Background and purpose:Limited-stage(LS)-small cell esophageal carcinoma(SCEC),characterized by high aggressiveness and an extremely poor prognosis,lacks standardized staging systems due to its rarity.Consequently,no randomized controlled clinical trials exist to guide therapeutic strategies,necessitating reliance on extrapolated protocols from small cell lung cancer(SCLC)paradigms,though clinical outcomes remain dismal.This study aimed to analyse survival outcomes,prognostic factors,failure patterns and therapeutic strategies in patients with LS-SCEC.Methods:We conducted a retrospective single-center study of LS-SCEC patients diagnosed and treated at Fudan University Shanghai Cancer Center from January 2006 to June 2023.Clinicopathological data for diagnosis,staging and follow-up were rigorously collected.Patients with mixed esophageal tumors in whom small cell carcinoma was not the predominant histological component(＜50%)were excluded.Continuous variables were presented as x±s.Categorical variables were summarized as counts and percentages,with intergroup comparisons performed using χ2 test or Fisher's exact tests.Survival analysis was performed using the Kaplan-Meier method,and Cox regression was used to analyse factors related to prognosis.A two-sided P＜0.050 was considered statistically significant.A 1∶1 nearest-neighbour propensity score matching was applied to compare survival outcomes between patients undergoing radical chemoradiotherapy and those receiving radical surgery followed by adjuvant chemotherapy.Results:Of 261 eligible LS-SCEC patients included,the median follow-up duration was 72.7 months(95%CI:52.0-92.4),with a median cancer-specific survival(CSS)of 24.5 months(95%CI:19.7-29.3)and a 5-year CSS rate of 32.8%.The median progression-free survival(PFS)was 12.0 months(95%CI:10.7-13.3).Among these,67 patients remained recurrence-free,and 169 patients exhibited disease progression after first-line treatment.Distant metastasis was the predominant recurrence pattern(131 patients,77.5%),whereas locoregional recurrence occurred in only 38 patients(22.5%).The most frequent metastatic sites were liver(54 patients),followed by bone(25 patients),brain(24 patients),and lung(23 patients).The number of chemotherapy cycle and TNM stage(8th edition)were independent prognostic factors for CSS and PFS in LS-SCEC patients.Comparative analysis of radical surgery with adjuvant chemotherapy versus radical chemoradiotherapy revealed no statistically significant differences in CSS and PFS(P＞0.05),even after propensity score matching.Patients with cervical/upper thoracic tumors,longer tumor lengths,and advanced stages were more likely to receive chemoradiotherapy;additionally,the chemoradiotherapy group had a higher proportion of patients completing≥4 chemotherapy cycle.Conclusion:This large-sample retrospective study with comprehensive datasets and long-term follow-up demonstrated comparable survival outcomes between radical chemoradiotherapy and radical surgery plus adjuvant chemotherapy for LS-SCEC.A minimum of 4 chemotherapy cycle was associated with improved prognosis.SCEC is associated with a high risk of distant metastasis and marked heterogeneity.Therefore,the treatment of LS-SCEC should prioritize an individualized approach.

Background and purpose:Limited-stage(LS)-small cell esophageal carcinoma(SCEC),characterized by high aggressiveness and an extremely poor prognosis,lacks standardized staging systems due to its rarity.Consequently,no randomized controlled clinical trials exist to guide therapeutic strategies,necessitating reliance on extrapolated protocols from small cell lung cancer(SCLC)paradigms,though clinical outcomes remain dismal.This study aimed to analyse survival outcomes,prognostic factors,failure patterns and therapeutic strategies in patients with LS-SCEC.Methods:We conducted a retrospective single-center study of LS-SCEC patients diagnosed and treated at Fudan University Shanghai Cancer Center from January 2006 to June 2023.Clinicopathological data for diagnosis,staging and follow-up were rigorously collected.Patients with mixed esophageal tumors in whom small cell carcinoma was not the predominant histological component(＜50%)were excluded.Continuous variables were presented as x±s.Categorical variables were summarized as counts and percentages,with intergroup comparisons performed using χ2 test or Fisher's exact tests.Survival analysis was performed using the Kaplan-Meier method,and Cox regression was used to analyse factors related to prognosis.A two-sided P＜0.050 was considered statistically significant.A 1∶1 nearest-neighbour propensity score matching was applied to compare survival outcomes between patients undergoing radical chemoradiotherapy and those receiving radical surgery followed by adjuvant chemotherapy.Results:Of 261 eligible LS-SCEC patients included,the median follow-up duration was 72.7 months(95%CI:52.0-92.4),with a median cancer-specific survival(CSS)of 24.5 months(95%CI:19.7-29.3)and a 5-year CSS rate of 32.8%.The median progression-free survival(PFS)was 12.0 months(95%CI:10.7-13.3).Among these,67 patients remained recurrence-free,and 169 patients exhibited disease progression after first-line treatment.Distant metastasis was the predominant recurrence pattern(131 patients,77.5%),whereas locoregional recurrence occurred in only 38 patients(22.5%).The most frequent metastatic sites were liver(54 patients),followed by bone(25 patients),brain(24 patients),and lung(23 patients).The number of chemotherapy cycle and TNM stage(8th edition)were independent prognostic factors for CSS and PFS in LS-SCEC patients.Comparative analysis of radical surgery with adjuvant chemotherapy versus radical chemoradiotherapy revealed no statistically significant differences in CSS and PFS(P＞0.05),even after propensity score matching.Patients with cervical/upper thoracic tumors,longer tumor lengths,and advanced stages were more likely to receive chemoradiotherapy;additionally,the chemoradiotherapy group had a higher proportion of patients completing≥4 chemotherapy cycle.Conclusion:This large-sample retrospective study with comprehensive datasets and long-term follow-up demonstrated comparable survival outcomes between radical chemoradiotherapy and radical surgery plus adjuvant chemotherapy for LS-SCEC.A minimum of 4 chemotherapy cycle was associated with improved prognosis.SCEC is associated with a high risk of distant metastasis and marked heterogeneity.Therefore,the treatment of LS-SCEC should prioritize an individualized approach.

In the era of immunotherapy, the advantages and limitations brought from elective nodal irradiation (ENI) needs to be re-evaluated. As immune organs, lymph nodes play a crucial role as barriers against cancer, and are involved in the activation of anti-tumor responses during radiotherapy. Numerous animal experiments have demonstrated a significant depletion of cytotoxic T cells in the tumor microenvironment, along with an increase in radiation resistance after ENI or surgical resection, leading to limited tumor regression. Furthermore, the abscopal effect stimulated by radiotherapy is markedly attenuated when ENI is combined with immunotherapy. In this article, research progress in the underlying mechanisms was reviewed.

Objective To compare the efficacy and safety of two concurrent chemoradiotherapy regimens between paclitaxel plus fluorouracil( TF) and cisplatin plus fluorouracil ( PF) in the treatment of locally advanced esophageal squamous carcinoma. Methods 103 patients with locally advanced esophagus carcinoma were treated in Affiliated Hospital of Jiangnan University from December 2014 to February 2016, and randomly assigned to either study group ( TF ) or control group ( PF ) according to random number table, of which 52 patients in the TF group while 51 patients in the PF group. The primary outcome was overall survival(OS), and secondary outcomes include progression-free survival(PFS), local progression-free survival( LPFS) and side effects. Results The 1-year OS for TF group was 76. 9％ versus 74. 5％ for PF group( P>0. 05 ) , and the 2-year OS for TF group was 59. 6％ versus 56. 9％ for PF group ( P >0. 05). The 1-year LPFS for TF group and PF group were 71. 2％ and 66. 7％ respectively(P>0. 05), and the 2-year LPFS for TF group and PF group were 61. 5％ and 58. 8％ respectively(P>0. 05). The 1-year PFS for TF group was 63. 5％ versus 62. 7％ for PF group ( P>0. 05 ) , and the 2-year PFS for TF group was 51. 9％ versus 39. 2％ for PF group ( P>0. 05 ) . The incidence rate of serious ( grade 3- 4 ) leukopenia for TF group was 36. 5％ versus 17. 6％ for PF group(χ2 =4. 642, P<0. 05). The incidence rate of serious (grade 3-4) acute radiation pneumonitis was 15. 4％ in the TF group, higher than that in the PF group with the rate of 3. 9％(χ2 =3. 859, P<0. 05), while the incidence rate of severe nausea and vomiting for PF group was 17. 6％ versus 1. 9％ for TF group(χ2 =7. 262, P <0. 05). The difference between the two groups was statistically significant. Conclusions Patients who were treated with two concurrent chemoradiotherapy regimens showed no difference in OS, PFS and LPFS. The regimen on the basis of Paclitaxel has higher risk of adverse effects incidence rates of hematological toxicity and acute radiation pneumonitis, while digestive system toxicity must be concerned when concurrent chemoradiotherapy is performed on the basis of cisplatin plus fluorouracil.

The diagnosis of local recurrence after radiochemotherapy for esophageal cancer requires the combination of multiple imaging methods (esophageal X-ray,computed tomography,endoscopic ultrasonography,and positron emission tomography-computed tomography),dynamic changes in esophagoscopy,and biopsy.The main treatment of recurrence includes salvage surgery,radiochemotherapy,endoscopic mucosal resection,and chemotherapy.The overall survival rate after the above treatment is improved compared with palliative care but still unsatisfactory.Early diagnosis of recurrence is fundamental for improved treatment outcomes.

Background and purpose:Concurrent radiochemotherapy is the standard modality for locally advanced esophageal squamous cell carcinoma (ESCC) patients. This clinical trial aimed to assess the effectiveness and toxicity of continuous infusion of 5-lfuorouracil (5-FU) and weekly paclitaxel combined with radiotherapy in ESCC patients. Methods:Patients with locally advanced (T2-4N0-1M0-1a) esophageal squamous cell carcinoma were enrolled in a prospective, single-institutional, single-arm study of deifnitive chemoradiotherapy. Patients received 61.2 Gy with IMRT in 34 fractions. Patients had a Karnofsky performance status of 70 or greater, and normal liver, renal, and bone marrow functions. Patients were recommended to receive concurrent 5-FU (300 mg/m2 civ 96 h) for 5 days a week for 5 weeks, plus paclitaxel (50 mg/m2) given during 3 hours every week for 5 weeks. Patients were recommended to receive 2 courses of consolidation chemotherapy after concurrent radio (chemo) therapy (5-FU 1 800 mg/m2 civ 72 h, plus paclitaxel 175 mg/m2 every 28 days). The primary endpoints of the study were 5 year overall survival and acute toxicity. Results:Fifty patients were enrolled in this study, including 38 male patients and 12 female patients;median age:58 years (ranged 26 to 75 years). 72%patients completed all the chemotherapy and 98%patients received the full dose of radiotherapy. 1-, 2-, 3-, and 5-year survival were 75%, 56%, 42%and 28%respectively. Among haematological toxicities, grade 3 leukopenia (16%) was recorded, and no patients experienced any≥grade 2 thrombocytopenia or anaemia. Among non-haematological toxicities, the rates of grade 2 peripheral neurotoxicity, arthralgias and myalgias, nausea, vomiting, and fatigue were 8%, 4%, 4%, 2%and 6%respectively. The rates of≥grade 2 acute radiation-induced esophageal toxicity, radiation pneumonitis and skin toxicity were 32%, 44% and 14% respectively. No treatment-related deaths occurred and no patients experienced any ≥ grade 4 toxicities. Conclusion: Continuous infusion of 5-FU plus paclitaxel given concurrently with radiotherapy may be an effective and tolerable treatment option for ESCC patients.

Background and purpose: With the increase of aging population, elderly patients (age ≥70 years) with esophageal squamous cell carcinoma occurred more and more. However, few studies have focused on elderly esophageal squamous cell carcinoma patients. This study aimed to assess the outcomes and prognostic factors for elderly patients with esophageal squamous cell carcinoma treated after deifnitive chemoradiotherapy. Methods:We retrospectively analyzed 53 patients (age≥70 years) with esophageal squamous cell carcinoma and treated with deifnitive radiotherapy with or without chemotherapy from Fudan University Shanghai Cancer Center from Mar. 2009 to Dec. 2011. Results:Median age was 74 years. Twenty-nine patients underwent radiotherapy, 24 patients underwent radiochemotherapy. 1-, 2-, 3-, and 5- year survival was 62%, 44%, 33% and 19% respectively. Grade 2 and above acute radiation-induced esophageal toxicity and radiation pneumonitis occur rate was 6% and 9% respectively. No treatment-related deaths occurred and no patients experienced any grade 4 and above toxicities. Multivariate analysis identiifed treatment modality, tumor site and smoking history as independent prognostic factors for overall survival. Conclusion:Radiotherapy may be an acceptable treatment option for elderly patients with esophageal squamous cell carcinoma. In appropriately selected patients, concurrent chemotherapy could bring a better overall survival.

Background and purpose: Alternative splicing is an important regulation mechanism of gene expression. Aberrant alternative splicing is associated with dysregulation of the cell cycle, activation of oncogenes and inactivation of the tumor suppressor genes. Thus, it is closely correlated with the pathogenesis and progression of various tumors. DNA methylation is an important part of epigenetic phenomena. Aberrant methylation of the gene promoter can result in gene silencing. Hypermethylation of tumor suppressor genes and DNA repair genes correlates with the onset of many different cancers. Additionally, DNA methylation acts as a pivotal factor for alternative splicing. Aberrant methylation disrupts the stabilization of the alternative splicing. This study investigated the promoter methylation and expression of RNA binding protein, fox-1 homolog 1 (RBFOX1) gene in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in ESCC. Methods: MassARRAY approach and RT-PCR were used respectively to examine the methylation level of RBFOX1 gene and its expression at mRNA level in tumors and corresponding adjacent normal tissues. The correlation between methylation level and clinicopathological features was analyzed. Results:RBFOX1 methylation level and mRNA expression in tumor tissues were signiifcantly lower than those in corresponding adjacent normal tissues (41.8% vs 68.3%, P<0.01). No significant correlation was observed between methylation level and clinicopathological features. The cut-off (33.6%) was calculated as the mean of the normal samples to which we applied 2.5 SD. According to the cut-off value, the object of the study was divided into two groups. The methylation level lower than the cut-off was deifned as group 1;methylation level higher than the cut-off was deifned as group 2. The 5-year overall survival rates of the two groups were 57.0%and 35.7%, respectively (P=0.06);5-year progression-free survival rates were 48.7%and 28.9%, respectively (P=0.03). However, the multivariate analysis results indicated that TNM stage was the independent factor of prognosis.Conclusion: The methylation level and mRNA expression of RBFOX1 in tumor specimens are signiifcantly lower than those in corresponding adjacent normal tissues. The methylation level of the RBFOX1 promoter is not an independent factor of prognosis.

Objective To study the effect of different dose fractionation on overall survival in patients with limited-stage small cell lung cancer (LS-SCLC). Methods LS-SCLC patients treated with radical combined chemotherapy and radiotherapy (RT) between January 2001 and Dec 2007 were analyzed retrospectively. According to the dose fractionation schemes, patients were divided into three groups:conventional fractionated RT (1. 8 -2.0 Gy,once daily), hyperfractionated RT (1.4 Gy, twice daily) and hypofractionated RT (2. 5 Gy,once daily). Overall survival, disease free survival and pattern of failures of the three groups were compared. A total of 177 patients were enrolled, including 63 patients in conventional fractionated RT group, 79 in hyperfractionated RT group and 35 in hypofractionated RT group. Results The overall follow-up rate was 96. 6%. The patient numbers with follow-up of more than 2 and 5 years were 153 and 92, respectively. The median survival time of the entire group was 22. 4 months, and the 2-and 5-year survival rates were 43.4% and 23. 5%, respectively. The 2-year survival rates for three groups were 31%, 46% and 59% (x2 =7.94,P=0.019), respectively. The 2-year disease free survival for three groups were 20%, 31% and 40% ( x2 = 4. 86, P = 0. 088 ), respectively. In the pairwise comparisons,patients in hypofractionated RT group have better survival than those in conventional fractionated RT group ( x2 = 7. 81, P = 0. 005 ), the effect of hyperfractionated RT group lies between the hypo-and the conventional fractionated RT groups, but no significant differences were detected ( x2 = 2. 31, P = 0. 128; x2 = 2. 95, P =0. 086). The mildest side effect was found in the hypofractionated RT group. No statistically significant differences were found in the patterns of first failure. Conclusion The hypofractionated RT scheme showed potential survival benefits for patients with LS-SCLC and should be considered in the setting of randomized clinical trials.

OBJECTIVETo analyse the result of late course accelerated hyper-fractionated radiotherapy (LCAHFR) of upper and middle thoracic segment esophageal T2N0M0 carcinoma.

METHODSFifty-three patients with squamous cell esophageal T2N0M0 carcinoma in the upper and middle segment were treated by LCAHFR from August 1994 to January 2000. The design of the radiation fields were based on CT and barium examination. All patients were treated with the conventional fractionated radiotherapy during the first two-thirds of the treatment to a dose about 41.4 Gy/23 F/4 to 5 weeks. This was followed by accelerated hyper-fractionated irradiation using reduced fields, twice daily at 1.5 Gy per fraction to a dose about 27 Gy/18 d. Thus, the total dose was 67-70 Gy/40-43 F/40-49 d.

RESULTSThe 1-, 2- and 5-year actuarial survival rates were 89.9%, 66.8% and 51.2%, respectively. The 1-, 2- and 5-year local control rates were 92.1%, 87.1% and 87.1%. Of the 17 patients who died, 5 died of local failure (29.4%), 9 (52.9%) of distant metastasis, 5 (29.4%) of lymph metastasis and 1 (5.9%) of bleeding from the esophagus. The Cox multivariate model showed that the site of lesion was the only prognostic factor, with upper better than the middle segment.

CONCLUSIONLate course accelerated hyper fractionated radiotherapy is one of the best radiation treatment regimen for early esophageal carcinoma in the upper and middle thoracic segment.

Aged ; Carcinoma, Squamous Cell ; radiotherapy ; Dose Fractionation ; Esophageal Neoplasms ; radiotherapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome