Small Cell Carcinoma Of The Esophagus Research Articles

Multimodality Therapy and Survival Outcomes in Resectable Primary Small Cell Carcinoma of the Esophagus: A Multicenter Retrospective Study.

Currently, optimal treatment strategy for resectable primary small cell carcinoma of the esophagus (PSmCCE) remains controversial. To address this, we conducted a multicenter study to evaluate treatment patterns and long-term survival of PSmCCE patients who underwent radical resection. This retrospective multicenter study included resected PSmCCE patients who received radical resection at seven high-volume cancer centers. Overall survival (OS) and median survival time (MST) were calculated by using a Kaplan-Meier method and the log-rank test was utilized to assess differences. Multivariable Cox analysis was performed to identify independent prognostic factors. A total of 352 patients with resected PSmCCE were included. For PSmCCE with stage cT1-2N0M0, patients who received surgery plus adjuvant therapy showed better survival than those who received surgery alone (5-year OS rate: 32.8% vs. 19.2%, MST: 44.0 vs. 33.0 months, P = 0.035). Multivariable Cox survival analysis revealed an independent correlation between receiving surgery plus adjuvant therapy and improved OS (hazard ratio [HR] 0.529; 95% confidence interval [CI] 0.280-0.997; P = 0.049). For stage cT3N0M0/T1-3N1M0 PSmCCE, patients who received neoadjuvant therapy followed by surgery had superior long-term survival compared with those who received surgery combined with adjuvant therapy and those who received surgery alone (5-year OS rate: 27.2% vs. 9.5% vs. 0%, MST: 36.0 vs. 24.0 vs. 20.0 months, P = 0.014). Multivariable Cox survival analysis showed that neoadjuvant therapy was independently associated with improved OS (HR 0.384, 95% CI 0.203-0.728; HR 0.550, 95% CI 0.312-0.968; P = 0.013). Adjuvant therapy was associated with improved survival in stage cT1-2N0M0 PSmCCE, but this should be confirmed in prospective studies. For stage cT3N0M0/T1-3N1M0 cases, neoadjuvant therapy followed by surgery should be considered.

Small cell cancer of the esophagus, treatment outcomes of a rare histological type

Purpose: To demonstrate treatment outcomes in two patients with small cell esophageal cancer. Cases reports. Patient M. was assigned to receive polychemotherapy (PC H) composed of etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days, followed by chemoradiotherapy (CRT). The patient received 1 cycle of PCT , which was well tolerated. Then, the patient received a cycle of 3D-conformal radiation therapy concurrently with 2 cycles of chemotherapy: etoposide 120 mg/m2 + cisplatin 80 mg/m2. Chemoradiotherapy was well tolerated. Dysphagia regression to grade I was observed. Currently, the patient continues to receive treatment (etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days) and tolerates it well. Patient A. was assigned to receive PCT with etoposide 120 mg/m2 + cisplatin 80 mg/m2. After 4 cycles of PCT , the follow-up CT images revealed disease progression (enlarged retroperitoneal lymph nodes). The patient underwent external bean radiation therapy to the primary tumor. Radiotherapy was relatively well tolerated. The patient underwent the course of radiation therapy relatively satisfactorily. Due to the progression of the disease, symptomatic treatment was assigned. The patient died 9 months after diagnosis. Conclusion. Small cell carcinoma of the esophagus is a rare histological type with poor prognosis. Concurrent platinum-based chemoradiotherapy allows achievement of stable disease and disease control.

Patterns and prognostic values of programmed cell death-ligand 1 expression and CD8 + T-cell infiltration in small cell carcinoma of the esophagus: a retrospective analysis of 34 years of National Cancer Center data in China.

Small cell carcinoma of the esophagus (SCCE) is an extremely rare and highly aggressive neuroendocrine malignancy with a strikingly poor prognosis. Given the great clinical successes of checkpoint immunotherapies, we explored the expression profile and clinical significance of programmed cell death-ligand 1 (PD-L1) and CD8 + T cell in SCCE for the first time. Tumor-infiltrating immune cells (TIICs) and tumor cells in postoperative, whole tumor sections from 147 SCCE patients were stained for PD-LI expression. We also evaluated each patient's Combined Positive Score (CPS). Multiplex immunofluorescence staining (CD3, CD20, CD68, and PD-L1) was introduced to clarify the location of PD-L1. CD8 density was analyzed by digital imaging and analysis of entire slides. Clinical outcomes were tested for correlations with both PD-L1 expression and CD8 density. No patients had PD-L1 expressed in their tumor cells. PD-L1 + expression in TIICs was detected in 65 patients (44.2%) and 42 (28.6%) exhibited CPS positivity. Multiplex immunofluorescence staining demonstrated that most of the PD-L1 was expressed on the CD68 + monocytes/macrophages. PD-L1 expression in the TIICs and CPS was found to be correlated with paraffin block age, tumor length, macroscopic type, T stage, and increased overall survival (OS). Expression of PD-L1 in TIICs showed significantly prolonged relapse-free survival (RFS). Increasing CD8 densities were associated with increased PD-L1 expression ( Ptrend <0.0001). Multivariate regression confirmed that PD-L1 in TIICs and CD8 states were independent predictors of OS, and CD8 status were found to be independently predictive of RFS. A stratification based on PD-L1 and CD8 status was also significantly associated with both OS and RFS. Expression of PD-L1 was only detected in TIICs from approximately half of the patients with SCCEs. In SCCEs, PD-L1 and CD8 status are novel prognostic biomarkers and may inform the implementation of risk-related therapeutic strategies. SCCEs with higher CD8 infiltration also had higher expression of PD-L1, suggesting the development of resistance against adaptive immunity. These findings support the assertion that PD-L1/programmed cell death 1 inhibitors should be investigated in this rare malignancy.

The Applicability of the AJCC TNM Staging 8th Edition to Esophageal Small-Cell Carcinoma: A Multicenter Retrospective Trial from China

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.

Primary Small Cell Carcinoma of the Esophagus in a Large Multicenter Cohort: Prognostic Factors and Treatment Strategies in the Modern Era

Primary small cell carcinoma of esophageal (PSCCE) is a rare malignancy with aggressive behavior associated with a perceived poor prognosis. Due to its rarity, the clinical characteristics and the optimal clinical management have not yet been defined, therefore, we designed a multicenter retrospective study to analyze the prognostic factors and the impact of treatment on the prognosis of PSCCE patients. We retrospectively evaluated 704 consecutive patients with PSCCE from five participating centers between April 2008 and July 2021. The PSCCE was diagnosed based on the World Health Organization classification. Treatment strategies included surgery, radiotherapy (RT), or chemotherapy only, and combination of 2-3 treatment modalities (surgery, RT and chemotherapy). The estimated hazard rates provide the trajectory of progression and death overtime. Univariate survival analysis was conducted by using Kaplan-Meier plots, and the log-rank test was used to compare survival differences. Cox regression analysis was used to determine the independent prognostic factors in multivariate analysis. Overall, 69.0% (486/704) of the patients were male, with a median age of 63 years (range 38-96). Most of the patients were regional lymph node positive (N+, 64.0%), and nearly half with advanced stage (M+, 47.2%). With a median follow-up time of 16 months, 472 patients (67.0%) exhibited disease progression and 429 patients (60.9%) died. Following initial treatment, 85.1% (402/472) of progression/death and 80.1% (344/429) of mortalities occurred within 24 months. Consistently, the maximum annual death and progression/death hazards are highest in the 15.6 months and 9.6 months. The overall survival (OS) rates at 1, 3 and 5 years for all patients were 65.1%, 26.5% and 18.3%, respectively. Univariate survival analysis showed that ECOG score, alcohol abuse, TNM stage, N stage, and M stage were correlated with OS (P <0.05). Multivariate analysis showed that the N stage (HR: 1.378, P = 0.018) and M stage (HR: 1.945, P <0.001) carried independent prognostic factors for OS. In the term of treatment, the OS rates for M- patients treated with combined modality therapy (CMT, surgery±radiotherapy/chemotherapy) were better than those treated with surgery alone or radiotherapy/chemotherapy (3-year OS: 36.7% VS 25.6% VS 32.2%; P = 0.045). The OS rates for M+ patients treated with chemotherapy alone, radiotherapy alone, or radiotherapy combined with chemotherapy were no significant differences (3-year OS: 12.2% VS 19.4% VS 11.1%; P = 0.400). PSCCE is characterized by a high degree of malignancy with high risks of lymphatic and distant metastasis, N and M stages are the most important prognostic factor. In terms of treatment, comprehensive treatment is most likely to benefit patients without distant metastasis.

Radical Chemoradiotherapy vs. Radical Surgery plus Adjuvant Chemotherapy or Chemoradiotherapy in Locally Advanced Primary Small Cell Carcinoma of the Esophagus: A Multicenter Retrospective Study in China

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.

Pattern of Lymph Node Metastases and its Implication in Radiotherapeutic Clinical Target Volume in Patients with Small Cell Carcinoma of the Esophagus

<h3>Purpose/Objective(s)</h3> 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. <h3>Materials/Methods</h3> 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. <h3>Results</h3> 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 (<i>P</i><0.05). <h3>Conclusion</h3> 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.

Treatment Strategies for Limited-Stage Primary Small Cell Carcinoma of the Esophagus: A Multicenter Retrospective Trial from China

<h3>Purpose/Objective(s)</h3> 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. <h3>Materials/Methods</h3> 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). <h3>Results</h3> 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 (<i>P</i> < 0.001). Moreover, progression-free survival (PFS), locoregional PFS, and distant PFS were also significantly different between the two groups (<i>P</i> < 0.05). <h3>Conclusion</h3> 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.

Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus.

BACKGROUNDPrimary small cell carcinoma of the esophagus (PSCE) is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma. Due to the limited samples size and the short follow-up time, there are few reports on elucidating the prognosis of PSCE, especially on the establishment and validation of a survival prediction nomogram model covering general information, pathological factors and specific biological proteins of PSCE patients.AIMTo establish an effective nomogram to predict the overall survival (OS) probability for PSCE patients in China.METHODSThe nomogram was based on a retrospective study of 256 PSCE patients. Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE, and establish the model for predicting 1-, 3-, and 5-year OS based on the Akaike information criterion. Discrimination and validation were assessed by the concordance index (C-index) and calibration curve and decision curve analysis (DCA). Histology type, age, tumor invasion depth, lymph node invasion, detectable metastasis, chromogranin A, and neuronal cell adhesion molecule 56 were integrated into the model.RESULTSThe C-index was prognostically superior to the 7th tumor node metastasis (TNM) staging in the primary cohort [0.659 (95%CI: 0.607-0.712) vs 0.591 (95%CI: 0.517-0.666), P = 0.033] and in the validation cohort [0.700 (95%CI: 0.622-0.778) vs 0.605 (95%CI: 0.490-0.721), P = 0.041]. Good calibration curves were observed for the prediction probabilities of 1-, 3-, and 5-year OS in both cohorts. DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging .CONCLUSIONOur nomogram can be used to predict the survival probability of PSCE patients, which can help clinicians to make individualized survival predictions.

The prognostic value of TCF1+CD8+T in primary small cell carcinoma of the esophagus.

TCF1+CD8+T cells are reported to exhibit stem‐like properties with the ability to self‐renew and differentiate into terminal effector T cells (TCF1‐CD8+T cells) to enhance antitumor response. Previous studies indicated that TCF1+CD8+ tumor‐infiltrating lymphocytes (TILs) are related to response to immunotherapy. However, their role in predicting prognosis for patients with primary small cell carcinoma of the esophagus (PSCCE) remains unclear. In this study, the expression of TCF1+CD8+T was analyzed by multiplex fluorescence immunohistochemistry in tumor tissues of 79 patients with PSCCE. High infiltration of TCF1+CD8+T cells had longer overall survival (OS) than low infiltration (P = .009, hazard ratio [HR] = 0.506). High TCF1+CD8/CD8 ratio (>21%) showed superior OS compared with low ratio (≤21%) (P < .001, HR = 0.394). In the validation set (n = 20), the prognostic value of TCF1+CD8+T cells on OS was also verified. TCF1+CD8+T cells are strong prognostic predictors.

Preoperative Chemotherapy for Limited-stage Small Cell Carcinoma of the Esophagus

BackgroundThe optimal treatment approach for limited-stage small cell carcinoma of the esophagus remains uncertain. This study aimed to evaluate the efficacy and safety of preoperative chemotherapy in combination with surgery vs upfront surgery in those patients. MethodsFrom June 2001 to June 2015, a total of 280 patients with limited-stage small cell carcinoma of the esophagus were screened from 60 131 patients with esophageal cancer. Outcome analysis of those patients who underwent preoperative chemotherapy in combination with surgery or upfront surgery was conducted. The primary end point was overall survival, and secondary end points included progression-free survival and safety. ResultsOf the 280 patients, 200 were men (71.4%), the median age was 64 years (range, 42-75 years), 171 patients (61.1%) patients had preoperative chemotherapy in combination with surgery, and 109 patients (38.9%) underwent upfront surgery. A pathologic complete response rate of 8.8% was noted in patients who received preoperative chemotherapy. Compared with the upfront surgery group, the preoperative chemotherapy group had a better median overall survival (26.0 months vs 19.5 months, respectively; hazard ratio, 0.69; 95% CI, 0.51 to 0.92; P = .011) and a prolonged progression-free survival (16.0 months vs 13.0 months, respectively; hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P = .039). Postoperative complications and peritreatment mortality were comparable between both groups. ConclusionsCompared with upfront surgery, preoperative chemotherapy in combination with surgery improves overall survival in patients with limited-stage small cell carcinoma of the esophagus.

A Rare Case of Primary Small Cell Carcinoma of Esophagus

Primary small cell carcinoma of the esophagus is a rare, highly aggressive disease with a poor prognosis. A definitive diagnosis is made by histopathological study. As the disease is usually metastatic, palliative chemoradiotherapy is the usual treatment. We present a case of a 57-year-old female presenting with dysphagia. The patient underwent imaging studies showing the growth at the gastro-esophageal junction, with extensive abdominal lymph node metastasis and liver and lung metastasis. Biopsy was suggestive of small cell carcinoma of the esophagus. The patient underwent a feeding jejunostomy and was planned for chemoradiotherapy. Primary small cell carcinoma of the esophagus is an infrequent entity. As the disease is usually diagnosed at a later stage, the prognosis is inferior and abysmal.

P-151 The prognostic value of TCF1+CD8+T cell in primary small cell carcinoma of the esophagus

TCF1+CD8+T cells are reported to exhibit stem-like properties with the ability to self-renew and differentiate into terminal effector T cells (TCF1-CD8+T cells) to enhance anti-tumor response. Previous studies indicated that TCF1+CD8+TILs are related to response to immunotherapy. However, their role in predicting prognosis remains unclear. Here, we investigated the prognostic value of TCF1+CD8+T cells in patients with primary small cell carcinoma of the esophagus (PSCCE). The tumor tissues from 79 patients with PSCCE were analyzed by multiple immunofluorescence staining. The optimal cut-off value and corresponding sensitivities and specificities were determined by time-dependent receiver-operating characteristic (ROC) curves. The percentage of indicators in all tumor cells were used to define expression levels. The Kaplan–Meier method and Cox proportional hazards model were used to analyze survival distributions. High TCF1+CD8+T cells infiltration has longer OS than low infiltration (31 vs 17 months, p=0.009, HR=0.506). TCF1+CD8/ CD8 ratio＞21% showed superior OS than ≤21% (31 vs 16 months, p＜0.001, HR=0.394). In patients with high CD8+T infiltration, high ratio shows better OS (32 vs 19 months, P=0.042, HR=0.511). We identified intratumoral stem-like T cells (TCF1+CD8+T) abundance in PSCCE. High infiltration of TCF1+CD8+T cell is related to better clinical outcomes. TCF1+CD8/CD8 ratio is a strong and independent prognostic predictor.

Multi-omics profiling of primary small cell carcinoma of the esophagus reveals RB1 disruption and additional molecular subtypes

Primary small cell carcinoma of the esophagus (PSCCE) is a lethal neuroendocrine carcinoma. Previous studies proposed a genetic similarity between PSCCE and esophageal squamous cell carcinoma (ESCC) but provided little evidence for differences in clinical course and neuroendocrine differentiation. We perform whole-exome sequencing, RNA sequencing and immunohistochemistry profiling on 46 PSCCE cases. Integrated analyses enable the discovery of multiple mechanisms of RB1 disruption in 98% (45/46) of cases. The transcriptomic landscape of PSCCE closely resembles small cell lung cancer (SCLC) but differs from ESCC or esophageal adenocarcinoma (EAC). Distinct gene expression patterns regulated by ASCL1 and NEUROD1 define two molecular subtypes, PSCCE-A and PSCCE-N, which are highly similar to SCLC subtypes. A T cell excluded phenotype is widely observed in PSCCE. In conclusion, PSCCE has genomic alterations, transcriptome features and molecular subtyping highly similar to SCLC but distinct from ESCC or EAC. These observations are relevant to oncogenesis mechanisms and therapeutic vulnerability.

Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung

Small-cell carcinoma of the esophagus (SCCE) is a rare and aggressive cancer. Although several consistent genomic changes were observed previously between SCCE and small-cell lung cancer (SCLC), detailed mutational landscapes revealing discrepancies in genetic underpinnings of tumorigenesis between these two cancers are scarce, and little attention has been paid to answer whether these genetic alterations were related to the prognosis. Herein by performing whole-exome sequencing of 48 SCCE and 64 SCLC tumor samples, respectively we have shown that the number of driver mutations in SCCE was significantly lower than in SCLC (p = 0.0042). In SCCE, 46% of recurrent driver mutations were clonal, which occurred at an early stage during tumorigenesis, while 16 driver mutations were found clonal in SCLC. NOTCH1/3, PIK3CA, and ATM were specifically clonal in SCCE, while TP53 was clonal in SCLC. The total number of clonal mutations differed between two cancers and presented lower in SCCE compared to SCLC (p = 0.0036). Moreover, overall survival (OS) was shorter in patients with higher numbers of clonal mutations for both cancers. In summary, SCCE showed distinct mutational background and clonal architecture compared with SCLC. Organ-specific clonal events revealed different molecular mechanisms underlying tumorigenesis, tumor development, patients’ prognosis, and possible variations in therapeutic outcomes to candidate treatments.

Survival outcomes and prognostic factors of primary small cell carcinoma of the esophagus.

BackgroundPrimary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive malignancy. It has a poor survival rate, and there is no consensus as to a standard therapeutic modality. In this study, we aimed to investigate the prognostic factors and evaluate the outcomes of patients with PSCCE who had been treated with different therapeutic methods.MethodsWe retrospectively evaluated 113 consecutive patients with PSCCE who received treatment at our center from 2003 to 2016. The primary endpoint was overall survival (OS). The Cox regression model was used to analyze the prognostic factors. The survival analysis was calculated using the Kaplan-Meier and log-rank methods.ResultsThe 12- and 36-month OS rates of all 113 enrolled patients were 45% and 12%, respectively. A significantly prolonged OS rate was associated with lymph node stages N0–N1 (P=0.022), the Veterans’ Administration Lung Study Group (VALSG) system limited-disease (LD) staging (P=0.040), and multimodality treatments (P=0.047). Patients with regional lymph node metastasis benefited more from surgery combined with chemotherapy than surgery or chemotherapy alone (P=0.046). Concerning chemotherapy, cisplatin plus etoposide was the regimen most commonly used to treat PSCCE patients (67.5%).ConclusionsAn early lymph node stage, the VALSG LD staging, and multimodality treatments were identified as independent prognostic factors of PSCCE. Surgery combined with adjuvant chemotherapy was especially necessary for LD stage PSCCE patients with lymph node stages N1–3.

Nomogram for predicting the survival of patients with small cell carcinoma of the esophagus: A population study based on the surveillance, epidemiology, and end results database.

This study aims to establish an effective prognostic nomogram for small cell carcinoma of the esophagus (SCCE).A total of 552 patients with SCCE from 1975 to 2016 were extracted from the surveillance, epidemiology, and end results (SEER) database. A Cox proportional hazard regression model was used to analyze the prognostic factors of patients, and a nomogram was constructed. The nomogram was then validated internally by using a consistency index (C-index) and a correction curve to evaluate its predictive value.The Cox proportional hazard regression model showed that age, stage, surgery, primary site, radiotherapy, and chemotherapy were the prognostic factors of SCCE (P < .1), and they were used to construct the nomogram. The C-index of the nomogram for predicting survival was 0.749 (95% confidence interval [CI] = 0.722–0.776). The data were randomly divided into a modeling group and a validation group based on 7:3 for internal validation. The C-indices of the modeling and validation groups were 0.753 and 0.725, respectively, and they were close to 0.749. The calibration curves exhibited good consistency between the predicted and actual survival rates.The nomogram of the survival and prognosis of patients with SCCE in this study had a good predictive value and could provide clinicians with accurate and practical predictive tools. It could also be used to facilitate a rapid and accurate assessment of patients’ survival and prognosis on an individual basis.

CD155 Overexpression Correlates With Poor Prognosis in Primary Small Cell Carcinoma of the Esophagus.

CD155/TIGIT overexpression has been detected in various human malignancies; however, its expression status in primary small cell carcinoma of the esophagus (PSCCE) and its prognostic significance remain unclear. In this study, we aimed to explore the expression and prognostic value of CD155 and TIGIT in PSCCE. We detected CD155 and TIGIT expression in 114 cases of PSCCE using immunohistochemistry (IHC) and evaluated their relationship with the clinicopathological characteristics and survival of the patients. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. Nomogram performance was assessed via the concordance index (C-index) and calibration plots. Decision curve analysis (DCA) was performed to evaluate the net benefit of the nomogram. We found that CD155 and TIGIT were overexpressed in PSCCE tissues, CD155 expression correlated positively with TIGIT (p < 0.001) and was significantly associated with tumor size, T stage, distant metastasis, TNM stage, and Ki-67 score. TIGIT expression was also significantly associated with T stage, distant metastasis, and TNM stage. Patients with high CD155 and TIGIT expression had a significantly shorter overall survival (OS) and progression-free survival (PFS), while the multivariate model showed that CD155 expression and the therapeutic strategy are independent prognostic factors for PSCCE. In the validation step, OS was shown to be well-calibrated (C-index = 0.724), and a satisfactory clinical utility was proven by DCA. In conclusion, our findings revealed that CD155 and TIGIT are highly expressed in patients with PSCCE and are associated with shorter OS and PFS, supporting their role as prognostic biomarker.

Chemotherapy Plus Radiotherapy Versus Radiotherapy in Patients With Small Cell Carcinoma of the Esophagus: A SEER Database Analysis.

Background:Small cell carcinoma of the esophagus is a rare malignant tumor. We aimed to explore the chemotherapeutic efficacy on the prognosis of patients with small cell carcinoma of the esophagus who received radiotherapy.Methods:To identify the population of interest, Surveillance, Epidemiology, and End Results data from 1996 to 2016 were chosen. Univariate and multivariate analyses were used to probe into prognosis factors. Multivariate Cox regression analysis was conducted to identify factors related to overall survival and cancer-specific survival.Results:Overall, data from 162 patients were analyzed in this study. Tumor size (P = 0.014), T staging (P = 0.028), and chemotherapy (P < 0.001) were independent prognostic factors affecting overall survival. Patients with regional disease (hazard ratio = 5.435, P < 0.001) and distant metastasis (hazard ratio = 2.183, P < 0.001) who received radiotherapy alone had worse survival than those receiving chemoradiotherapy. Tumor size (P = 0.004) and chemotherapy (P < 0.001) were independent prognostic factors affecting cancer-specific survival. Tumor size was an independent factor affecting cancer-specific survival for patients receiving chemoradiation.Conclusions:Age, T staging, tumor size, primary site, and chemotherapy are independent prognosis factors affecting overall survival and cancer-specific survival in patients with small cell carcinoma of the esophagus who receive radiotherapy. Chemotherapy might further improve cancer-specific survival in patients with small cell carcinoma of the esophagus receiving radiotherapy at all stages.

SMALL CELL CARCINOMA OF ESOPHAGUS: A CASE SERIES OF SIX PATIENTS

Objective: To study the clinicopathological and oncological outcomes of all the patients presenting with a diagnosis of small cell carcinoma of the esophagus at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC). Methodology: From 1997 to 2017 all patients with a diagnosis of small cell carcinoma of the esophagus were included in the study. Demographic variables were collected. Clinico-pathological outcomes of disease were recorded. All data were entered and analyzed in SPSS ver 21. Results: A total of 6 patients were included in the study. The median age was 63.5 +/- 8.09 years. There were 1 male and 5 female patients. The most common presentation was dysphagia in all 6 patients. Upper gastrointestinal endoscopy was used to detect the location and diagnosis of the disease. A computed tomography scan is used for staging the disease. All patients received neoadjuvant chemoradiotherapy, one patient had surgical resection of the tumour. Almost all patients developed metastases or progression of the disease. Conclusion: Small cell carcinoma of the esophagus is rare and needs to be managed aggressively. All patients are best treated with formal systemic and local treatment.