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Objective: This study aims to assess the effectiveness of Short Stature Homeobox 2 (SHOX2) and RAS Association Domain Family 1 Isoform A (RASSF1A) gene methylation detection in residual liquid-based cytology (LBC) materials from Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) and investigate the diagnostic accuracy of a comprehensive diagnostic approach. Material and Methods: Between June 2022 and May 2023, a total of 110 cases that underwent EBUS-TBNA were enrolled in the study. SHOX2 and RASSF1A genes methylation detection using the residual cytological material, LBC, and cell block (CB) were conducted for each EBUS-TBNA case. The sensitivity and specificity of cytology, CB histopathology, SHOX2, and RASSF1A methylation in diagnosing EBUS-TBNA samples were determined based on follow-up data. Results: Among the 72 cases confirmed as pulmonary carcinomas, the methylation test yielded positive results in 24 adenocarcinoma cases, 10 squamous cell carcinoma cases, and 14 small cell carcinoma cases. The sensitivity of the comprehensive diagnosis (combining LBC, CB, and methylation detection) in distinguishing metastatic pulmonary epithelial malignancies in mediastinal and hilar lymph nodes or masses from benign lesions was higher (97.22%, 70/72) than that of morphological diagnosis alone (LBC and CB) (88.89%, 64/72; P < 0.05). Conclusion: SHOX2 and RASSF1A methylation detection demonstrates a high sensitivity and negative predictive value in the identification of pulmonary epithelial malignancies and holds promise as a valuable ancillary approach to enhance morphological diagnosis of EBUS-TBNA. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics of anti-neuronal antibody positive paraneoplastic neurological syndrome related to immune checkpoint inhibitors (ICI-PNS). Methods and Results A total of 5 patients with anti-neuronal antibody positive ICI-PNS in Peking Union Medical College Hospital from January 2012 to March 2024 were included. Tumor types included small cell lung cancer (2 cases), malignant melanoma (one case), Hodgkin lymphoma (one case) and cervical cancer (one case). Immune checkpoint inhibitors (ICIs) included programmed death 1 (PD-1) inhibitors (3 cases), programmed cell death ligand 1 (PD-L1) inhibitors (one case) and bispecific PD-1/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors (one case). All 5 patients presented with high-risk neurologic phenotypes of paraneoplastic neurological syndrome (PNS), of which 4 presented with limbic encephalitis and one presented with rapidly progressive cerebellar syndrome. Anti-neuronal antibodies detected in serum and/or cerebrospinal fluid of patients included anti-Hu, γ-aminobutyric acid receptor type B (GABABR), sex-determining region of Y chromosome-related high mobility group box 1 (SOX1), metabotropic glutamate receptor 5 (mGluR5) and Yo antibodies. Neurological syndromes occurred within 2 weeks after receiving ICIs in 4 patients. The modified Rankin Score (mRS) of 4 patients was 3 at peak of illness, and one patient was 5 at peak of illness. The Common Terminology Criteria for Adverse Events (CTCAE) was grade 3 in all 5 patients. After withdrawal of ICIs and treatment with glucocorticoids and intravenous immunoglobulin (IVIg), the neurological symptoms of the patients were improved. Conclusions High/intermediate-risk anti-neuronal antibodies are diagnostic markers of ICI-PNS. Evaluation of ICI-PNS clinical phenotypes and CTCAE grading are important for immunotherapy. Discontinuation of ICIs, administration of glucocorticoids and IVIg can improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

Small cell carcinoma (SCC) in the nasal cavity and sinuses is extremely rare. The clinical data of 15 patients with primary SCC in nasal cavity and sinuses were analyzed retrospectively. All patients were treated with surgery, radiotherapy, and chemotherapy. Of the 15 patients, 2 patients are alive for more than 6 years, and 5 patients died after the median follow-up period (11 months). Most of our patients represent the later stage (73% presented at stage III or IV) and had surgery combined with radiotherapy and chemotherapy; however, nearly half of patients have tumor recurrence and/or distant metastasis. SCC of nasal cavity and sinuses often invades surrounding tissues, and the long-term curative rate is generally low. Early diagnosis and comprehensive treatment are key to improve survival. Although the overall survival time of SCC is not optimistic, it is still recommended that patients take comprehensive treatment. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the outcomes of elderly patients with limited‐stage small cell lung cancer (LS‐SCLC), which may be linked to the timing of thoracic radiotherapy (TRT) following chemotherapy. Methods: Elderly patients (n = 78) with LS‐SCLC were divided into three groups depending on the timing of radiotherapy. The patients in the TRT group were stratified into early (TRT after 1–2 cycles of chemotherapy, n = 29), medium‐term (TRT after 3–4 cycles of chemotherapy, n = 33), and late (TRT after 5–6 cycles of chemotherapy, n = 16) TRT groups. The overall survival (OS) and progression‐free survival (PFS) were assessed and compared. Results: The medium‐term TRT group demonstrated significantly longer mPFS (20.12 months) and better mOS (35.97 months) than those in the other groups (PFS: P = 0.021;OS: P = 0.035). A pairwise comparison of the three groups revealed that those who received medium‐term TRT exhibited significantly improved PFS than the early (mPFS: 20.12 vs. 10.36 mouths, P = 0.018) and late (mPFS: 20.12 vs. 9.17 months, P = 0.016) TRT. The medium‐term TRT group demonstrated significantly improved OS than the early TRT (mOS: 35.97 vs. 25.22 months, P = 0.007) but not in comparison with the late TRT (mOS: 35.97 vs. 21.63 months, P = 0.100). Conclusion: In elderly patients with LS‐SCLC, the addition of TRT after 3–4 cycles of chemotherapy appears to be a viable and potentially beneficial treatment approach. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the primary cause of cancer-related deaths in China. This study analysed the incidence and survival trends of lung cancer from 2011 to 2020 in Fujian Province, southeast of China, and provided basis for formulating prevention and treatment strategies. Methods: The population-based cancer data was used to analyse the incidence of lung cancer between 2011 and 2020, which were stratified by sex, age and histology. The change of incidence trend was analysed using Joinpoint regression. The relative survival of lung cancer with onset in 2011–2014, 2015–2017 and 2018–2020 were calculated using the cohort, complete and period methods, respectively. Results: There were 23,043 patients diagnosed with lung cancer in seven registries between 2011 and 2020, with an age-standardized incidence rate (ASIR) of 37.7/100,000. The males ASIR increased from 51.1/100,000 to 60.5/100,000 with an annual percentage change (APC) of 1.5%. However, females ASIR increased faster than males, with an APC of 5.7% in 2011–2017 and 21.0% in 2017–2020. Compared with 2011, the average onset age of males and females in 2020 was 1.5 years and 5.9 years earlier, respectively. Moreover, the proportion of adenocarcinoma has increased, while squamous cell carcinoma and small cell carcinoma have decreased over the past decade. The 5-year relative survival of lung cancer increased from 13.8 to 23.7%, with a greater average increase in females than males (8.7% and 2.6%). The 5-year relative survival of adenocarcinoma, squamous cell carcinoma and small cell carcinoma reached 47.1%, 18.3% and 6.9% in 2018–2020, respectively. Conclusions: The incidence of lung cancer in Fujian Province is on the rise, with a significant rise in adenocarcinoma, a younger age of onset and the possibility of overdiagnosis. Thus, Fujian Province should strengthen the prevention and control of lung cancer, giving more attention to the prevention and treatment of lung cancer in females and young populations. [ABSTRACT FROM AUTHOR]

Small cell carcinoma of the cervix is a rare but poor prognosis pathological type of cervical cancer, for which advice in clinical guidelines is unspecific. We therefore aimed to investigate the factors and treatment methods that affect the prognosis of patients with small cell carcinoma of the cervix. In this retrospective study, we collected data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries cohort and a Chinese multi-institutional registry. The SEER cohort included females diagnosed with small cell carcinoma of the cervix between Jan 1, 2000, and Dec 31, 2018, whereas the Chinese cohort included women diagnosed between Jun 1, 2006, and April 30, 2022. In both cohorts, eligibility was limited to female patients older than 20 years with a confirmed diagnosis of small cell carcinoma of the cervix. Participants who were lost to follow-up or those for whom small cell carcinoma of the cervix was not the primary malignant tumour were excluded from the multi-institutional registry, and those with an unknown surgery status (in addition to those for whom small cell carcinoma of the cervix was not the primary malignant tumour) were excluded from the SEER data. The primary outcome of this study was overall survival (length of time from the date of first diagnosis until the date of death from any cause, or the last follow-up). Kaplan-Meier analysis, propensity score matching, and Cox-regression analyses were used to assess treatment outcomes and risk factors. 1288 participants were included in the study; 610 in the SEER cohort and 678 in the Chinese cohort. Both univariable and multivariable Cox regression analysis (SEER hazard ratio [HR] 0·65 [95% CI 0·48–0·88], p=0·0058; China HR 0·53 [0·37–0·76], p=0·0005) showed that surgery was associated with a better prognosis. In subgroup analyses, surgery remained a protective factor for patients with locally advanced disease in both cohorts (SEER HR 0·61 [95% CI 0·39–0·94], p=0·024; China HR 0·59 [0·37–0·95]; p=0·029). Furthermore, the protective effect of surgery was observed among patients with locally advanced disease after propensity score matching in the SEER cohort (HR 0·52 [95% CI 0·32–0·84]; p=0·0077). In the China registry, surgery was associated with better outcomes in patients with stage IB3-IIA2 cancer (HR 0·17 [95% CI 0·05–0·50]; p=0·0015). This study provides evidence that surgery improves outcomes of patients with small cell carcinoma of the cervix. Although guidelines recommend non-surgical methods as first-line treatment, patients with locally advanced disease or stage IB3-IIA2 cancer might benefit from surgery. The National Key R&D Program of China and the National Natural Science Foundation of China. [ABSTRACT FROM AUTHOR]

Objectives: Our research aimed to evaluate the effectiveness of first‐line immune checkpoint inhibitors (ICIs) with etoposide and platinum (EP) for extensive‐stage small cell lung cancer (ES‐SCLC) and identify prognostic factors, as real‐world outcomes and the inconsistency of PD‐1 and PD‐L1 inhibitors are uncertain. Methods: We selected ES‐SCLC patients in three centers and conducted a propensity score‐matched analysis. The Kaplan–Meier method and Cox proportional hazards regression were conducted to compare the survival outcomes. We also performed univariate and multivariate Cox regression analyses to investigate predictors. Results: Among 236 patients included, 83 pairs of cases were matched. The EP plus ICIs cohort had a longer median overall survival (OS) (17.3 months) than the EP cohort (13.4 months) (hazard ratio [HR], 0.61 [0.45, 0.83]; p = 0.001). The median progression‐free survival (PFS) was also longer in the EP plus ICIs cohort (8.3 months) than in the EP cohort (5.9 months) (HR, 0.44 [0.32, 0.60]; p < 0.001). The EP plus ICIs group had a higher objective response rate (ORR) (EP: 62.3%, EP + ICIs: 84.3%, p < 0.001). Multivariate analysis presented that liver metastases (HR, 2.08; p = 0.018) and lymphocyte–monocyte ratio (LMR) (HR, 0.54; p = 0.049) were independent prognostic factors for OS, and performance status (PS) (HR, 2.11; p = 0.015), liver metastases (HR, 2.64; p = 0.002), and neutrophil‐lymphocyte ratio (NLR) (HR, 0.45; p = 0.028) were for PFS in patients with chemo‐immunotherapy. Conclusion: Our real‐world data demonstrated that ICIs with chemotherapy as the first‐line setting for ES‐SCLC are effective and safe. PS, liver metastases, and inflammatory markers could serve as valuable risk factors. [ABSTRACT FROM AUTHOR]

Small cell carcinoma of the bladder (SCCB) is a rare, highly malignant neuroendocrine tumor. This study attempted to analyze tumor characteristics, treatments and clinical outcomes in China. We conducted a retrospective analysis of patients diagnosed with non-metastatic SCCB at multi-institutions between January 2007 and January 2022. The Kaplan-Meier method was used to calculate survival. A total of 20 patients were included. 10 had localized disease (T1-2N0), and 10 had locally advanced disease (≥ T3 or N+). 13 received local treatment (partial cystectomy or transurethral resection of the bladder tumor) and 7 received radical treatment (radical cystectomy or radiotherapy). A total of 18 patients (90%) received chemotherapy (CT), either neoadjuvant CT (n = 5) or adjuvant CT (n = 13). The median OS for the receiving local treatment was 65.3 months (95% CI 0 to 138 months) and the corresponding 1-year, 2-year, and 3-year OS was 77%, 54%, and 54%, respectively. The median OS for the receiving radical treatment was not reached and the corresponding 1-year, 2-year, and 3-year OS was 100%, 100%, and 75%, respectively. The median PFS for receiving local treatment was 13.8 months (95% CI 9.3 to 18.3 months) and the corresponding 1-year, 2-year, and 3-year PFS was 46%, 31%, and 31%, respectively. The median PFS for the receiving radical treatment was not reached and the corresponding 1-year, 2-year, and 3-year PFS was 83%, 56%, and 56%, respectively. This study reported the largest cohort of non-metastatic SCCB among Chinese population. Given its metastatic potential, CT remained an essential part of the treatment. The survival outcomes of radical cystectomy and RT in non-metastatic SCCB were encouraging., (© 2024. The Author(s).)

Objective: Small cell lung cancer (SCLC) is one of the most aggressive malignancies characterized by neuroendocrine (NE) differentiation. The Delta‐like protein 3 (DLL3), as a direct downstream target of ASCL1, is involved in NE differentiation and carcinogenesis of SCLC. This study aims to investigate the relationship between ASCL1 and DLL3 expressions and their clinicopathological implications in SCLC. Methods: A total of 247 surgically resected pure SCLC samples with limited clinical stage and follow‐up data were retrieved in this retrospective study. ASCL1 and DLL3 protein expression was detected by immunohistochemistry staining. The correlations between ASCL1 and DLL3 expressions, as well as their clinicopathological features, were analyzed by χ2 tests. Disease‐free survival (DFS) and overall survival (OS) in SCLC patients with ASCL1/DLL3 low and high expressions were compared by the Kaplan‐Meier method and log‐rank tests. Results: ASCL1 high expression was detected in 105 (42.5%) patients. Its expression was positively correlated with the clinical stage (p = 0.02) and nerve invasion (p = 0.03). DLL3 high expression was observed in 188 (72.8%) patients and was correlated with vascular invasion (p = 0.04). ASCL1 expression was positively associated with DLL3 expression (p = 0.03). In addition, DLL3 expression has a strong correlation with the expression of thyroid transcription factor‐1 (TTF1) and conventional NE markers. Conclusion: ASCL1 and DLL3 were highly expressed in SCLC tumor samples, and a positive correlation between these two markers was observed. Co‐analysis of ASCL1 and DLL3 may identify a distinct SCLC subgroup benefit from targeted therapy. Therefore, ASCL1 and DLL3 could be potential biomarkers served for the selection of related patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature., Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies., Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4-120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens., Conclusion: This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: Extensive‐stage small cell lung cancer (ES‐SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES‐SCLC since 2018, ES‐SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES‐SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES‐SCLC population. Methods: We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from January 1, 2011 to December 31, 2018 in a Chinese top‐level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis. Results: The median overall survival (OS) of ES‐SCLC patients (N = 358) was 14.0 months, the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR < 76) as independent prognostic factors for OS in this patient population. Progression‐free survival (PFS) data of 238 patients was obtained for further analysis, and the median PFS was 6.2 months, and six‐month and one‐year PFS rates were 51.7% and 14.3%, respectively. Elevated cyfra211, decreased Hb and Na were identified as independent prognostic factors for PFS. Conclusions: This study provides real‐world evidence of the survival and prognosis of ES‐SCLC patients which will enable better evaluation and clinical decision‐making in the future. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) is characterized by aggressive spread and poor prognosis, but has limited treatment options. Results of prognostic factors from randomized trials on treatment arrangement are conflicting and large‐scale real‐world analysis is lacking. Methods: Patients diagnosed SCLC between 2008 and 2018 in Peking University Cancer Hospital were included in this study. Kaplan–Meier methods were adopted, and univariate analysis and multivariate Cox regression models were constructed to analyze prognostic factors. Results: Among 1045 patients who presented to our center, 988 eligible patients were identified. Median overall survival (OS) was 16.0 months for the whole group, 24.0 months and 11.0 months for limited stage small cell lung cancer (LS‐SCLC) and extensive stage small cell lung cancer (ES‐SCLC), separately. Limited‐stage, good performance status (PS) (ECOG 0–1), response to primary systemic treatment, and patients who received initiative irradiation and three or more lines of chemotherapy were predicted to have better OS in the whole group. Only response to first‐line systemic therapy and prophylactic cranial irradiation (PCI) were independent prognostic factors of survival in LS‐SCLC; while good PS (ECOG 0–1), without liver, bone, or subcutaneous metastases, response to first‐line therapy, initial local irradiation, and three or more lines of systemic therapy predicted a favorable prognosis in ES‐SCLC. Conclusions: The present study retrieved from large real–world data suggested that response to primary systemic therapy and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS‐SCLC and ES‐SCLC, respectively. [ABSTRACT FROM AUTHOR]

• The most common mutations identified were TP53 and RB1 in transformation to SCLC. • The rates of RB1 and TP53 were similar between first and third-generation TKI treatment. • Earlier occurrence of SCLC transformation was associated with poorer prognosis. • Anlotinib may be a good treatment choice in transformation to SCLC population. Transformation to small cell lung cancer (SCLC) is a resistance mechanism to tyrosine kinase inhibitor (TKI) treatment that develops in lung adenocarcinoma. The genomic and treatment outcomes in these populations have not been comprehensively reported in China. We performed a retrospective study analyzing patients with advanced non-SCLC (NSCLC) from eight sites who were diagnosed with SCLC transformation after receiving epidermal growth factor receptor (EGFR)-TKI treatment including first/second- or third-generation EGFR-TKIs. We assessed the genomic features and clinical prognosis in these patients with EGFR-mutated lung cancer. Thirty-two eligible patients with EGFR mutations were identified, 25 of whom had sufficient tumor tissues for detection of genes by next-generation sequencing. The median progression free survival (mPFS) for first/second-generation TKIs was 14.0 months. The most common mutations identified in samples with transformation to SCLC were in TP53 (17/25, 68.0 %), RB1 (9/25, 36.0 %), and PIK3CA (3/25, 12.0 %), and the incidence rates of RB1 and TP53 mutations were similar between patients receiving first/second-generation and third-generation TKI treatment. The estimated median time to SCLC transformation was 17.0 months. After SCLC transformation, platinum-etoposide was the most common treatment regimen, and the mPFS after platinum-etoposide treatment was 3.5 months. Anlotinib showed good efficacy in these patients (overall response rate, 66.7 %; mPFS, 6.2 months). The median overall survival after the initial diagnosis of metastatic lung cancer was 34.5 months, and patients with small cell transformation after third-generation TKI treatment had better prognosis than patients with transformation after first/second-generation treatment (49.4 months vs. 20.0 months, P = 0.013). We observed that TP53 and RB1 mutations were common in Chinese patients with SCLC transformation, regardless of whether first/second-generation or third-generation EGFR-TKI treatments were used. Earlier occurrence of small cell transformation after EGFR-TKI treatment was associated with poorer prognosis of patients. After the standard chemotherapy regimens for the management of primary SCLC, anlotinib may be a therapeutic option. [ABSTRACT FROM AUTHOR]

The purpose was to compare the treatment outcomes of radical chemoradiotherapy versus radical surgery plus adjuvant chemotherapy or chemoradiotherapy in locally advanced primary small cell carcinoma of the esophagus (LA-PSCCE). The hypothesis was that radical chemoradiotherapy had better overall survival (OS) than radical surgery plus adjuvant chemotherapy or chemoradiotherapy. This large-scale multicenter retrospective study in China enrolled patients with newly diagnosed LA-PSCCE (T3-4N0M0 or TanyN+M0, AJCC 8th edition) from 2008 to 2021. According to different curative treatment approaches, patients were divided into two groups: radical chemoradiotherapy (group: CRT), and radical surgery following adjuvant chemotherapy or chemoradiotherapy (group: S + CT/CRT). The propensity score match (PSM) was applied to reduce the effect of confounding biases in clinicopathological characteristics (age, gender, KPS, tumor location, tumor length, and cTNM stage). Univariate Cox-regression analysis and Kaplan-Meier curve were calculated for OS. Statistical results were summarized as hazard ratio (HR), 95% confidence interval (CI) and P value. A two-sided P < 0.05 was regarded to be statistically significant. A total of 291 patients with a median follow-up of 4.3 years were retrospectively enrolled. After PSM analysis, 94 and 94 patients were eventually included in group CRT and S + CT/CRT, respectively. Group CRT demonstrated a significantly superior survival than group S + CT/CRT (HR, 0.63; 95% CI, 0.43-0.91; P = 0.01), with a 3-year OS of 49.5% and 27.8% (P = 0.02), respectively. In secondary analysis, patients treated with radical chemoradiotherapy consistently showed significant survival benefit than those with radical surgery plus adjuvant chemoradiotherapy (HR, 0.4; 95% CI, 0.21-0.79; P = 0.008). For patients with newly diagnosed LA-PSCCE, radical chemoradiotherapy should be a preferred recommendation in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the leading cause of morbidity and mortality worldwide. Small cell lung cancer (SCLC) has been determined to be the most lethal lung malignancy. Few studies have previously analyzed the epidemiological characteristics of SCLC in China. This study analyzed the epidemiological characteristics of SCLC aiming to provide a reference for the prevention of SCLC in Hebei Province. Methods: The epidemiological characteristics of SCLC using lung cancer data based on population and hospital cancer registries in Hebei Province between 2008 and 2017 were analyzed. Results: The proportion of both population‐ and hospital‐based SCLC cases displayed a significant increasing trend. Moreover, the proportion of males was higher than that for female based on population‐ and hospital‐based cases. The proportion of hospital‐based SCLC cases in counties was higher than that in cities, whereas there were no significant regional differences between cities and counties based on population. The proportion of both population‐ and hospital‐based SCLC cases decreased consistently with increasing age. There was a difference between population‐ and hospital‐based distribution of subcategories of SCLC. Conclusions: Significant increases in the proportion of both population‐ and hospital‐based SCLC cases over recent years, particularly in males and in patients aged over 55 years, were observed. Research on the pathogenesis of SCLC in these patients and prevention is urgently required. [ABSTRACT FROM AUTHOR]

Background and objective As a new technique developed in recent years, endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has the advantages of simple operation, minimal invasive, high accuracy, safety and repeatability. It has become a new standard for lung cancer diagnosis and mediastinal staging. Because small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) have different biological characteristics and treatment methods, it is very important to diagnose and differentiate the types of lung cancer in the early stage of lung cancer for the staging, treatment and prognosis of lung cancer. This article evaluated the accuracy and sensitivity of EBUS-TBNA in the diagnosis of SCLC and NSCLC. Methods From January 2012 to December 2018, the clinical data of 85 patients with SCLC and NSCLC who performed EBUS-TBNA in Xuan Wu Hospital CMU were retrospectively analyzed and the differences between the two groups were compared. Results 45 cases of SCLC were confirmed by immunohistochemistry and pathology. 42 cases of SCLC were diagnosed by EBUS-TBNA. The accuracy and sensitivity of diagnosis were 93.3% (42/45) and 100.0% (42/42), respectively. The positive rate of diagnosis was 48.9% (22/45) in 22 cases diagnosed by cytology, and 40 cases diagnosed by pathology, including 35 cases diagnosed by EBUS-TBNA. The accuracy and sensitivity of diagnosis were 87.5% (35/40) and 100.0% (35/35), respectively. The positive rate of diagnosis was 27.5% (11/40) in 11 cases diagnosed by cytology. The diagnostic sensitivity of EBUS-TBNA in SCLC group was significantly higher than that in NSCLC group (P<0.05). Conclusion EBUS TBNA is more sensitive in the diagnosis of SCLC than NSCLC. As a minimally invasive technique, EBUS-TBNA can assist SCLC in early diagnosis and timely treatment. [ABSTRACT FROM AUTHOR]

Purpose. Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. Materials and Methods. Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. Results. A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. Conclusion. TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the leading cause of cancer mortality among women in China, and incidence and mortality continue to rise despite the fact that smoking prevalence is very low among Chinese women. Aim: This study investigated tobacco smoking and trends in histological subtypes of female lung cancer in a central cancer hospital in China. Methods: Demographic, smoking history and histological information on female lung cancer patients diagnosed or treated from 2000 to 2012 was collected from the Cancer Hospital, Chinese Academy of Medical Science (CHCAMS). The classification of histological subtypes and clinical stages were conducted using the ICD‐O‐3 and Eighth AJCC Cancer Staging Manuals. Time‐trends of histological subtypes were analyzed based on annual percentage change (APC). Results: Overall, 5870 female cases of lung cancer were included in the analysis. The number of female lung cancer patients increased from 509 (2000–2002) to 1744 (2011–2012). The most common histological type of lung cancer was adenocarcinoma (ADC) (72.93%), followed by small cell lung cancer (SCLC) (11.06%), squamous cell carcinoma (SCC) (8.38%) and other (7.63%). Among smokers, the proportion of SCC decreased from 40.5% to 23.7% (P = 0.005), while ADC increased from 35.7% to 50.7% (P = 0.009). In non‐smokers, ADC increased from 63.1% to 80.6% (P = 0.006) and SCC decreased from 13.6% to 4.5% (P = 0.016). Among SCC cases, smokers made up a larger proportion of early stage (I/II: 47.1%) compared with late stages (III, 34.3%; IV, 18.6%). Conclusion: The number of female lung cancer patients has increased in CHCAMS. In both smoking and non‐smoking cases, the proportion of adenocarcinoma increased. Squamous cell carcinomas were more likely to be diagnosed in early stages among smokers. [ABSTRACT FROM AUTHOR]

Background: The optimal standard treatment for primary small cell carcinoma of the esophagus (SCCE) remains undetermined. In this study, we conducted two areas of research on SCCE. First, we analyzed differences in SCCE characteristics between Chinese and U.S. patients. Second, we evaluated optimal treatment strategies for SCCE in the Chinese cohort. Methods: Data from 137 Chinese SCCE patients collected from two cancer centers in China were compared with 385 SCCE patients registered in the U.S. SEER program. Prognostic factors were further analyzed in the Chinese group. Propensity score matching (PSM) was used to balance baseline features between the groups. Results: There were more Chinese SCCE patients with regional stage disease (41.6%) and surgery was the principal local therapy (78.1%), while 51.7% of U.S. patients was at advanced stages and tended to receive radiotherapy as the main therapy (45.2%). Median overall survival (MST) of Chinese patients was 15.0 months, compared with 8.0 months for U.S. patients (P < 0.001). However, the survival differences between groups disappeared after PSM (MST: 12.5 m vs 9.0 m, P = 0.144). Further analysis found that surgery tended to achieve clinical benefits only for patients with localized disease (T1‐4aN0M0). Radiotherapy and chemotherapy may prolong survival in patients with regional and extensive disease. Conclusions: Although there are huge differences in the tumor characteristics and treatment modalities of SCCE between Chinese and U.S. patients, the prognosis of SCCE is equally poor in both. Surgery should be considered for patients with localized disease, while chemoradiotherapy is recommended for patients with regional and extensive disease. Although there are huge differences in the tumor characteristics and treatment modalities of SCCE between Chinese and U.S. patients, the prognosis of SCCE is equally poor in both. Surgery should be considered for patients with localized disease, while chemoradiotherapy is recommended for patients with regional and extensive disease. This study will be helpful to guide the treatment of SCCE in the future. [ABSTRACT FROM AUTHOR]

Small cell carcinoma of the esophagus (SCCE) is a rare type of esophageal cancer, the incidence of it is only 0.1% to 2.4% in all cases of esophageal cancer. However, the optimal disease staging system has not yet been defined. To comprehensively explore the impact of AJCC TNM Staging 8th edition on survival outcome of SCCE. From January 2007 to December 2020, 909 patients with SCCE who had completed TNM staging from 14 cancer centers in China were retrospectively examined. Univariate survival rate analyses were estimated using the Kaplan and Meier method, with comparisons made between groups by the log-rank test. All statistical analyses were conducted using SPSS 25 statistical software. Statistical significance was assumed for a two-tailed p value less than 0.05. TNM stage also was a statistically significant prognostic factor for OS and PFS in SCCE(p<0.001). Increasing clinical T category using the AJCC8 TNM staging system resulted in progressively poorer survival in patients who did not have metastatic (M0) involvement(p<0.01). However, the results of pairwise comparisons showed no significant differences in survival between patients with adjacent phases except for those between T3 versus T2 (p<0.0001). N staging also showed significant influence on OS, and with significant difference between successive stages (p<0.05) except that between the survival rates of N1 and N2 cases (p = 0.00758). Similar to t category, increasing M category was associated with progressively worse survival. The T and N staging confirmed significant influence on PFS in the SCCE patients (p<0.001). AJCC TNM Staging 8th edition criteria for SCCE patients has a high prognostic impact. Therefore, it is applied to clinical practice and future therapeutic trials. [ABSTRACT FROM AUTHOR]

Background: In recent years, lung cancer incidence has been increasing; however the impact of different histological types of lung cancer is not yet clear. Methods: Trends in the lung cancer incidence rate by histological type were examined based on data of 36 658 primary lung cancer patients from West China Hospital between 1995 and 2015. Results: The most common histological type of lung cancer in our hospital was adenocarcinoma (ADC) in both genders, followed by squamous cell carcinoma (SQCC), and small cell carcinoma (SCLC), which is consistent with general worldwide trends. The proportion of young patients with SCLC showed a downward trend. In the overall population with lung cancer, the number of elderly patients with lung cancer increased significantly, while the proportion of elderly patients increased gradually. The mean age at diagnosis also increased. The number of women with ADC increased sharply in recent years, especially in young patients, and the incidence rate in women is now greater than in men. Conclusion: Significant increases in the number of patients with ADC and the rate of lung cancer in women over recent years were observed, indicating that research on the pathogenesis of disease in these patients is urgent. [ABSTRACT FROM AUTHOR]

Background: At present, it has not yet been determined whether metastasis can be transferred cross‐lobe to peripheral lymph nodes (LNs) from other lobes in early stages of lung cancer, especially without any direct involvement to the pleura and parenchyma of the lobe. This study was conducted to investigate this issue. Methods: A retrospective analysis was conducted at the Chinese Academy of Medical Sciences. Patients undergoing right middle and lower lobectomy with lymphadenectomy for preoperative clinical stage Ia–IIIa from 2014 to 2015 were identified. To avoid interference, cases were limited to tumors within the primary lobe. When a tumor is completely located in the lower lobe, no direct invasion occurs into the visceral pleura/bronchus/parenchyma of the middle lobe and tumor cell metastasis into the peripheral LNs (stations 12–14) in the middle lobe is defined as cross‐lobe lymph node metastasis (CLM). Results: A total of 68 patients were identified, of which nine (13.2%) had CLM. Seven had squamous cell carcinoma, one adenocarcinoma, and one small cell carcinoma. Seven cases (77.8%) had intermediate bronchus invasion, and seven cases (77.8%) intermediate bronchus adjacent lymph node involvement (station 11). Compared to non‐CLM patients, tumor diameter (5.2 vs. 3.2; P = 0.28), N2 lymph node metastasis rate (66.7% vs. 28.8%; P = 0.03), late stage (IIIa 77.8% vs. 35.6%; P = 0.04), and invasion of intermediate bronchus (77.8% vs. 45.8%; P = 0.07) relatively increased. Conclusion: Non‐primary lobe peripheral LN metastasis exists in lung cancer and requires greater attention and further study. [ABSTRACT FROM AUTHOR]

Primary small cell carcinoma of the esophagus (PSCCE) is a rare and highly malignant disease that carries a poor prognosis. The optimal treatment strategies for limited-stage PSCCE have not been established. We retrospectively reviewed the clinical records of limited-stage PSCCE patients who received chemotherapy (CT) or chemotherapy-based combined modality therapy (CMT) between December 2000 and December 2020 from the 15 hospitals in China. Patients were divided into the following two groups according to the treatment strategies: the CT group and the CMT group. A 1:3 propensity score matching (PSM) approach was applied to balance observable potential confounding factors between the two groups. The primary endpoint was overall survival (OS). A total of 544 patients were enrolled in our study, including 84 patients in the CT group and 460 patients in the CMT group. Univariate analysis and multivariate analysis found that Eastern Cooperative Oncology Group classification, primary tumor length, TNM stage, number of chemotherapy cycles, and treatment strategies were the independent predictors of OS. The 3-year rate of brain metastasis was 11.1% in the CMT group. After PSM, the patients' characteristics between the CT group (n=82) and the CMT group (n=218) were well balanced. The median OS in the CT and CMT group was 17.34 and 24.60 months, respectively, and the difference was statistically significant (P < 0.001). Moreover, progression-free survival (PFS), locoregional PFS, and distant PFS were also significantly different between the two groups (P < 0.05). Compared with CT, chemotherapy-based CMT may improve OS and PFS and was the optimal treatment strategy for limited-stage PSCCE. On the other hand, prophylactic brain irradiation is not recommended. [ABSTRACT FROM AUTHOR]

The rarity of primary small cell carcinoma of the esophagus (PSCE) has limited the clinical feature and survival analysis with large sample size. Tissue chromogranin A (CgA) protein expression has been reported to be a useful biomarker for diagnosing PSCE. Interestingly, recent studies have indicated tissue CgA as a significant prognostic marker in multiple human cancers, but without PSCE. The present study, thus, was undertaken to characterize the clinicopathological changes and to evaluate the associations of tissue CgA expression with clinical response on Chinese PSCE patients. All the 125 PSCE patients were enrolled from our 500,000 esophageal and gastric cardia carcinoma databases (1973-2015), constructed by the cooperative team from more than 700 hospitals in China and established by Henan Key Laboratory for Esophageal Cancer Research in Henan, China. Immunostaining for CgA showed that CgA was mainly located in cytoplasm of tumor cells with a positive detection rate of 44.6%. The CgA positive expression rate in PSCE at lower segment of the esophagus (72.2%) was higher than that at middle segment (41.5%) (P = 0.001). However, CgA protein expression did not correlated with lymph node metastasis (P = 0.767), TNM staging (P = 0.740), tumor invasion (P = 0.253), gender (P = 0.262), and age (P = 0.250). Multivariate survival analysis showed that the patients with higher CgA protein expression had a superior long survival than those without CgA expression (P = 0.037). The clinicopathological analysis showed that PSCE occurred predominantly in male (M:F = 1.9:1) at the middle segment (68%) of the esophagus. Histologically, 89.6% were pure PSCE and 10.4% were mixed type with either squamous cell carcinoma (8%) or adenocarcinoma (2.4%). It was noteworthy that, with the in-depth invasion from T1 to T2 and T3, the positive lymph node metastasis rate increased dramatically from 38%, 56% to 74%, respectively. The survival rates of 1-, 2-, 3-, and 5-year were 64%, 35%, 18%, and 7%, respectively. The Kaplan-Meier survival analysis showed that the young patients (≤60 years) had longer survival than the elderly (P = 0.011). Interestingly, multivariate survival analysis revealed that the patients with mixed PSCE had a significantly better survival than those with pure PSCE (P = 0.015). Furthermore, the median survival time for the patients with and without lymph node metastasis was 1.16 and 2.03 years, respectively. But, the difference was not significant (P = 0.143). Univariate analysis did not show any survival influence by gender, tumor location, tumor invasion depth, and TNM staging. It was noteworthy that, of the 13 early PSCE patients (T1N0M0), only one patient had more than 5 year survival, the others died with less than one or two year (65%). The present study indicates that the PSCE is of badly worsen prognosis, even in the pathological early stage. Tissue CgA protein expression is a promising maker not only for diagnosis and also for prognosis. Further assessment is needed to establish specific PSCE pathological staging system and to clarify the mechanisms of CgA protein in PSCE progression and prognosis. [ABSTRACT FROM AUTHOR]

Background and objective Eye is a rare site of lung cancer metastasis, and ocular metastasis is one of the largest challenges to cancer patients' quality of life (QOL). Here we present our experience on ocular metastasis of lung cancer and review relevant literature in an attempt to investigate the clinical features, treatment, and prognosis of these tumors. Methods The records of 9 patients with ocular metastasis of lung cancer treated at our hospital were analyzed. A literature review identified 42 cases reported in the last 10 years and their medical records were retrospectively estimated. Results The median age of our patients was 51 years (range 41-61). Diagnosis of lung cancer included non-small cell lung carcinoma (NSCLC) in 7 patients, in which adenocarcinoma (ADC) were recorded in 6 patients, small cell lung carcinoma (SCLC) in 1 patient, and unknown in 1 patient. The site of ocular metastasis included choroid (n=8) and iris (n=1). In the literature review, SCLC con- stituted 21.4% (n=9) and ADC constituted 47.6% (n=20). Choroid presented to be the most common site for eye metastasis (66.7%, n=28). As for disease control rate, systemic chemotherapy for lung cancer patients with ocular metastasis presented to be only 28%. Meanwhile, combination of systemic treatment with ocular treatment could improve patients' eye symptoms effectively. Conclusion The most common lung cancer that metastasizes to the eye is ADC. The choroid is the most common site for ocular metastasis. Ocular treatment can improve patients' eye symptoms, while the effect of systemic chemotherapy treatment is limited. [ABSTRACT FROM AUTHOR]

In order to study the pattern of lymph node metastases after esophagectomy of small cell carcinoma of the esophagus (SCCE) and clarify the clinical target volume (CTV) delineation of definite radiotherapy for SCCE. From January 2007 to December 2020, 286 patients with SCCE who had undergone esophagectomy and lymphadenectomy were retrospectively examined from 14 cancer centers in China. The distribution of lymph node metastases was evaluated and the clinicopathologic factors related to lymph node metastasis were analyzed using logistic regression analysis. 177 patients (61.9%) occurred lymph node metastases in the 286 patients, including 1 positive lymph node (n=58), 2 positive lymph nodes (n=32), 3 positive lymph nodes (n=32) and more than 4 positive lymph nodes (n=55). The mean number of dissected lymph nodes was 17.0, with a rage of 7-60. The incidence of lymph node metastasis was 12.3% (597/4850). The rates of lymph node metastases in patients with upper thoracic tumors were 0% cervical, 32.1% (9/28) upper mediastinal, 7.1% (2/28) middle mediastinal, 0% lower mediastinal, 3.6% (1/28) abdominal, respectively. The rates of lymph node metastases in patients with middle thoracic tumors were 4.3% (6/139), 20.9% (29/139) , 26.6% (37/139) , 2.9% (4/139) , 25.9% (36/139), respectively. The rates of lymph node metastases in patients with lower thoracic tumors were 0%, 12.6% (15/119) , 41.2% (49/119) , 5.0% (6/119) , 47.9% (57/119), respectively. T stage and the length of tumor were the statistically significant risk factors of lymph node metastases of SCCE (P <0.05). To our known, this is a first study about investigating the pattern of lymph node metastases after esophagectomy and guiding the CTV delineation of definite radiotherapy for SCCE. Regardless of tumor location, the upper middle mediastinum is high incidence area of lymph node metastases, abdominal is also high incidence area of lymph node metastases for middle and lower thoracic tumors. The rate of lymph node metastasis of the SCCE increased with the T stage and the length of tumor. These factors and the correlated lymphatic drainage regions should be considered when designing the CTV for Selective regional irradiation of SCCE. [ABSTRACT FROM AUTHOR]

Background To investigate whether the response to induction chemotherapy ( IC) would impact the timing of thoracic radiotherapy ( TRT) in limited-stage small-cell lung cancer ( LS-SCLC). Methods A total of 146 patients with LS-SCLC who had received two to six cycles of IC followed by TRT from January 2009 to December 2011 at our hospital were included in this study. Patients were divided into two groups based on the time TRT was administered: early TRT (administered after 2-3 cycles of chemotherapy) or late TRT (administered after 4-6 cycles). Overall survival ( OS) and progression-free survival ( PFS) were analyzed using the Kaplan- Meier method. Multivariate Cox regression analysis was performed to evaluate the independent factors affecting survival. Results The median OS for patients who received early TRT and late TRT was 29.0 and 19.9 months, respectively, ( P = 0.018) and the median PFS was 18.5 and 13.8 months, respectively ( P = 0.049). In patients who achieved complete remission ( CR) or partial remission ( PR) after two to three cycles of IC, the median OS was 36.1 and 22.5 months in the early and late TRT subgroups, respectively ( P = 0.009); the corresponding median PFS was 20.2 and 13.8 months, respectively ( P = 0.038). In the patients who did not achieve CR or PR, no statistic difference was found in OS or PFS between the two subgroups. Conclusion Patients who received early TRT had more favorable outcomes than those who received late TRT. Patients who achieved CR or PR after two to three cycles of IC obtained more benefit from early TRT. [ABSTRACT FROM AUTHOR]

Background This study was designed to compare toxicities, disease control, and survival outcomes for limited disease small-cell lung cancer ( LD-SCLC) treated with once daily ( QD) versus twice daily ( BID) radiotherapy. Methods All of the patients received four to six cycles of platinum plus etoposide. In the QD group, irradiation was given via conventional radiotherapy with a dose of 60 Gy at 2 Gy per once-daily fraction. In the BID group, the dose was 45 Gy at 1.5 Gy per twice-daily fraction. Results Data from a total of 143 LD-SCLC patients treated at the Shandong Cancer Hospital & Institute were retrospectively analyzed. Statistically significant differences were found in the rates of both grade 2 or higher esophagitis ( P = 0.036) and pneumonitis ( P = 0.043) between QD and BID groups, respectively. Grade 3 esophagitis occurred in 6% of patients receiving QD and 19% of those receiving BID therapy. The median overall survival ( OS) of all patients was 30.4 months: 29.5 months for QD therapy, and 31.4 months for BID therapy. The two-year OS rate was 43.3% for QD therapy, and 48.8% for BID therapy. The two-year locoregional recurrence-free survival ( LRFS) rate was 45% versus 63.4% for the QD group versus the BID group, respectively. Conclusions Pneumonitis was more common in the QD group, and esophagitis was more common in the BID group. Although there were no significant differences in OS and LRFS between the QD and BID groups, there was a trend toward improved local control in the BID group. [ABSTRACT FROM AUTHOR]

Background and objective Most small cell lung cancer (SCLC) patients relapse or progress and have low survival rate although they have significant response to initial chemotherapy and radiotherapy. This study intends to explore the factors affecting the relapse (or progression) of nonoperative SCLC and to explore the correlations between progression-free survival (PFS) and overall survival (OS). Methods Clinical data of 182 patients diagnosed with SCLC between January 2009 and December 2011 at Shanghai Chest Hospital has been reviewed and retrospectively analyzed. All of these patients accepted chemotherapy combined (or not combined) with radiotherapy, and relapsed or progressed after first-line therapy. Univariate Kaplan-Meier survival estimates as well as multivariate Cox regression survival analysis were used to locate the potential factors affecting PFS. The correlation between PFS and OS was analyzed via Bivariate Correlation Analysis method. Results The univariate estimates showed that the TNM stage, liver metastasis or not, brain metastasis or not, first-line chemotherapy cycles, effect of initial chemotherapy, and thoracic radiotherapy combined or not were the significant contributive factors to PFS. In the subgroup of the patients without brain metastases, those received prophylactic cranial irradiation (PCI) had longer PFS. Cox regression indicated that the three independent variables of first-line chemotherapy cycles, effect of initial chemotherapy and thoracic radiotherapy combined or not were closely related to PFS. In addition, significant positive correlation between PFS and OS had been observed. Conclusion PFS could be prolonged by having more first-line chemotherapy cycles (>4 cycles), obtaining better effect of initial chemotherapy (partial response or complete response), combining with thoracic radiotherapy and implementing PCI for patients without brain metastasis. [ABSTRACT FROM AUTHOR]

Objective To evaluate prognostic risk factors and the effects of platinum-based neoadjuvant chemotherapy (NACT) among patients with small cell carcinoma of the cervix (SCCC). Methods In a retrospective multicenter study, data were analyzed from patients with SCCC diagnosed between July 2001 and October 2009 at one of three hospitals in China. Prognostic risk factors were identified by the Cox proportional hazards model. Results Follow-up information was available for 22 patients, including 18 cases of early (FIGO stage IA–IIA) and four cases of advanced (stage IIB–IV) SCCC. The 3-year disease-free survival (DFS) rate was 62% for patients with early stage disease and 0% for those at a late stage ( P = 0.003). The 3-year overall survival (OS) rate was 68% and 0%, respectively ( P = 0.001). The 3-year OS rate was 73% for patients with no lymphovascular space invasion and 0% for those with lymphovascular space invasion ( P = 0.031). Advanced FIGO stage was the only independent risk factor for 3-year DFS ( P = 0.017) and 3-year OS ( P = 0.006). Patients who received NACT plus radical surgery had a lower rate of distant recurrence than did patients who received radical surgery as the primary treatment (0/8 vs 5/9; P = 0.029). Conclusion Advanced disease was an independent risk factor for SCCC prognosis. Platinum-based NACT seemed to prevent distant recurrence. [ABSTRACT FROM AUTHOR]

Background The treatment status of small cell lung cancer ( SCLC) in Mainland China has never been reported; therefore, this study is the first multicenter survey investigating the status of epidemiology and treatment options of SCLC in Mainland China. Methods Two questionnaires were designed to obtain information in 12 medical centers in five major Chinese cities. The hospital information questionnaire was designed to outline SCLC patients' characteristics and treatment preferences in each medical institution, and the patient information questionnaire collected detailed treatment information of 298 SCLC cases in these hospitals. Results SCLC represented 13.7% and 18.3% of all lung cancer patients in 2005 and 2010, respectively. Clinical management of SCLC follows mainstream clinical guidelines in general. The most widely applied first-line treatment mode for limited-stage patients was combined chemoradiotherapy (66.2%), while 77.0% of the extensive-stage patients received chemotherapy alone as initial treatment. Etoposide with cisplatin or carboplatin were the most accepted first-line chemotherapy regimens. The objective response rate was 58.3% after first-line chemotherapy and 23% of the patients who responded well to first-line treatment received prophylactic cranial irradiation. As for second-line chemotherapy, single regimen topotecan or a combined regimen containing topotecan were preferred (53.0%). Conclusions The treatment options indicated in our study are in accordance with the international clinical guidelines, which is valuable for the improvement of future guidelines, health care standard, and even the better distribution of health care resources in China. [ABSTRACT FROM AUTHOR]

Background: We investigated the relationship between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) based on micro ribonucleic acid (miRNA) and messenger (m)RNA expression profiles. Methods: Utilizing the differentially expressed mRNAs and the targeting miRNAs, the mRNA-miRNA network for the two cancers was constructed. By integrating the miRNA expression profile, drug, and drug targets, miRNA-drug target-drug networks were established and the mechanisms in drug therapy efficacy were compared between SCLC and NSCLC. Results: Drug targets of different expressed miRNAs of SCLC are mainly located in the organelle, act in the electron carrier activity, and consist of the synapse; while drug targets of NSCLCare the membrane-enclosed lumen, mainly distributed in the extracellular region and synapse, and function in the binding. Drug targets of miRNA expressed commonly in the two cancers are involved in the reproduction multi-organism process. In SCLC, the miR-16 in the miRNA-drug target-drug network is significant and follows the result of themRNA-miRNAnetwork.The pigmentation and rhythmic process of SCLCis different fromNSCLC, while the process of cellular component biogenesis and cellular component organization are important for the occurrence of NSCLC. miR-16 in the miRNA-mRNA-drug network of SCLC is significant and we acquired 11 potential drugs, such as dexamethasone and budesonide. The miR-124 for NSCLC is important in the network and 17 potential drugs were screened, including dexamethasone and budesonide. Conclusions: These findings suggest that miR-16 and miR-124 might be novel diagnostic and prognostics markers for SCLC and NSCLC, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Chemoresistance is often developed in small cell lung cancer (SCLC) patients and leads to poor prognosis. Hox genes, a highly conserved family, play a crucial role in apoptosis, receptor signalling and differentiation. MicroRNAs (miRNAs) have also been shown to play a crucial role in these biological processes by regulating the target genes. Several studies reported that both Hox genes and miRNAs are involved in chemoresistance. The aim of our study is to characterise the clinical significance and functional roles of HOXA1 in SCLC. Expression of HOXA1 was examined in 63 cases of SCLC tissues and 29 cases of blood by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) methods. Multivariate analysis confirmed the prognostic significance of HOXA1 in SCLC patients. Restoration of HOXA1 expression was carried out in SCLC multidrug resistant cell line H69AR and its parental cell line H69 to assess its influence on chemoresistance. Luciferase reporter assay was used to assess HOXA1 as a target of miR-100. The results showed that HOXA1 was expressed in 46% (29/63) of SCLC. Low HOXA1 expression was associated with the poor prognosis of SCLC (P <0.05 by the Fisher’s Exact Test) and the shorter survival rate (P <0.001 by the Kaplan–Meier method). HOXA1 expression on both mRNA and protein levels significantly correlated with chemotherapy response. Enforced expression of HOXA1 in resistant H69AR cells led to increased chemosensitivity through increasing cell apoptosis and cell-cycle arrest. Inhibition of HOXA1 expression using HOXA1 siRNA in H69 cells resulted in cell resistance to therapeutic drugs through reducing drug-induced cell apoptosis accompanied with cell cycle arrest. Expression of endogenous miR-100 was significantly elevated in resistant H69AR cells and negatively related with HOXA1 expression. The expression of HOXA1 in SCLC tissues correlated inversely with the expression levels of miR-100. Reporter assays confirmed that miR-100 targeted predicted sites in 3′-untranslated region (3′-UTR) of HOXA1 gene. Our data suggested that HOXA1-mediated SCLC chemoresistance is under the regulation of miR-100. HOXA1 may be a prognostic predictor and potential therapeutic target in human SCLC. [Copyright &y& Elsevier]

Background Overexpression of KIT ( CD117), a tyrosine kinase receptor, and its natural ligand, stem cell factor, are found in small-cell lung cancer ( SCLC). Somatic mutations of the proto-oncogene c-kit constitutively activate KIT expression in a ligand-independent way. To explore the clinical value of the c-kit mutation as a potential target for therapy with tyrosine kinase inhibitors, the c-kit mutational status and KIT expression in tumors from Chinese patients with SCLC were analyzed. Methods Using 107 paraffin-embedded SCLC tumor specimens, c-kit exons 9, 11, 13, and 17 were analyzed for mutations by polymerase chain reaction and direct sequencing. Results There were no activating mutations in exons 9, 11, 13, or 17. However, a point mutation in intron 16 (81240 G>A) was found in 11 out of the 107 samples (10.3%), of which the majority were limited-stage SCLC (10/11, 90.9%). Immunohistochemical staining of tumors harboring the c-kit point mutation using the anti- CD117 antibody showed that the mutation status was not associated with the expression of KIT. Conclusion These findings indicate that the incidence and the types of c-kit mutations in SCLC tumors found in Chinese are different from those of the Caucasian population. Nevertheless, c-kit mutations are similarly rare in both groups, implying that they may not be suitable targets for c-kit-based tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]

Background and objective Different histologies of lung cancer vary in occurrence and prognosis. This study aims to analyze the incidence and occurrence trend of lung cancer and investigate the survival rate and its influential factors among lung cancer patients with different histologies. Methods Permanent residents were recruited between 2002 and 2009 in Pudong New Area (former Nanhui Area and former Pudong Area), Shanghai, China. Annual percent changes were estimated by a linear regression of the logarithm on the incidence rates for eight years. Survival rates were calculated and compared by using life-table analysis and Log-rank test, respectively. Results The standardized incidence rates of lung cancer were 52.28 and 18.86 per 100,000 in males and females, respectively. The median survival time was 410.72 days for specific classified lung cancer. The incidence rates of adenocarcinoma ranked the highest and showed an upward tendency (P<0.05). Patients with small cell lung cancer showed the worst survival condition. The survival condition in males with squamous cell lung cancer living in former Nanhui Area was better compared with those living in former Pudong Area. Conclusion Lung cancers with different histologies demonstrated different occurrence trends and survival rates. Gender, age, and living area influence the survival rates of lung cancer with different histologies. [ABSTRACT FROM AUTHOR]

Background and objective: Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor but highly sensitive to chemotherapy and radiotherapy. At present, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. In this study, we analyzed the survival among all extensive-stage SCLC and patients who received first-line chemotherapy and determined prognostic factors. Methods: Total of 394 patients who were diagnosed as extensive-stage small cell lung cancer from February 2001 to December 2011 hospitalized in Peking Union Medical College Hospital were collected. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the influence factors of survival. Results: The median OS of all extensive-stage small cell lung cancer was 14.8 months; 1-year, 2-year and 5-year survival rates were 58.9%, 27.2% and 7.8%, respectively. According to the results of univariate and Cox multivariate analysis, OS of extensive-stage SCLC was closely associated with age (P=0.006), ECOG PS (P=0.021), liver metastasis (P<0.001), bone metastasis (P<0.001) and chemotherapy (P<0.001). The mortality risk of patients who didn't receive chemotherapy was 4.919 times higher than that who received; the mortality risk of patients without liver, bone metastasis was reduced by approximately 50 percent. The first-line chemotherapy was mainly EP (DDP+VP-16) or CE (CBP+VP-16) regimens (accounting for 82.8%) with 4-6 cycles. The median OS and PFS in first-line chemotherapy were 15.1 months and 7.5 months, respectively. The result of Cox regression analysis indicated that OS in first-line chemotherapy was remarkably related to smoking history (P=0.041), liver metastasis (P<0.001), bone metastasis (P<0.001), chemotherapy cycle number (P<0.001); PFS was relevant with smoking history (P=0.003), liver metastasis (P=0.001), bone metastasis (P<0.001), chemotherapy cycle number (P<0.001). Thoracic radiotherapy was not an independent influence factor of OS and PFS in extensive-stage small cell lung cancer. Conclusion: The patients who were younger than 60-year old, with good KPS, absence of liver and bone metastasis had better prognosis. Patients should receive chemotherapy with first-line standard regimen (CE/EP regimen). It was beneficial to survival if the effect of first-line chemotherapy was SD or PR-CR and the proper chemotherapy cycle number was 4-6 cycles. The role of thoracic radiotherapy in extensive-stage small cell lung cancer needed to be investigated further. [ABSTRACT FROM AUTHOR]

We evaluated the role of surgery followed by either chemotherapy ( ChT) alone or chemotherapy and thoracic radiotherapy ( ChT/TRT) versus sequential ChT/TRT in patients with clinical stage I or stage II small cell lung cancer ( SCLC). Ninety-six patients received surgery (complete resection) followed by either ChT alone or ChT/TRT ( Group I), while 49 patients were treated exclusively with sequential ChT/TRT ( Group II). The ChT regimens consisted of either carboplatin/etoposide or cisplatin/etoposide. The total TRT dose was 50-60 Gy. For the whole group ( n = 145), the median survival time was 54 months, and the 5-year overall survival ( OS) rate was 48%. The corresponding figures for Group I were 91 months and 57%, respectively, and for Group II, they were 34.6 months and 31.4% respectively ( P = 0.004). Multivariate analysis revealed that a Karnofsky Performance Status score ≥ 80 [hazard ratio ( HR), 0.281; P = 0.015] and the treatment modality including surgery ( HR, 0.503; P = 0.004) were independent favourable prognostic factors for OS. [ABSTRACT FROM AUTHOR]

Background Patients with small cell lung cancer ( SCLC) are mainly treated by chemotherapy/radiotherapy, either alone or combined. Surgical resection is an optional treatment for few SCLC patients. The efficacy of surgical intervention for SCLC remains controversial. This study evaluates the validity of surgery for patients with limited stage SCLC. Methods We conducted a retrospective review of 59 patients with limited stage SCLC who received trimodal therapy from 2004 to 2011. Progression-free survival ( PFS) and overall survival ( OS) were calculated using the statistic methods of Kaplan- Meier and the log-rank test. Results Among the 59 limited stage SCLC patients, 54 patients with stage I-III SCLC received surgical treatment with curative intent, and 42.6% (23/54) patients received preoperative chemotherapy. The radical resection rate of the group of preoperative chemotherapy and the group of initial surgical resection were 82.6% (19/23) and 54.8% (17/31), respectively. The corresponding five-year survival rates were 59% and 22% with significant differences (P = 0.032 and 0.041, respectively). In total, 36 (66.7%) patients underwent radical surgery with resection of the primary mass and mediastinal lymph nodes. In the radical surgery series, five-year survival, according to stage I-III categories, were 59%, 53%, and 26%, respectively. For the 30 stage III patients, the five-year survival of the radical group of 26% was lower than the non-radical group of 67%, and PFS analysis showed similar tendencies. Conclusion Preoperative chemotherapy is the most favorable initial treatment for patients with limited disease SCLC. Complete surgical resection is considered for patients with stage I and II. Surgical resection remains of no benefit for stage III SCLC patients with persistent N2/ N3 after chemotherapy. [ABSTRACT FROM AUTHOR]

Background Maintenance therapy for extensive stage small cell lung cancer ( ES-SCLC) is still under debate. Many new agents fail during the maintenance course. As an active agent for SCLC, oral etoposide is worth being re-evaluated. Methods This phase II study was performed to evaluate the toxicity/efficacy of the maintenance of patients with oral etoposide with ES-SCLC responding (complete remission [ CR] + partial remission [ PR]) to the induction of four cycles of etoposide plus cisplatin ( EP) chemotherapy. Maintenance therapy with oral etoposide (50 mg/m2, day 1-14, repeated every 21 days until disease progression or unacceptable toxicity occurs) was administered. The primary endpoints were grade 3 and 4 toxicities and progression free survival ( PFS). Results Fifty-four patients with ES-SCLC received standard EP regimens as induction therapy; 31 responding patients were administered oral etoposide as the maintenance treatment. The most common hematological and non-hematological toxicity of the maintenance course was neutropenia and fatigue, respectively. Median PFS was nine months (95% confidence interval ( CI): 8.33∼9.67 months), median overall survival ( OS) was 14 months (95% CI: 11.58∼16.42 months). Significantly better PFS and OS were seen in patients responding to the induction EP chemotherapy. Conclusions Oral etoposide maintenance is safe and effective for patients with ES-SCLC who responded to the induction of EP chemotherapy. Significant survival benefit was revealed in patients completely responding to an EP regimen. Further randomized control study is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Small cell carcinoma of esophagus (SCEC) is characterized by high malignancy and early metastasis. Although the morbidity of SCEC is very low, few studies of patients with SCEC have been conducted in China, there are no sufficient studies of SCEC conducted and reported in the existing published works, and the choices of treatment remain controversial. In this work, we aim to study the clinical characteristics of SCEC, and explore the corresponding treatment and prognosis through retrospective analysis. Material and Methods: The original articles were identified through the leading digital libraries in China in which the terms 'esophagus or esophageal' and 'small cell esophageal carcinoma' appeared from 2005 to 2009, 1,176 eligible cases were reviewed for clinical data. Analysis of survival was conducted using the Kaplan-Meier method, and differences were compared using the log-rank test. Results: One thousand one hundred seventy-six eligible cases were analyzed; the median age of patients was 57 years, with a male-to-female ratio of 2.4:1. The number of SCEC accounted for 1.26 % of esophageal cancer treated in the same period. Of the tumors, 89.7 % were located in mid- and lower thoracic esophagus. The average tumor length was 5.4 cm (0.5-17 cm). The median overall survival was 11.1 months for all patients. The 1-, 2-, 3-, and 5-year average overall survival rates of 469 patients was 51.1, 25.5, 13.2, 7.9 %, respectively. The median survival time for LD patients who received systemic treatment was 16.8 m, whereas for those who received local treatment (surgery), the median survival time was 10.1 m; the median survival time for ED patients who received systemic treatment was 7.4 m, compared with 5.8 m for those who received sole treatment (chemotherapy or radiotherapy). Conclusions: SCEC is a tumor characterized by high malignancy and early metastasis. Although our retrospective analysis cannot provide definitive conclusions on the optimal treatment modality for SCEC, however, our results suggest that systemic treatment combined with surgical resection plays a major role in the therapy of SCEC, systemic therapy may be an effective approach for the treatment of SCEC, and randomized, prospective, multicenter studies are needed to identify optimal treatment modalities for SCEC [ABSTRACT FROM AUTHOR]

Background: The management of limited-disease esophageal small cell carcinoma is not well defined, and the role of surgery is still controversial. We aim to determine the optimal treatment strategy in limited-disease of esophageal small cell carcinoma. Methods and Findings: We conducted a retrospective review of 141 patients with limited-disease esophageal small cell carcinoma from 3 institutions in China who underwent treatment between July 1994 and September 2008, July 1994 and July 2011, and June 2004 and December 2010, respectively. The survival rate was calculated by the Kaplan-Meier method, and the log-rank test was used to assess the survival differences between the groups. Cox proportional hazards model were used to further determine the independent factors impacting overall survival. The median survival time was 16.1 months for the entire cohort of patients, with a 5-year survival rate of 6.7%. The median survival times for surgery alone, surgery combined with chemotherapy, surgery combined with radiotherapy, surgery combined with chemotherapy and radiotherapy, chemotherapy plus radiotherapy, and chemotherapy alone were 18.0 months, 15.0 months, 23.0 months, 25.0 months, 17.1 months, and 6.1 months, respectively; the corresponding 5-year survival rates were 0%, 15.4%, 0%, 38.9%, 0%, and 0%, respectively. For the 105 patients who underwent R0 resection, the median disease-free survival time was 12.0 months, with a 95% confidence interval of 9.5 months to 14.5 months. The multivariate Cox regression analysis demonstrated that advanced pathological staging (p = 0.003), and pure esophageal small cell carcinoma (p = 0.035) were independent factors decreasing overall survival. Conclusions: Our data suggested that multidisciplinary modalities achieved encouraging long-term survival in patients with resectable limited-disease of esophageal small cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: This study presents the characteristics and treatment of small cell lung cancer (SCLC) and an analysis of the factors that impact survival in northeastern Chinese populations, among both smokers and non-smokers. Methods: A retrospective review was performed using 485 Chinese patients diagnosed with pathologically confirmed SCLC diagnoses between January 2001 and December 2007. Data on patient characteristics, treatment patterns, and outcome information was collected systematically. Univariate analysis and the Cox multivariate regression model were used to evaluate prognostic factors. Results: Median survival time was 16 months in all patients, 31 months in limited stage (LS) patients, and 10 months in extensive-stage (ES) patients. Never-smoking patients ( P= 0.0368) with good performance status (PS) ( P= 0.0044) or with normal lactate dehydrogenase (LDH) levels ( P < 0.0001), demonstrated superior survival rates. Multivariate analysis identified that cycles of chemotherapy, PS, LDH levels, recurrence or progression, and clinical stage were each independent prognostic factors applicable to all patients. In LS-SCLC, cycles of chemotherapy were the only prognostic indicator; however, cycles of chemotherapy, LDH levels, and recurrence or progression, were all significant factors in ES-SCLC. Conclusion: Cycles of chemotherapy, PS, LDH levels, recurrence or progression, and clinical stage were proved to be independent prognostic factors for SCLC with variant value based on the SCLC tumor stage. [ABSTRACT FROM AUTHOR]