To evaluate the value of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) at different risks of brain metastasis (BM).

A retrospective study included 498 LS-SCLC patients from three centers who achieved complete or partial response (CR/PR) after radical chemoradiotherapy. A nomogram was developed using significant factors associated with BM, identified through univariate and multivariate analyses. Patients were stratified into high- and low-risk groups based on risk scores. The incidence of BM was compared between patients with and without PCI in different risk-stratified populations using the log-rank test.

The nomogram included age, start of treatment to the end of radiotherapy (SER), hemoglobin, prognostic nutritional index (PNI), ProGRP, and NSE. The area under the receiver operating characteristics (AUC) of the nomogram for predicting the 2-year probability of intracranial progression-free survival (IPFS) were 0.738, 0.811, and 0.726 in the training, internal validation, and external validation cohorts, respectively. In the low-risk group, no significant differences were observed in BM incidence (p = 0.220), OS (p = 0.679), or PFS (p = 0.616) between PCI and non-PCI groups. In the high-risk group, PCI significantly reduced BM incidence (p < 0.0001) and improved PFS (p = 0.032), while no significant differences were found in OS (p = 0.778). Propensity score-matching analysis showed similar results.

PCI did not improve OS in patients regardless of high or low risk of BM. However, PCI did significantly reduce the incidence of BM and prolong PFS in patients at a high risk of BM.

Small cell lung cancer (SCLC) is characterized by high malignancy and early propensity for metastasis, and modest response to immunotherapy due to the immunosuppressive microenvironment. Surgical intervention has shown benefits in treating early-stage SCLC. However, most patients experience recurrence after surgery. The factors associated with relapse free survival in these patients remain unclear. We collected operation specimens from ten early-stage SCLC patients (N0M0), conducted long-term follow-up, and grouped them based on disease status. Subsequently, we performed a retrospective analysis using single-cell spatial imaging mass cytometry to explore the characteristics of tumor cells and differences in the tumor microenvironment, especially the single-cell constitute of immune cells, between the two groups. We found that, in early-stage SCLC, tumor cells display pronounced heterogeneity, both intra-group and inter-group. Patients with early recurrence are characterized by a distinct subpopulation of tumor cells with high Ki-67 expression. Non-relapse patients demonstrate better infiltration of M1 macrophages and stromal cells. Neighborhood analysis suggested that positive interactions between macrophages, stromal cells, and T cells with tumor cells may benefit patient prognosis. Additionally, recurrent tumor cells might enhance their metastatic capacity and remodel the microenvironment through upregulation of GranzymeB or reduction of c-Myc expression. In conclusion, SCLC tumor cells demonstrate tumor heterogeneity and microenvironmental changes in the early clinical stages. A higher proportion of M1 macrophages is associated with prolonged postoperative survival in early-stage SCLC patients. This research provides novel insights and evidence for treating and preventing postoperative recurrence in SCLC.

In lung cancer, KRAS mutations, especially the G12C, favor aggressive tumor growth and resistance to standard therapies. Although first-generation inhibitors of KRAS G12C, such as sotorasib and adagrasib, are highly effective in early-phase studies, resistance invariably develops under selective inhibition pressure and rarely leads to sustained long-term treatment benefits. As a novel approach to targeting KRAS mutations in lung cancer, PROTAC (Proteolysis Targeting Chimera) technology is explored in this review. The PROTACs take advantage of the cell's ubiquitin-proteasome system to selectively degrade KRAS proteins, overcoming the dilemma of a lack of traditional binding sites and the means of resistance. We review recent progress with KRAS-specific PROTACs and their mechanisms, clinical application, and effectiveness at targeting primary KRAS oncogenes and secondary drivers and signaling pathways contributing to therapeutic resistance. Also, the synergies between PROTACs and immunotherapies or chemotherapies are further amplified. This review also underscores PROTAC technology's promise to advance precision medicine by providing durable treatment options for KRAS-driven lung cancers. It addresses future directions for optimizing PROTAC efficacy, bioavailability, and patient-specific applications.

Small cell prostate cancer (SCPC) is a rare, aggressive disease with limited clinical data to guide treatment. In this retrospective study, we evaluated clinical, treatment, and outcomes data for patients with SCPC.

Patients with SCPC were selected from CancerLinQ Discovery®, a United States-based de-identified clinical database derived from the electronic health records of over 60 medical oncology organizations. A diagnosis of SCPC was made based on a tumor histology code of small cell carcinoma. The primary outcome of this study was assessing first-line systemic therapy within 1 year of diagnosis of SCPC.

74 patients with SCPC who received systemic therapy between 2010-2023 were identified. The majority had documented metastatic disease (45 patients, 60.8%) and a low PSA (median 2.8 ng/dL) at SCPC diagnosis. Platinum chemotherapy plus etoposide was the most common systemic treatment (62, 83.8%) and carboplatin plus etoposide was the most common regimen (42, 56.8%) used in the first line. Median overall survival (OS) was 8.3 months for patients with metastatic SCPC. Patients treated with cisplatin plus etoposide had improved survival versus those receiving carboplatin plus etoposide (odds ratio 3.15, 95% CI 1.57-6.30; p = 0.001). 45.9% of patients with SCPC received second-line systemic therapies, which were highly varied.

This contemporary real-world data represent one of the largest descriptions of the treatment of SCPC. Clear consensus on the optimal systemic therapy for SCPC is lacking. While additional research is needed, real-world practice patterns can serve as a resource when considering a treatment approach for this rare disease.

Currently, the accepted standard management of limited-stage small cell lung cancer (LS-SCLC) is concurrent chemoradiotherapy; however, the thoracic radiotherapy regimen remains controversial. Therefore, this meta-analysis aims to compare efficacy and safety of different thoracic radiotherapy regimens.

Relevant randomized controlled trials (RCTs) were sourced in PubMed, Cochrane Library, Web of Science, and EMBASE to assess antitumor effects (overall survival, OS; progression-free survival, PFS; overall response rate, ORR) and toxicity (adverse effects, AEs).

Of the 2225 screened articles, 8 RCTs (involving 2363 patients) were included. The control arm was defined as 45 Gy/30f BID. The experimental arms were categorized into three groups: high-dose hyper-fractionation (hHyper-RT: 54 Gy/30f BID, 60 Gy/40f BID), hypo-fractionation (Hypo-RT: 42 Gy/15f QD, 65 Gy/26f QD), and conventional fractionation (Conv-RT: 45 Gy/25f QD, 66 Gy/33f QD, 70 Gy/35f QD). Compared with 45 Gy/30f BID, hHyper-RT (54 Gy/30f BID and 60 Gy/40f BID) showed improved OS (HR = 0.55, 95 % CI: 0.37---0.82; HR = 0.69, 95 % CI: 0.48---0.99), hHyper-RT (54 Gy/30f BID) and Hypo-RT (65 Gy/26f QD) improved PFS (HR = 0.70, 95 % CI: 0.49---0.99; HR = 0.78, 95 % CI: 0.62---0.98), whereas OS and PFS with Conv-RT was comparable to that of 45 Gy/30f BID. AE development was comparable among 45 Gy/30f, hHyper-RT, and Hypo-RT, whereas Conv-RT (45 Gy/25f QD) reduces the risk of esophagitis and grade 3-5 esophagitis (RR = 0.70, 95 % CI: 0.58-0.85; RR = 0.50, 95 % CI: 0.35-0.72). No significant difference was found for ORR, pneumonitis or grade 3-5 pneumonitis between the study arms.

Compared with 45 Gy/30f BID, hHyper-RT (54 Gy/30f BID and 60 Gy/40f BID) improved OS, while hHyper-RT (54 Gy/30f BID) and Hypo-RT (65 Gy/26f QD) prolonged PFS in LS-SCLC patients, with accepted toxicity.

Small cell lung cancer (SCLC) is associated with high mortality and limited therapeutic options. There is increasing recognition that SCLC harbors molecular heterogeneity. Using a new liquid biopsy assay, it is demonstrated that SCLC subtypes, as determined by patient tumor tissue staining and cell lines, can be accurately identified by measuring the mRNA expression of subtype transcription factors (ASCL1, POU2F3, and NEUROD1) in circulating exosome-rich extracellular vesicles (Exo). Additionally, upregulation of Delta-like ligand 3 (DLL3) mRNA in Exo and its membrane protein (mProtein) in extracellular vesicles associated with tumor (tEV) may distinguish both limited- and extensive-stage SCLC patients from high-risk smokers, with AUC/ROC values of 0.836 and 0.839, respectively. By incorporating Exo-ASCL1 and Exo-POU2F3 mRNA expression with DLL3 Exo-mRNA/tEV-mProtein expression, the classifier enhances the AUC/ROC to 0.912 and 0.963 for limited- and extensive-stage SCLC patients, respectively.

Some patients are candidates for either surgical resection or stereotactic body radiotherapy for treatment of stage I lung cancer. We refined a previously developed decision tool about this treatment choice and evaluated interest in a personalized risk calculator.

We conducted qualitative interviews from October 2023 to May 2024 with patients who had been treated for stage I lung cancer at a Midwestern comprehensive cancer center and with clinicians who treat such patients.

Participants responded positively to the tool and indicated that it could support decisions if provided before or during conversations following diagnosis. There was no consensus on which clinician should deliver the tool. Suggested tool adaptations focused on clarifying eligibility for options and accurately describing the range of patients' recovery experiences. Participants were open to the idea of a personalized risk calculator but expressed concerns about accuracy and interpretation of the results.

Decision tools can help clinicians and patients collaborate on care decisions. Future work will explore opportunities to incorporate personalized risk information and evaluate this decision tool with a diverse group of patients deciding on treatment for stage I lung cancer.

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.

On May 16, 2024, tarlatamab-dlle (IMDELLTRA®) received approval as the first FDA DLL3 targeting bispecific T-cell engager (BiTE®) therapy indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) who have experienced disease progression on or after platinum-based chemotherapy. This case study provides insights into the regulatory mechanisms, including global expedited pathways, special designations, and US FDA's Oncology Center of Excellence initiatives, which played a key role in the expedited development, review, and approval of the tarlatamab marketing authorization application (MAA) globally.

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.

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.

Primary small cell carcinoma of the esophagus (SCCE) is an aggressive carcinoma with a rare incidence. Most patients were diagnosed with stage III-IV and have a poor prognosis. The poor therapeutic outcomes of SCCE reveal the need for more rational therapies.

We retrospectively reviewed 15,463 patients with esophageal carcinoma from January 2015 to December 2020. 235 (1.52%) patients were pathologically diagnosed with primary SCCE. Clinical characteristics and treatment information were extracted from medical records. All statistical analyses were performed with the SPSS software. Patients were divided into radiotherapy (RT) group and non-RT group. The chi-square test was conducted to analyze the difference in baseline characteristics and propensity score matching (PSM) was used to balance the patient characteristics. Univariate and multivariate analysis was used to identify independent prognostic factors and calculated the estimated hazard ratio (HR) and 95% confidence interval (CI). The Kaplan-Meier method was used to draw survival curves, calculate the median overall survival (OS), and compare prognosis between groups with the log-rank p test. The two-tailed p value less than 0.05 indicated a significant difference.

The median OS was 15.2 months (range:13.4-17.1 months). The addition of RT improved median OS from 14.3 months to 16.5 months, but the difference was not statistically significant (p = 0.657). After PSM, the median OS of the RT group was longer than the non-RT group (16.5 months vs. 11.5 months, p < 0.001). Multivariate analysis identified RT (HR: 0.711, 95%CI: 0.533-0.949, p = 0.020), surgery (HR: 0.490, 95%CI: 0.365-0.660, p < 0.001), and smoking history (HR: 1.335, 95%CI: 1.010-1.765, p = 0.042) as independent prognostic factors. Subgroup analysis showed that RT was not a prognostic factor in patients with surgery (p = 0.450), but could significantly improve OS in patients without surgery (HR: 0.585, 95%CI: 0.415-0.824, p = 0.002). Both middle and lower thoracic SCCE patients could benefit from the addition of RT. RT could improve OS regardless of Ki67 expression level. Subgroup analyses also indicated that stage IV, age ≥ 60, no smoking history, pure SCCE, Syn-positive, CgA-positive, CD56-positive patients could benefit from RT.

SCCE patients could benefit from RT, especially those without surgery. Further studies are required for confirmation of the conclusion.

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.

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a critical intracellular signaling pathway that is pivotal in various cellular functions. It is in senescence, survival, and growth under normal physiological and pathological conditions, including neoplasms. Additionally, this pathway has been recognized as essential for the regulation of the cell cycle. Several previous studies have indicated that the PI3K/Akt signaling pathway can be influenced by various natural products, with resveratrol (3,4',5-trihydroxy-trans-stilbene) being a particularly important phytoalexin polyphenol in this context. This review explores the impact of the PI3K/Akt signaling pathway on the initiation and advancement of various cancerous conditions and the potential of resveratrol to target this signaling mechanism. The review begins by summarizing the anti-tumor capabilities of resveratrol and then emphasizes the significant role of the PI3K/Akt signaling pathway in the progression of multiple malignancies. Finally, we discuss the therapeutic effects of resveratrol on human neoplasms, from brain cancers to gastrointestinal malignancies, through regulation of this signaling cascade.

An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC).

A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay.

①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01).

CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.

The integration of artificial intelligence (AI) in automatic image segmentation systems offers a novel approach to evaluating the clinical target volume (CTV) in small cell lung cancer (SCLC) patients. Utilizing imaging recurrence data, this study applies a recursive feature elimination algorithm to model and predict patient prognoses, aiming to enhance clinical guidance and prediction accuracy.

This research analyzed data from SCLC patients who received curative radiotherapy from January 1, 2010, to December 30, 2021, and had comprehensive follow-up records including pre- and post-treatment imaging. An AI-driven image segmentation system segmented the initial CTV, evaluating 110 clinical parameters. The recursive feature elimination method selected pertinent features, and a random forest-based recursive prediction model was developed to establish a clinically viable recurrence prediction model.

1. Local Control Analysis: A study of 180 patients, with a median follow-up duration of 36 months, revealed that 94 experienced recurrences, while 86 did not. Factors influencing local control rates included gender (male), age (>60 years), T stage, smoking index, and tumor size. Notably, tumor size (≥ 5cm) emerged as an independent factor significantly impacting local control rates, with a Hazard Ratio (HR) of 1.635 (95% CI: 1.055-2.536, p=0.028). 2. Recurrence Analysis: Tumor size (≥ 5cm) was also closely linked to patient local control rates, with a 3-year Local Control Rate Failure (LCRF) contrasting sharply between larger tumors (61.1%) and smaller tumors (86.7%, p=0.004). Upon analyzing recurrence patterns among 94 patients, a total of 170 instances were examined. Recurrence was most prevalent in regions 10R, 10L, 4R, and 7, accounting for 67.65% (115/170) of cases, while regions 2L and 3P showed no recurrences. The initial region of the primary tumor or metastatic lymph nodes was identified as a critical recurrence area, with a 100% recurrence rate in patients whose initial tumor region included 10 specific regions. The recurrence rates for initial tumor regions involving 4R, 7, 11R, and 11L ranged between 41.6% and 45.5%. 3. Development of a recurrence prediction model: utilizing an AI-powered automatic image segmentation system, multidimensional partition parameters, including 110 clinical variables, were analyzed. The recursive feature elimination method facilitated efficient feature selection. From this, a recurrence prediction model for small cell lung cancer was developed using a random forest algorithm, achieving a clinically significant accuracy rate of 77%. This model provides a reliable basis for enhancing the clinical application and decision-making process for medical practitioners.

The utilization of AI-based automatic image segmentation system for delineating the initial CTV has proven pivotal. Analysis and modeling of recurrent images reveal that the initial GTV and GTVnd are critical regions for recurrence. Leveraging partition parameter and variable information, we constructed a clinically viable recurrence prediction model. This model significantly aids in guiding the precise clinical targeting of treatment areas, demonstrating the potential of AI to enhance patient management and treatment outcomes in small cell lung cancer.

This document reviews the evidence supporting different imaging modalities and techniques used to evaluate patients with a history of lung cancer. It focuses on the imaging evaluation of patients treated for stage I-III non-small-cell lung cancer and small-cell lung cancer, whether using individual modalities or combinations. Guidelines for both routine surveillance of stage I-III lung cancer and for the evaluation of suspected recurrence or disease progression are provided. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

The therapeutic landscape for small cell lung cancer (SCLC) has remained stationary for decades, with chemotherapy representing the sole treatment strategy, with a modest survival benefit. The addition of immune checkpoint inhibitors (ICIs) to standard first-line chemotherapy for SCLC was a considerable milestone. However, despite high overall response rates, this strategy failed to deliver long-term benefits for most patients, who continue to face a poor prognosis. Over the last few years, a deeper knowledge of the molecular biology of SCLC and the impressive advancements in drug development, have led to the generation of novel classes of systemic therapies that promise to revolutionize the current therapeutic scenario. Among the various therapeutic approaches in development, T-cell Engagers (TCE) and antibody-drug conjugates (ADCs) stand out due to their unique structural characteristics and mechanisms of action. These therapies represent a paradigm shift from traditional monoclonal antibody (mAb) and chemotherapy regimens, allowing direct engagement of multiple targets associated with tumor progression. In this review, we provide an overview of current drug development in SCLC, specifically focusing on these new agents, summarizing available evidence, and tracking future directions.

Lung cancer is the most lethal malignancy worldwide, having the highest incidence rate. This is a heterogeneous disease classified according to its histological and molecular characteristics. Depending on these, different therapeutic approaches have already been approved for lung cancer treatment targeting genetic alterations or even the immune system. Nonetheless, other therapies are being studied to continuously improve the care and survival of lung cancer patients. Among them, immunotherapies are one of the main targets of investigation to try and combat the ability of some malignant cells to evade anti-tumor responses mediated by the immune system. Cancer vaccine development has emerged as a promising approach to strengthen the patient's immune system and combat the disease, especially mRNA vaccines. Currently, there are several ongoing studies investigating the therapeutic efficacy of mRNA vaccines in lung cancer treatment alone or combined with other therapeutic drugs. This review aims to highlight the importance of immunotherapy in lung cancer treatment, presenting the most recent advances particularly in mRNA-based vaccines as well as the challenges and future perspectives.

Small cell lung cancer (SCLC) is one of the malignancies with the worst prognosis, and there have been no major breakthroughs in its treatment for a long time. The majority of patients are diagnosed at the extensive stage, where the only option is chemotherapy, and even the addition of immune checkpoint inhibitors results in only modest benefits. The characterization of the molecular mechanisms behind therapy resistance has relevance in finding novel therapeutic approaches. Previous studies showed the possibility of annexin A1's (ANXA1) involvement in the immunosuppressive tumor microenvironment in SCLC, and there are studies showing the direct effects of ANXA1 modulation on cancer cell aggressiveness.

We aimed to characterize the roles of ANXA1 expression using publicly available transcriptomic data, the RNA-seq-based predictive algorithms EPIC and ESTIMATE, and immunohistochemistry on patient samples. For the in vitro studies, we silenced ANXA1 expression with short hairpin RNA in three SCLC cell lines, measured the growth rate with the trypan blue exclusion assay, assessed the chemosensitivity to cisplatin and etoposide with the Presto BlueTM viability assay, and performed Western blots to assess changes in the levels of metabolic and mesenchymal markers and transcriptional drivers.

ANXA1-high tumors are associated with significantly increased immune infiltrates, stromality, and tumor-associated macrophages (TAMs). The ANXA1 protein is expressed on tumor cells and TAMs at the tissue level. ANXA1 silencing in H841 cells did not affect the growth rate; in SW1271 cells, shANXA1 cells grew significantly slower than shCTRL cells. Meanwhile, in H1048 cells, proliferation was significantly faster. Despite the different growth rates of the tested cell lines, ANXA1 silencing decreased the chemosensitivity to both cisplatin and etoposide in all three cell lines. Gene expression changes in mesenchymal markers, metabolic markers, dominant transcriptional drivers, and immune-relevant molecules were also characterized.

This is the first comprehensive characterization of ANXA1 in SCLC to reveal its role in the tumor's cell biology and the TME, aiming to boost further research in the field.

Small cell lung cancer (SCLC) is a type of high-grade neuroendocrine malignancy with low gene mutation. Chemotherapy is the major treatment strategy, but long-term clinical application often leads to drug resistance. Etoposide is a first-line drug approved by the US Food and Drug Administration for SCLC treatment, but etoposide-resistance is a problem. In this study, a SCLC cell line with etoposide-acquired resistance, H1048-ER, was constructed through a concentration gradient increasing method, and its resistance to etoposide was investigated in vitro and in a zebrafish model. Through transcriptome sequencing, real-time reverse transcription-quantitative polymerase chain reaction, and bioinformatic analyses of H1048-ER vs. H1048 cells, 51 differentially expressed genes were found to be significantly enriched in "collagen degradation" and "MET/FAK signaling activation in ECM". Among them, six genes (COL11A1, COL26A1, COL4A3, COL4A4, LAMA4, and LAMC1) had strong correlations with the prognosis of lung cancer. They may be key factors in the acquired etoposide resistance of H1048-ER cells. H1048-ER cells showed cross-resistance to cisplatin but were sensitive to doxorubicin and temozolomide. Our study provides novel insights into etoposide resistance in SCLC and affords the potential treatment options after etoposide resistance.

The role of malignant cell count in pleural fluid as a potential predictor of survival remains under investigation. This study aims to assess the relationship between malignant cell count in pleural effusion and mortality in patients with malignant pleural effusion (MPE).

This retrospective cohort study was conducted at a tertiary referral and research hospital, including treatment-naive patients diagnosed with MPE. Univariate and multivariate Cox regression analyses were employed to identify independent predictors of mortality.

A total of 63 patients were included in the analysis, with a male predominance (39 males, 61.9 %) and a mean age of 65.7 ± 12.5 years. The majority (76.2 %) of patients had NSCLC. Patients were stratified based on malignant cell count into two groups: those with <1700 cells/2mm² and those with ≥1700 cells/2mm². The two groups were similar in demographics, blood and pleural fluid parameters, and comorbidities. Multivariate Cox regression analysis revealed that male gender (HR: 4.14, 95 % CI: 1.65-10.39), active smoking (HR: 2.99, 95 % CI: 1.25-7.16), and malignant cell count (HR: 0.23, 95 % CI: 0.09-0.56) were independent predictors of mortality.

Our findings indicate that a malignant cell count of <1700 cells/2mm², male gender and active smoking are independent prognostic factors associated with increased mortality in patients with MPE. Further large-scale prospective studies are necessary to confirm the clinical relevance of cytological malignant cell counts and to explore the viability and functional significance of these cells.

Rechallenging immune checkpoint inhibitors(ICIs) after resistance to initial ICIs plus chemotherapy(chemo-ICIs) remains uncertain in advanced small cell lung cancer(SCLC).

The study retrospectively enrolled advanced SCLC patients who received ICIs after developing resistance to chemo-ICIs during hospitalization at Hunan Cancer Hospital from January 2020 to November 2023. The clinical outcomes and prognosis factors for ICIs rechallenge were further analyzed.

A total of 175 patients were included, of which 82(46.86 %) patients had primary resistance(PR) and 93(53.14 %) patients developed acquired resistance(AR). The progression-free survival(PFS), objective response rate (ORR), and disease control rate (DCR) of the total group were 3.3 months,16.57 %, and 53.71 %, respectively. The AR group exhibited significantly longer PFS compared to the PR group (4.5 months vs. 3.2 months, p = 0.012). In the PR group, a significantly longer PFS was found for ICIs rechallenge with interval treatment than without interval treatment(4.2 months vs. 3.1 months, p = 0.031). Within the AR group, the "new immunotherapy plus new chemotherapy" regimen showed a significantly longer PFS compared to the regimen of "maintain immunotherapy plus new chemotherapy" (8.3 months vs. 3.2 months, p = 0.014). The multivariate COX regression analyses demonstrated that both resistance pattern(p = 0.007) and treatment regimen(p = 0.039) independently served as risk factors for PFS in ICIs rechallenge.

Our study suggests that rechallenge of ICIs could be considered as a potential therapeutic strategy for advanced SCLC after progression from chemo-ICIs, particularly in patients with AR.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness and safety of anti-TIGIT inhibitors in combination with PD-1 inhibitors or PD-L1 inhibitors compared to treatment with PD-1 inhibitors or PD-L1 inhibitors in the first-line treatment of advanced NSCLC. To assess the effectiveness and safety of anti-TIGIT inhibitors in combination with chemotherapy and PD-1 inhibitors or PD-L1 inhibitors compared to treatment with chemotherapy plus PD-1 inhibitors or PD-L1 inhibitors in the first-line treatment of advanced NSCLC.

Chemoimmunotherapy (CT/IO) with immune checkpoint inhibitors has recently become the standard of care for extensive-stage small cell lung cancer (ES-SCLC). Given the uncertain role of consolidation thoracic radiotherapy (cTRT) in this setting, we conducted a real-world study to evaluate the efficacy and safety of cTRT in ES-SCLC patients receiving first-line CT/IO. We performed a retrospective analysis of ES-SCLC patients treated with first-line CT/IO in Slovenia from December 2019 to June 2024. Patient characteristics, treatment patterns, survival outcomes, and adverse events were analyzed, with subgroup comparisons based on cTRT administration. Among 208 patients (median age: 66 years), median overall survival was 12.1 months (95% CI: 10.6-13.7). cTRT was administered to 46 patients (22.1%), who had fewer metastases. cTRT was associated with improved OS (17.0 vs. 10.8 months; p < 0.001) and was an independent OS predictor (HR = 0.58, p = 0.035). Grade ≥ 3 adverse events were similar (26.1% vs. 21.3%), though pneumonitis occurred more frequently with cTRT (6.5% vs. 0%, p = 0.001). cTRT may improve survival in ES-SCLC patients treated with CT/IO, with no significant increase in toxicity apart from pneumonitis. Further prospective studies are needed.

An 80-year-old woman presented with weight loss, elevated pro-gastrin-releasing peptide levels, and later developed exertional dyspnea. Contrast computed tomography of the chest revealed multiple masses in the left upper lobe of the lung, left hilar and mediastinal lymphadenopathy, and pleural effusion, suggesting pleural dissemination. Additionally, positron emission tomography-computed tomography showed fluorodeoxyglucose uptake in the descending portion of the duodenum and associated wall thickening. Histopathological examination of the bronchoscopic biopsy specimens demonstrated small to intermediate-sized tumor cells with scant cytoplasm, finely granular chromatin, and nuclear molding, supporting the diagnosis of small-cell lung cancer (SCLC). She was diagnosed with extensive-stage SCLC and experienced gastrointestinal bleeding from the suspected duodenal metastasis lesion before the treatment, with severe anemia. She was promptly started on systemic chemotherapy with carboplatin, etoposide, and durvalumab due to clinical urgency and suspicion of duodenal metastasis. Although the pulmonary tumor responded to treatment, gastrointestinal bleeding persisted. The endoscopic biopsy confirmed primary duodenal adenocarcinoma. Surgical resection was not pursued due to the patient's condition, and chemotherapy for SCLC was continued. This case illustrates the importance of synchronous primary cancers in patients with atypical presentations and highlights the need to balance prompt treatment with thorough diagnostic evaluation. Early treatment of the more aggressive cancer allowed clinical stabilization and outpatient management, demonstrating a pragmatic approach to complex oncologic care in elderly patients.

Peripheral facial palsy is commonly associated with benign self-limited conditions. In rare circumstances, it may be the manifestation of underlying malignancy.

We present an unusual case of a 53-year-old woman with previously diagnosed small cell lung cancer (SCLC), who developed sudden-onset peripheral facial palsy. Imaging studies revealed mastoid metastasis with facial nerve involvement and venous sinus thrombosis, despite a normal MRI performed just one month prior. Despite ongoing treatment, the disease showed rapid progression culminating in the patient's death.

Metastatic involvement of the mastoid is extremely rare in SCLC. Such metastases can occur via haematogenous or meningeal spread, resulting in complex clinical phenotypes with mastoid involvement, including facial palsy and venous sinus thrombosis among others.

This case emphasises the importance of individualised assessment in peripheral facial palsy and vigilance regarding unusual metastatic patterns in cancer patients. The rapid clinical deterioration despite appropriate treatment underscores both the aggressive nature of SCLC and the critical need for more effective treatment strategies.

Small cell lung cancer's neuroendocrine nature drives metastasis to unexpected territories, including the rarely affected mastoid region.In patients with peripheral facial palsy and malignancy risk factors, prompt imaging should be considered, even when other suspicious features are absent.Small cell lung cancer evolves rapidly in spite of treatment, requiring vigilance for metastatic complications despite reassuringly normal recent examinations.

In this study, we aimed to analyze the efficacy and failure patterns of contouring target volume based on the residual tumor and decreasing the dose to the area of tumor regression after neoadjuvant therapy in locoregionally advanced head and neck squamous cell carcinoma (HNSCC).

We retrospectively analyzed the patients with locoregionally advanced HNSCC treated by our group from May 2011 to June 2023. All patients received neoadjuvant therapy followed by intensity-modulated radiation therapy. Gross tumor volumes for the primary tumor and metastatic lymph nodes were delineated according to postneoadjuvant extension. The tumor shrinkage after neoadjuvant therapy was included in the high-risk clinical target volume (CTV1) and prescribed a dose of 60 Gy. Kaplan-Meier analysis was employed to calculate local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), overall survival (OS), and distant metastasis-free survival (DMFS). Failure patterns were analyzed by mapping the location and extent of locoregional recurrence onto pretreatment planning CT.

This study included a total of 114 patients, with a median follow-up of 34 months. The 5-year LRFS, RRFS, OS, and DMFS rates were 70.2%, 70.7%, 74.8%, and 73.8%, respectively. Among the 14 patients with recurrences, there were 5 local failures, 6 regional recurrences, and 3 both local and regional recurrences. All local recurrences occurred within the 95% isodose line, classified as in-field failures. Only one regional recurrence was marginal failure. No out-of-field failure was observed.

Reduction of target volume after neoadjuvant therapy and distribution of 60 Gy of dose to the tumor regression area may be feasible.

Profiling studies in small-cell lung cancer (SCLC) have mainly focused on primary tumors, omitting the potential molecular changes that might occur during lymphatic metastasis formation. Here, we assessed the molecular discordance between primary SCLCs and corresponding lymph node (LN) metastases in the light of subtype distribution and expression of clinically relevant proteins.

Comparative profiling of 32 surgically resected primary SCLCs and their LN metastases was achieved by RNA expression analysis and immunohistochemistry (IHC). In addition to subtype markers (ASCL1, NEUROD1, POU2F3, and YAP1), the expression of nine cancer-specific proteins was evaluated.

The selected clinically relevant molecules showed no significant differences in their RNA expression profile when assessing the primary tumors and their corresponding LN metastases. Nevertheless, IHC analyses revealed significantly higher DLL3 expression in the primary tumors than in the LN metastases (P = 0.008). In contrast, NEUROD1 expression was significantly lower in the primary tumors (versus LN metastases, P < 0.001). No statistically significant difference was found by IHC analysis in the case of other clinically relevant proteins. Concerning SCLC molecular subtypes, a change in subtype distribution was detected in 21 cases. Phenotype switching from neuroendocrine (NE) subtypes toward non-NE lesions and from non-NE landscape toward NE subtypes were both detected.

Although the molecular landscape of SCLC LN metastases largely resembles that of the tumor of origin, key differences exist in terms of DLL3 and NEUROD1 expression, and in subtype distribution. These diagnostic pitfalls should be considered when establishing the tumors' molecular profile for future clinical trials solely based on LN biopsies.

Brain metastases (BM) portend increased morbidity and mortality in patients with small cell lung cancer (SCLC). We aimed to characterize the prevalence, timing, treatment patterns, and survival outcomes of BM associated with SCLC over the past decade.

Data from 4014 patients with histologically confirmed SCLC were extracted from the TriNetX Oncology database. Clinical and demographic variables were compared between patients with and without BM using Chi-squared and t-tests. Kaplan-Meier and Cox regression analyses were used to evaluate overall survival (OS), after propensity score matching cohorts for age at diagnosis, sex, cancer stage at diagnosis, extracranial metastases, and cancer-directed therapy.

Among 4014 patients with SCLC, 35.0% had BM (9.9% synchronous, 21.2% metachronous, 3.9% precocious). Patients who developed BM were younger (P < .001) at SCLC diagnosis, more likely Black/African American (P = .0068), and presented with more advanced cancer stages (P < .001) than patients who did not develop BM. The median BM-free survival from the time of SCLC diagnosis was 27.9 months. Patients with BM received higher rates of cancer-directed therapies than those without BM. Synchronous BM was associated with lower OS than metachronous BM after the diagnosis of SCLC (HR[95% CI] = 1.56[1.32-1.83]), but there was no difference in OS after the BM diagnosis. OS did not differ between patients with BM and patients with extracranial metastases only, following the diagnosis of metastatic disease.

Our findings support that independently of the chronicity of BM diagnosis, patients with SCLC have poor survival once the diagnosis of BM is conferred.

Positron emission tomography (PET) stands as the paramount clinical molecular imaging modality, especially in oncology. Unlike conventional anatomical-morphological imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI), PET provides detailed visualizations of internal activity at the molecular and cellular levels. 18-fluorine-fluorodeoxyglucose ([18F]FDG)-PET combined with contrast-enhanced CT (ceCT) significantly improves the detection of various cancers. Appropriate patient selection is crucial, and physicians should carefully assess the appropriateness of [18F]FDG-PET/CT based on specific clinical criteria and evidence. Due to its high diagnostic accuracy, [18F]FDG-PET/CT is indispensable for evaluating the extent of disease, staging, and restaging known malignancies, and assessing the response to therapy. PET/CT imaging offers significant advantages in patient management, particularly by identifying occult metastases that might otherwise go undetected. This can help prevent unnecessary surgeries, allowing many patients to be redirected to systemic chemotherapy instead. However, it is important to note that the gold standard for surgical planning remains CT and/or MRI, depending on the body region. These imaging modalities, with or without associated angiography, provide superior contrast and spatial resolution, essential for detailed surgical preparation and planning. [18F]FDG-PET/CT has a central role in the precise and early diagnosis of cancer, contributing significantly to personalized treatment plans. However, it has limitations, including non-tumor-specific uptake and the potential to inaccurately capture the metabolic activity of certain tumor types due to low uptake in some well-differentiated tumor cell lines. Therefore, it should be utilized in clinical scenarios where it offers crucial diagnostic insights not readily available with other imaging modalities. KEY POINTS: Use [18F]FDG-PET/CT selectively based on clinical appropriateness criteria and existing evidence to optimize resource utilization and minimize patient exposure. Employ [18F]FDG-PET/CT in treatment planning and monitoring, particularly for assessing chemotherapy or radiotherapy response in FDG-avid lymphoma and solid tumors. When available, [18F]FDG-PET/CT can be integrated with other diagnostic tools, such as MRI, to enhance overall diagnostic accuracy.

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid proliferation and high metastatic potential. It is characterized by universal inactivation of and RB1, overexpression of the MYC family and dysregulation of multiple oncogenic signaling pathways. Among different patients, SCLCs are similar at the genetic level but exhibit significant heterogeneity at the molecular level. The classification of SCLC has evolved from a simple neuroendocrine (NE)/non-neuroendocrine (non-NE) classification system to a transcription factor-based molecular subtype system; lineage plasticity adds further complexity and poses challenges for therapeutic development. While SCLC is initially sensitive to platinum-based chemotherapy, resistance develops rapidly, leading to a dismal prognosis. Various antibodies, including PD-1/PD-L1 inhibitors and antibody‒drug conjugates, have been introduced into clinical practice or are being evaluated in clinical trials. However, their therapeutic benefits for SCLC patients remain limited. This review summarizes SCLC carcinogenic mechanisms, tumor heterogeneity, and the immune microenvironment of SCLC, with a focus on recent advances in metastasis and resistance mechanisms. Additionally, the corresponding clinical progress in tackling these challenges is discussed.

Small cell bladder cancer (SCBC) is a rare histologic variant of bladder cancer with an aggressive disease course and poor outcomes. Given its uncommon nature, there is a paucity of high-quality data characterizing genomic drivers of this disease, and most patients are treated with approaches mirroring small cell lung cancer (SCLC). Leveraging the Tempus Lens deidentified clinically annotated genomic data set, we sought to evaluate the mutational landscape of SCBC relative to urothelial carcinoma (UC) and SCLC.

Somatic pathogenic genomic alterations in patients with SCBC, UC, and SCLC of any stage who underwent blood- or tissue-based genomic profiling through the Tempus assay were cataloged. Baseline clinical and demographic features were compared across histologic groups. Alterations were collated and summarized using descriptive statistics. Pairwise comparisons were performed to assess differences in mutation frequency across pathologic cohorts.

In total, 149 SCBC, 4,350 UC, and 1,697 SCLC patients were included in the study. The most common genomic alterations in SCBC were in TP53 (87%), TERT (75%), and RB1 (70%). Among SCBC patients with TP53 mutations, RB1 comutations were observed in 77% of patients. Compared with UC, SCBC patients were significantly enriched for TP53, RB1, KMT2D, and KDM6A mutations. Compared with SCLC, SCBC patients were enriched for TERT, ARID1A, and CREBBP mutations, among others (P < .05). Multiple clinically targetable mutations were observed in SCBC, including PIK3CA (19%), ERBB2/3 (13%), and ALK (10%). Limitations of this study include its retrospective nature.

This study represents one of the most extensive efforts to characterize SCBC to date, providing a novel understanding of the genomic alterations underlying the disease and revealing actionable mutations that could serve as potential targets for improved clinical outcomes.

This study aims to conduct a cost-effectiveness analysis of tislelizumab in combination with platinum and etoposide compared to the standard treatment of etoposide and platinum as first-line therapy for extensive-stage small cell lung cancer(ES-SCLC) from the Chinese medical system perspective.

A partitioned survival model was developed utilizing data from the RATIONALE-312 trial to accurately simulate the clinical and economic outcomes of both treatment arms. This model incorporates three distinct health states, namely progression-free survival, disease progression, and death. These states are exclusive of each other, and patients can transition between them as their disease progresses.The model accounted for various cost components such as drug therapy, management of adverse events, disease progression, and overall survival. To evaluate the cost-effectiveness of the interventions, quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) were chosen as the metrics. The analysis employed a willingness to pay (WTP) threshold of $39,855.79 per QALY. Additionally, sensitivity analyses were conducted to assess the robustness and reliability of the model.

The tislelizumab group had a total cost of $52,749.69, whereas the chemotherapy group's total expenses amounted to $8,811.62. Additionally, the tislelizumab group experienced a gain of 2.21 QALY compared to the chemotherapy group, albeit incurring an additional cost of $43,938.07. Consequently, this led to an ICER of $19,881.48, which falls below the Chinese WTP threshold of $39,855.79. Sensitivity analyses confirmed the robustness of the findings across a range of scenarios.

This cost-effectiveness analysis based on the RATIONALE-312 trial demonstrates that tislelizumab plus platinum and etoposide is a cost-effective treatment option for ES-SCLC compared to the standard chemotherapy from the Chinese medical system perspective.

Small cell lung cancer (SCLC) is a rapidly proliferating malignancy with a poor prognosis, commonly treated with concurrent chemoradiotherapy based on the etoposide and cisplatin (EP) regimen; however, this treatment is often complicated by febrile neutropenia (FN), a potentially life-threatening condition that can compromise treatment efficacy and patient safety. The aim of this study was to identify risk factors for FN in SCLC patients undergoing EP-based concurrent chemoradiotherapy to enhance treatment outcomes and improve patient management. In this retrospective case-control study, data from 216 SCLC patients who underwent concurrent chemoradiotherapy with the EP regimen between September 2014 and January 2020 were analyzed. Patients were categorized into FN (n = 106) and non-FN (n = 110) groups. Various clinical factors, including body mass index (BMI), Eastern Cooperative Oncology Group Performance Status (ECOG PS), and pre-treatment laboratory values such as albumin, IL-6, and C-reactive protein (CRP), were examined. Statistical analyses, including univariate and multivariate logistic regression, were performed to identify independent risk factors for FN. Lower BMI (P = 0.016) and poorer ECOG Performance Status (P = 0.001) were associated with an increased risk of FN. Additionally, pre-albumin levels (P = 0.010), inflammatory markers CRP (P = 0.032), and IL-6 (P = 0.001) also showed significant associations, suggesting that nutritional status and systemic inflammation play important roles in the development of FN. Importantly, multivariate logistic regression analysis confirmed pre-albumin levels (P = 0.003), IL-6 level (P = 0.001), MASCC score (P < 0.001), and ECOG PS (P = 0.019) as independent factors for FN risk. These findings highlight the importance of nutritional status, systemic inflammation, and overall health condition in predicting FN occurrence, underscoring the need for integrated risk assessment and management strategies to mitigate FN risk in SCLC patients undergoing EP-based concurrent chemoradiotherapy.

Procalcitonin (PCT) is a precursor of calcitonin, and its determination is used in daily clinical practice. It is a good marker for bacterial infection and can help diagnose sepsis. In this review, we summarize recent findings on the utility of PCT serum concentration measurement in noninfectious conditions. We found that elevated PCT levels may help in diagnosing or monitoring the course of cancer or inflammatory diseases. An increase was observed in emergency care such as acute renal failure or injuries, which may be promising in estimating the risk of complications. PCT has the potential to become a useful and clinically relevant marker beyond the assessment of bacterial infection. Due to its limited specificity, therapeutic decisions should be based on an individual evaluation of each clinical case.