvironment (TME), including immune cells, blood vessels, inflammatory mediators, metabolites, and NE substances. Beyond standard immuno-chemotherapy, ongoing efforts to manage LMs in SCLC encompass anti-angiogenic therapy, radiotherapy, microwave ablation (MWA) / radiofrequency ablation (RFA), trans-arterial chemoembolization (TACE), and systemic therapies in conjunction with local interventions. Prospective experimental and clinical investigations into SCLC should prioritize precise and individualized approaches to enhance the prognosis across distinct patient cohorts.

Annotated test-retest dataset of lung cancer CT scan images reconstructed at multiple imaging parameters

Quantitative imaging biomarkers (QIB) are increasingly used in clinical research to advance precision medicine approaches in oncology. Computed tomography (CT) is a modality of choice for cancer diagnosis, prognosis, and response assessment due to its reliability and global accessibility. Here, we contribute to the cancer imaging community through The Cancer Imaging Archive (TCIA) by providing investigator-initiated, same-day repeat CT scan images of 32 non–small cell lung cancer (NSCLC) patients, along with radiologist-annotated lesion contours as a reference standard. Each scan was reconstructed into 6 image settings using various combinations of three slice thicknesses (1.25 mm, 2.5 mm, 5 mm) and two reconstruction kernels (lung, standard; GE CT equipment), which spans a wide range of CT imaging reconstruction parameters commonly used in lung cancer clinical practice and clinical trials. This holds considerable value for advancing the development of robust Radiomics, Artificial Intelligence (AI) and machine learning (ML) methods.

The impact of Prophylactic cranial irradiation on the prognosis of patients with limited-stage small cell lung cancer in the MRI era

PurposesTo evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of MRI surveillance.MethodsLimited-stage SCLC patients with complete remission (CR) or partial remission (PR) of tumor after definitive chemo-radiotherapy (CRT) were retrospectively analyzed. Survival data were calculated by Kaplan-Meier methods, Cox proportional hazards model was applied for multivariate prognostic analysis.ResultsBetween June 2002 and January 2017, 620 patients with limited-stage SCLC were accrued in our study. After CRT, 228 (36.8%) patients achieved CR, of whom, 29 patients did not receive PCI, among the rest 199 patients, 172 (86.4%) received brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 25.6 months, the cumulative BM rate was 17.1% and 37.9% in patients who received or did not receive PCI (P = 0.011). The median survival time was 30.2 months and 30.5 months, respectively and the 1 -, 3 -, 5-year survival rates were 93.7%, 42.9%, 35.8% and 83.4%, 46.5%, 41.9%, respectively (P = 0.98). Multivariate analysis indicated that baseline KPS ≥ 90 was a favorable independent prognostic factor for OS in CR patients (HR: 0.33, 95% CI: 0.23–0.46, P = 0.000). After CRT, 392 (63.2%) patients achieved PR, 53 cases did not receive PCI and 310 (91.4%) of the remaining 339 patients received brain MRI before PCI. With a median follow-up time of 15.5 months, the cumulative brain metastasis rate was 12.7% and 46.2% respectively (P = 0.000). The median survival time was 25.7 months and 18.6 months, respectively. The 1 -, 3 -, and 5-year survival rates were 87.6%, 40.2%, 29.2% and 75.7%, 16.7%, 10.3% (P = 0.000). Baseline KPS ≥ 90 (HR: 0.32, 95% CI: 0.25–0.41, P = 0.000) and PCI (HR: 0.57, 95% CI: 0.41–0.79, P = 0.001) were favorable prognostic factors for OS in PR patients.ConclusionsIn this study, PCI significantly reduced the incidence of BM in patients with limited-stage SCLC who were evaluated as CR and PR after CRT, but it has no significantly positive impact on overall survival in CR patients. Further prospective randomized studies were warranted.

Abstract PR005: Leveraging mass cytometry for phenotyping CTCs in SCLC liquid biopsies: Tracking therapy resistance at a personalized level

Abstract Liquid biopsies present a promising, minimally invasive procedure through which clinicians can assess and monitor disease status by interrogating circulating tumor cell (CTC) and immune cell phenotypes. In the case of Small-cell lung cancer (SCLC) – a type of lung cancer characterized by aggressive growth, dismal prognosis and limited treatment options - leveraging liquid biopsies and CTCs for evaluating disease status would be of great benefit, given that biopsies are scarce. Furthermore, SCLC CTC numbers are higher compared to other cancers, presenting a unique opportunity to utilize them for assessing SCLC therapy resistance and identifying new targetable markers. In this study, we leverage mass cytometry (i.e. CyTOF) to phenotype SCLC CTC phenotypes in longitudinal clinical specimens to assess therapy resistance at a personalized level. By using CyTOF - a multiplex cytometric approach that enables interrogation of 30-50 protein markers per single cell – we show that we are able to identify and analyze a significant number of CTCs and their heterogeneous expression profiles. To achieve this, we first optimized a CyTOF panel of ∼25-30 antibodies by using SCLC cell lines and blood specimens from healthy donors and SCLC patients. We show that by using this approach, we are able to identify and phenotype SCLC CTCs by using the combination of CD45 (negative expression) and CD56 positive expression with further validation achieved by TTF1 and SCLC subtype transcription factor expression (NEUROD1, POU2F3 and ASCL1). This approach avoids enriching for specific CTC epithelial phenotypes that express surface markers that fluctuate during epithelial- mesenchymal transition (EMT) (e.g. EpCAM, a common marker for isolating CTCs). For parallel immune profiling we assessed among others CD8/CD4 (T cells) and CD11b/HLA-DR (Myeloid-derived suppressor cells, MDSCs) expression. We then proceeded to interrogate CTC phenotypic differences in the naïve vs relapsed setting as well as dynamic changes in longitudinal blood specimens from SCLC patients by evaluating markers that describe immune suppression activity (PD-L1) and EMT status (E-Cadherin, Vimentin, MUC1, Twist and Slug). Importantly, we show that with our approach we can track in real time therapeutic targets that are currently being tested in clinical trials or have been recently FDA approved (e.g. pYAP and DLL3) and found that MUC1 and pYAP are significantly increased in CTCs detected in blood specimens of SCLC relapsed patients. Our immune profiling showed an increase of MDSC percentages and a decrease in the CD4/CD8 T cell ratio in the relapsed setting. Finally, when we used PHENOSTAMP, a previously developed reference EMT map for assessing EMT phenotypes in lung cancer clinical specimens, we observed an increase of EMT heterogeneity in CTCs in relapsed patients. Our study highlights the translational power of our approach in utilizing CyTOF for longitudinally tracking CTCs directly in SCLC patient liquid biopsies towards assessing therapy response and resistance at a personalized level. Citation Format: Loukia G Karacosta, Sayantan Bhattacharyya, Allison Stewart, Ashley Victorian, Ester F Lujan, Shafqat Ehsan, Subin Kim, Alberto Duarte, Runsheng Wang, Benedict Anchang, Jing Wang, Lauren Byers. Leveraging mass cytometry for phenotyping CTCs in SCLC liquid biopsies: Tracking therapy resistance at a personalized level [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR005.

Actin Dysregulation Induces Neuroendocrine Plasticity and Immune Evasion: A Vulnerability of Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is aggressive with limited therapeutic options. Despite recent advances in targeted therapies and immunotherapies, therapy resistance is a recurring issue, which might be partly due to tumor cell plasticity, a change in cell fate. Nonetheless, the mechanisms underlying tumor cell plasticity and immune evasion in SCLC remain elusive. CRACD, a capping protein inhibitor that promotes actin polymerization, is frequently inactivated in SCLC. Cracd knockout (KO) transforms preneoplastic cells into SCLC tumor-like cells and promotes in vivo SCLC development driven by Rb1, Trp53, and Rbl2 triple KO. Cracd KO induces neuroendocrine (NE) plasticity and increases tumor cell heterogeneity of SCLC tumor cells via dysregulated NOTCH1 signaling by actin cytoskeleton disruption. CRACD depletion also reduces nuclear actin and induces EZH2-mediated H3K27 methylation. This nuclear event suppresses the MHC-I genes and thereby depletes intratumoral CD8+ T cells for accelerated SCLC tumorigenesis. Pharmacological blockade of EZH2 inhibits CRACD-negative SCLC tumorigenesis by restoring MHC-I expression and immune surveillance. Unsupervised single-cell transcriptomics identifies SCLC patient tumors with concomitant inactivation of CRACD and downregulated MHC-I pathway. This study defines CRACD, an actin regulator, as a tumor suppressor that limits cell plasticity and immune evasion and proposes EZH2 blockade as a viable therapeutic option for CRACD-negative SCLC.

RADT-47. CLINICAL OUTCOMES AFTER SURGICAL RESECTION OF BRAIN METASTASES IN SMALL CELL LUNG CANCER PATIENTS

Abstract Small cell lung cancer (SCLC) has a high propensity to metastasize to the brain. Radiotherapy is the primary treatment for SCLC brain metastases. Whole brain radiotherapy (WBRT) has been the standard of care, but recent studies show similar overall survival (OS) in patients treated with upfront stereotactic radiosurgery (SRS). Surgery does not typically have a role in SCLC although it can provide relief of neurologic symptoms and pathologic diagnosis. We sought to determine the clinical outcomes of patients who underwent surgical resection of SCLC brain metastases. A retrospective chart review of SCLC patients treated at UPMC from 2010 – 2022 was performed. OS after resection was estimated using the Kaplan-Meier method with log-rank test. 4,213 patients were diagnosed with SCLC, of which 715 patients (17%) had synchronous brain metastases at initial diagnosis. Forty patients underwent resection of SCLC brain metastases, all of whom were symptomatic. The median diameter of the resected brain metastases was 3.8 cm (range 1.7 – 8 cm). Seventy-five percent (n=30) had resection of synchronous brain metastases and 25% (n=10) had resection of metachronous brain metastases. Median OS for the surgical cohort was 13.6 months (interquartile range (IQR), 3.4 – 21.9 months). Patients with metachronous and synchronous brain metastases had median OS of 6.8 months (IQR, 2.8 – 24.6 months) and 14.3 months (IQR, 3.6 – 20.4), respectively. Of patients with synchronous brain metastases (n=30), 53% (n=16) received post-operative WBRT, 40% (n=11) received post-operative SRS and 10% (n=3) died within 7 weeks of surgery. Median OS of patients with synchronous brain metastases treated with WBRT and SRS were 11.9 months (IQR, 3.8 – 21.7) and 19.0 months (IQR, 14.6 – 30.3), respectively, and the difference was not statistically significant (p=0.53). Surgery for SCLC brain metastases is uncommon. Patients who received SRS versus WBRT post-operatively for synchronous brain metastases had no difference in OS.

RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor

Neuroendocrine tumor (NET) is a rare malignant tumor, notably small cell lung cancer (SCLC), a type of lung neuroendocrine tumor, which has a survival rate of less than 7%. Although various biomarkers including CHGA (Chromogranin A), INSM1 (Insulinoma-associated protein 1), and SYP (Synaptophysin) are extensively used for the diagnostic testing of NET, their diverse specificities and sensitivities are acknowledged as limitations. Here, we demonstrate that RepID (Replication initiation determinant protein), a component of CRL4 (Cullin-RING ubiquitin E3 ligase 4), holds promise as a biomarker for identifying NET and SCLC. Analysis of the Cancer Cell Line Encyclopedia (CCLE) via the CellMinerCDB portal reveals a high correlation between RepID transcript levels and mRNA expression of NE signature genes. Additionally, RepID protein is highly expressed in SCLC patient tissues and a subset of SCLC cell lines. Viability analysis following treatment with pevonedistat and SZL-P1-41 in SCLC cell lines and human SCLC-organoid models indicates that RepID expression determines the sensitivity to CRL-targeting anti-cancer drugs. These findings suggest that RepID represents a novel biomarker for NET and SCLC, and insights from RepID research in these cancers could lead to innovative therapeutic strategies.

Neoadjuvant immune checkpoint inhibitor reduced recurrence in operable NSCLC patients with pathological complete response: a retrospective analysis

BackgroundThis study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non–small cell lung cancer (NSCLC) patients with pathologic complete response (pCR).MethodsFrom January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients’ survival status were analyzed.ResultsSquamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046).ConclusionThe study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.

Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundIrinotecan is a standard chemotherapeutic agent in small cell lung cancer (SCLC), however, as a common adverse reaction, diarrhea limits the use of irinotecan. Shengjiang Xiexin decoction (SXD) has been used in various gastrointestinal diseases in China two thousand years ago. We designed this clinical trial to supply more evidences on the use of SXD as prophylaxis for irinotecan-induced diarrhea, especially for high-risk population predicted by gene testing of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1).MethodsIn this clinical trial, 120 patients with SCLC were recruited from six hospitals in China. They received two cycles of chemotherapy, meanwhile they were randomized to receive SXD or placebo for 14 days of oral administration in each cycle of chemotherapy. The primary outcome is the incidence of diarrhea. And secondary outcomes include the the degree of diarrhea and neutropenia, the number of chemotherapy cycles with diarrhea, first occurrence time and duration of diarrhea. To evaluate the effect of SXD on the intestine, a rat model with delayed-onset diarrhea induced by irinotecan was established, and the expression of inflammatory factors including IL-1β, IL-6 and TNF-α, anti-inflammatory factors including IL-10, TGF- β in jejunal tissue was detected by ELISA.Results101 patients (53 in SXD group, 48 in placebo group) completed the trial. The incidence of diarrhea in SXD group and placebo group were 26.42% (14/53) and 52.08% (25/48), respectively (P < 0.05), and the degree of diarrhea also had significant differences (P < 0.05). In UGT1A1 high-risk population, the incidence of diarrhea in two groups were 9.09% and 66.67% (P < 0.05), but there was no significant differences in UGT1A1 low-risk population. The incidence of neutropenia with degree 1–3 between two groups was 20.75% vs 20.83%, 13.21% vs 18.57%, 9.43% vs 20.83% (P < 0.05). No severe adverse events were reported in any group. And animal studies had shown SXD reduced content of IL-1β, IL-6, TNF-α, increased content of IL-10, TGF-β in jejunum tissue.ConclusionsSXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors.Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250. The preliminary protocol of this clinical study has been published in the journal “Trials” in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).

Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era

IntroductionThe role of consolidative thoracic and prophylactic brain radiation for extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether RT has a benefit to overall survival (OS) in patients receiving any systemic therapy and whether this benefit is the same if Chemotherapy (CT) or chemo-immunotherapy (CT-IO) is used. Material/MethodsThe NCDB database was queried from years 2017–2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, be treated 2–6 months from diagnosis, and if treated to the brain received 25 Gy in 10 fractions only. Multi-variable analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS. ResultsThe total number of patients receiving RT/STX or STX alone as well as their median follow-up (months) were (890, 17.0 mn) and (6898, 14.0mn). The median time to the start of STX and RT were 22.9 days and 152 days, respectively. MVA noted that RT had a greater effect on OS (Thorax, Brain, Both Brain/Thorax – HRs = 0.80, 0.77, 0.70) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.06). Selection for radiation depended significantly upon factors affecting OS (HR) including lack of liver metastases, females, age and Charlson co-morbidity index, but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity-score matched OS curves noted the same significant effects of RT on OS in those receiving CT +/- IO, CT-IO, and CT alone with HRs of 0.68/0.68/0.68 for thoracic RT, 0.72/0.72/0.70 for brain RT, and 0.60/0.60/0.60 for brain/thoracic RT, respectively. ConclusionsThe patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy.

Construction and validation of deep learning model for cachexia in extensive-stage small cell lung cancer patients treated with immune checkpoint inhibitors: a multicenter study

Construction and validation of deep learning model for cachexia in extensive-stage small cell lung cancer patients treated with immune checkpoint inhibitors: a multicenter study

Prognostic Nomogram for Predicting Survival in Asian Patients With Small-Cell Lung Cancer: A Comprehensive Population-Based Study and External Verification.

The incidence of small cell lung cancer (SCLC) among Asian patients is on the rise. Nevertheless, there remains a deficiency in precise prognostic models tailored to the specific needs of this patient population. It is imperative to develop a novel nomogram aimed at forecasting the prognosis of Asian SCLC patients. The SEER database supplied data on 661 Asian SCLC patients, who were then divided into training and internal validation sets through a random selection process. In addition, we identified 212 patients from a Chinese medical institution for the purpose of creating an external validation cohort. To forecast survival, we employed both univariate and multivariate analyses. The performance of our nomogram was assessed through calibration plots, the concordance index (C-index), and decision curve analysis (DCA). Five independent prognostic factors were determined and integrated into the nomogram. C-index values for the training and internal validation cohorts were 0.774 (95% confidence interval [CI] = 0.751-0.797) and 0.731 (95%CI = 0.690-0.772), respectively. In the external validation cohort, the C-index is 0.712 (95% CI = 0.655-0.7692). Calibration curves demonstrated highly accurate predictions. When compared to the AJCC staging system, our model exhibited improved net benefits in DCA. Furthermore, the risk stratification system effectively differentiated patients with varying survival risks. We have created a novel nomogram for predicting the survival of Asian patients with SCLC. This nomogram has been subjected to external validation and has shown its superiority over the conventional TNM staging system. It offers a more precise and reliable means of forecasting the prognosis of Asian SCLC patients.

Immune-related adverse events in small-cell lung cancer patients treated with immune checkpoint inhibitors: a comprehensive analysis from the FDA adverse event reporting system.

The discovery and development of immune checkpoint inhibitors (ICIs) have resulted in their application as a novel therapeutic strategy for patients with small-cell lung cancer (SCLC). However, a comprehensive analysis of the potential adverse effects of ICIs in patients with SCLC remains to be conducted. Adverse event (ADE) reports relating to SCLC patients, submitted to the FDA Adverse Event Reporting System (FAERS) from the first quarter of 2013 to the second quarter of 2022, were extracted for analysis. The extracted data were subsequently screened and analyzed using the reporting odds ratio (ROR) method to assess the AE reports. A total of 4,522 ADE reports were obtained from patients with SCLC who had received either chemotherapy alone or a combination of ICIs with chemotherapy. The ROR analysis identified a total of 91 immune-related adverse events in SCLC patients associated with the ICIs (SCLC-irAEs). This study revealed that the adverse effects resulting from irAEs in SCLC patients predominantly affected the hematologic and gastrointestinal systems, with the most severe cases potentially leading to fatality.

Metabolomic Profiling of Large Extracellular Vesicles in Patients Suffering from Small Cell Lung Cancer.

Large extracellular vesicles (lEV) offer a unique window into the metabolism of their cells of orign and dysregulation of lipid metabolism has been described in patients with small cell lung cancer (SCLC). Therefore, metabolomic profiling of patients' lEVs may offer insight into cancer metabolism as well as new potential biomarkers for monitoring disease progression. lEVs were isolated by differential centrifugation from the peripheral blood of SCLC patients and healthy controls. Targeted mass spectrometry was used to analyze the lipid composition of lEVs. After identifying relevant metabolites, biomarker and pathway analysis were conducted. SCLC patients exhibited a distinct metabolic profile compared to healthy controls. The metabolites TG(16:0:_38:3), TG(18:3_35:2), TG(16:0_40:7), Cer(d18:1/26:0), and CE(16:0) are not only able to discriminate between patients and control samples, but are also served as prognostic markers for survival. Patients with high concentrations of these metabolites showed significantly shorter survival times. Pathway analysis revealed alterations in 'sphingolipid metabolism', 'sphingolipid signaling pathway' and 'necroptosis'. Metabolic profiling of lEVs in SCLC patients is feasible and reveals a distinct metabolic profile. High concentrations of identified lipids are associated with poor prognosis.

Association of Plasma Nestin With Response to Immune Checkpoint Inhibitors Combined With Chemotherapy in Extensive-stage Small-cell Lung Cancer: A Pilot Study.

Nestin, an intermediate filament protein expressed in stem/progenitor cells of the developing central nervous system, is involved in the progression and poor prognosis of various malignancies. Difficulties in small-cell lung cancer (SCLC) tissue biopsy reduce the accuracy of immunohistochemistry analyses; therefore, evaluating nestin in blood samples is preferred in clinical practice. This study examined the clinical significance of plasma nestin levels in SCLC. A single-center observational study of patients with untreated SCLC was conducted from 2019 to 2021. We determined plasma nestin levels before and after two treatment cycles, and the results were analyzed in relation to clinical outcome. Twenty-five SCLC patients were enrolled. When patients were divided into high-plasma nestin (h-pNES) and low-plasma nestin (l-pNES) groups based on pre-treatment plasma nestin levels, among nine extensive-stage SCLC (ES-SCLC) patients treated with immune checkpoint inhibitor (ICI) combination chemotherapy, h-pNES patients had shorter progression-free survival and overall survival than l-pNES patients (p=0.0150 and p=0.0353, respectively). CD8/FoxP3- and CD8/CD3-positive T-cell ratios in biopsy specimens from h-pNES patients were lower than those of l-pNES patients (p=0.0458 and p=0.0218, respectively). This pilot study indicated that h-pNES patients exhibited a poorer response to ICI combination chemotherapy than l-pNES patients. Plasma nestin levels are easy to measure in ES-SCLC, in which sufficient tissue is difficult to obtain, and may potentially serve as a predictor of response to ICI combination chemotherapy. A large cohort is needed to investigate the clinical role of plasma nestin.

Clinical characteristics and prognostic factors of epidermal growth factor receptor-mutated non-small cell lung cancer transformed into small-cell lung cancer after treatment

Objective: To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Results: Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%CI: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%CI: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%CI: 7.0-14.2 months), with a median OS of 8.8 months (95%CI: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%CI: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (P=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (HR=0.32, 95%CI: 0.12-0.73, P=0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%CI: 13.0-36.7 months). Conclusions: NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.