|
1
|
Wang M, Yang J, Wang D, Zhou J, Qin S, Jiao Y, Wang L. The role of deep hyperthermia in IMRT in elderly patients with esophageal cancer: a retrospective cohort study. Radiat Oncol 2025; 20:76. [PMID: 40375282 PMCID: PMC12083045 DOI: 10.1186/s13014-025-02661-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 05/06/2025] [Indexed: 05/18/2025] Open
Abstract
PURPOSE This study aimed to assess the clinical utility of deep hyperthermia in elderly patients with esophageal cancer(EC) who underwent intensity-modulated radiotherapy(IMRT). PATIENTS AND METHODS This retrospective analysis included 177 elderly patients with EC who underwent IMRT between 2017 and 2023, 42 of whom had combined deep hyperthermia (HT). Propensity score matching (PSM) was used to balance the covariates between the thermoradiotherapy (HTRT) group and IMRT-alone groups. Treatment outcomes and toxicities were compared between the two groups. We used the Kaplan-Meier method to estimate survival curves and the log-rank test to compare survival curves. Cox multivariate analysis was performed to analyze the prognostic factors in these patients. RESULTS After PSM (42 patients in each group), the HTRT group had a greater objective response rate (ORR) than the IMRT-alone group (83% vs. 62%, P = 0.028). The HTRT group had less radiotherapy-related toxicity, including a lower incidence of leukopenia (14% vs. 33%, P = 0.040) and RP grade ≥ 2 (P = 0.012). However, the 1-, 2-, and 3-year overall survival (OS) rates and 1-, 2-, and 3-year disease-free survival (DFS) rates were not significantly different (P = 0.730, 0.964). Grade ≥ 2 hypoproteinemia (odds ratio [OR] = 3.798, P = 0.004), radiotherapy dose ≤ 60 Gy (OR = 0.445, P = 0.006), and tumor location in the lower esophagus (OR = 0.387, P = 0.005) were adverse prognostic factors for OS. Hypoproteinemia grade ≥ 2 (OR = 3.676, P < 0.001) was also a crucial prognostic factor for DFS. CONCLUSION Adding deep hyperthermia to IMRT can improve the ORR in elderly patients with EC. In addition, it significantly reduces radiotherapy-related toxicity. Although this approach does not improve the long-term prognosis, it is still practical and has low toxicity, making it suitable for clinical use.
Collapse
Affiliation(s)
- Mengjiao Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
- Department of Radiation Oncology, Yixing Cancer Hospital, Yixing, 214200, China
| | - Jian Yang
- Department of Oncology, The Affiliated Yixing Clinical School of Medical School of Yangzhou University, Yixing, 214200, China
| | - Dafei Wang
- Department of Radiation Oncology, Yixing Cancer Hospital, Yixing, 214200, China
| | - Juying Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Songbing Qin
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Yang Jiao
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, 215123, China.
| | - Lili Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
| |
Collapse
|
|
2
|
Yang T, Fan Y, Bai G, Huang Y. RFC4 confers radioresistance of esophagus squamous cell carcinoma through regulating DNA damage response. Am J Physiol Cell Physiol 2025; 328:C367-C380. [PMID: 39672175 DOI: 10.1152/ajpcell.00533.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 11/12/2024] [Accepted: 11/18/2024] [Indexed: 12/15/2024]
Abstract
Radioresistance in esophageal squamous cell carcinoma (ESCC) is a critical factor leading to treatment failure and recurrence, yet its underlying molecular mechanisms remain unclear. This study aimed to investigate the role of replication factor C4 (RFC4) in ESCC radioresistance and to explore the underlying mechanisms. We utilized online bioinformatics tools to analyze the properties, functions, and prognostic significance of RFC4 in ESCC. We established cell lines with varying RFC4 expression levels and subjected them to radiation exposure. RFC4 expression was assessed using quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunoblotting. Cell proliferation was evaluated with MTT, 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting and immunofluorescence were used to study the impact of RFC4 on the DNA damage response in ESCC cells. A xenograft mouse model was employed to assess tumor growth in vivo. RFC4 expression was significantly upregulated in ESCC tissues and cells, particularly in radioresistant cases. Functional experiments revealed that RFC4 promotes cell proliferation, inhibits apoptosis, induces cell cycle arrest, and mitigates radiation-induced DNA damage responses. Mechanistically, RFC4-mediated radioresistance in ESCC may involve the inactivation of the p53 signaling pathway. In animal studies, RFC4 knockdown, either alone or in combination with radiation therapy, effectively suppressed the growth of xenograft tumors. These findings highlight the potential of targeting RFC4 to overcome radioresistance by modulating the DNA damage response in ESCC, offering promising therapeutic avenues for patients with ESCC.NEW & NOTEWORTHY Our research indicates that replication factor C4 (RFC4) plays a role in conferring radioresistance to esophageal squamous cell carcinoma (ESCC) by bolstering DNA damage repair, primarily through the inhibition of the p53 signaling pathway. This finding positions RFC4 as a promising therapeutic target for combating radioresistance in ESCC, although further research is required to fully comprehend its intricate role in the disease.
Collapse
Affiliation(s)
- Tao Yang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Yue Fan
- Discipline Construction Office, Baoan Central Hospital of Shenzhen, Shenzhen, China
| | - Guang Bai
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Yinpeng Huang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| |
Collapse
|
|
3
|
Xing Y, Yin Y, Yu L, Zhang C, Chai G, Lyu B, Wang B, Zhao L, Xiang G. Comparison of radiation esophagitis associated with daytime versus evening radiotherapy in patients with esophageal carcinoma. Radiat Oncol 2025; 20:3. [PMID: 39780158 PMCID: PMC11708085 DOI: 10.1186/s13014-024-02575-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
PURPOSE Based on the demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G2/M phase in the afternoon and at night, the present study evaluated the severity of acute radiation esophagitis and treatment outcomes in esophageal squamous cell carcinoma patients receiving radiotherapy (RT) in the daytime versus in the evening. METHODS From the 488 eligible patients of esophageal squamous cell carcinoma receiving concurrent chemoradiotherapy (CCRT), 369 patients received RT in the daytime (before 19:00) and 119 patients received RT in the evening (after 19:00). The grades of radiation esophagitis (Common Terminology Criteria for Adverse Events version 5.0) and survival outcomes were compared in the two groups. Analyses were performed by using ordinal logistic regression and Cox proportional hazard regression. RESULTS The median follow-up was 27 months. In multivariate logistic regression models, evening treatment (after 19:00) (odds ratio, 1.660 [95% CI 1.094-2.518]), tumor length ≥ 5 cm (odds ratio, 1.632 [95% CI 1.102-2.416]), PGTV dose ≥ 59.34 Gy (odds ratio, 1.702 [95% CI 1.099-2.635]), female sex (odds ratio, 2.241 [95% CI 1.475-3.405]), and tumor location in cervical segment and upper thoracic (odds ratio, 1.665 [95% CI 1.043-2.658]) were associated with higher odds of radiation esophagitis. There was no difference in the overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) (all p > 0.05) between the daytime treatment group and evening treatment group. The results of the subgroup analysis showed that no significant difference was found in radiation esophagitis between the two groups with PGTV dose < 59.34 Gy, while there was a higher odds for the Grade 2 or higher radiation esophagitis in the evening treatment group than the daytime treatment group (odds ratio, 1.675 [95% CI 1.062-2.643]) with PGTV dose ≥ 59.34 Gy. CONCLUSION RT in the evening (after 19:00) was associated with higher odds to present esophagitis for esophageal squamous cell carcinoma patients, especially with higher radiation doses, but treatment outcomes did not differ according to the time of RT.
Collapse
Affiliation(s)
- Yun Xing
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Yutian Yin
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Liang Yu
- Department of Information, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Cong Zhang
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Guangjin Chai
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Bo Lyu
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Bin Wang
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Lina Zhao
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China.
| | - Geng Xiang
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China.
| |
Collapse
|
|
4
|
Xiang G, Chai G, Lyu B, Li Z, Yin Y, Wang B, Pan Y, Shi M, Zhao L. Long-term results of induction chemotherapy for non-operable esophageal squamous cell carcinoma followed by concurrent chemoradiotherapy: a single-centre experience. Radiol Oncol 2024; 58:444-457. [PMID: 39287163 PMCID: PMC11406992 DOI: 10.2478/raon-2024-0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/25/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND This study aimed to investigate the long-term clinical outcomes and toxicities of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) vs. CCRT alone in patients with non-operable esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS Between 2008 and 2022, 271 ESCC patients who received definitive CCRT based on intensity modulated radiation therapy (IMRT)/volumetric modulated arc therapy (VMAT) were enrolled. Through a propensity score-matched (PSM) method, 71 patients receiving IC and CCRT were matched 1:1 to patients who received CCRT alone. The Kaplan-Meier method and Cox proportional hazards model were applied to analyze survival and prognosis. RESULTS The IC + CCRT group had no improvement in 5-year overall survival (OS) rate, recurrence-free survival (RFS) rate, and distant metastasis-free survival (DMFS) rate (all p > 0.05) compared with the CCRT group. The 5-year OS rate (65.6% vs. 17.6% vs. 29.3%, p < 0.001), RFS rate (65.6% vs. 17.6% vs. 26.9%, p < 0.001), and DMFS rate (62.5% vs. 10.3% vs. 27.2%, p < 0.001) of the IC good responders were significantly higher than that of the IC poor responders and CCRT group. Multivariate analysis revealed that total radiotherapy time (≥ 49 days) and stage III/IV were independent predictive factors of OS, RFS, and DMFS. No significant differences were observed in the rates of grade 3-4 toxicities between both groups. CONCLUSIONS Our results showed the addition of IC to CCRT was not superior to CCRT in unselected ESCC patients, while IC responders could benefit from this regime without an increase in toxicities.
Collapse
Affiliation(s)
- Geng Xiang
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Guangjin Chai
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Bo Lyu
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Zhaohui Li
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Yutian Yin
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Bin Wang
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Yanglin Pan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Mei Shi
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Lina Zhao
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| |
Collapse
|
|
5
|
Wang H, Li Y, Qiu M, Wang J. Thrombocytopenia and hyperprogression after radiotherapy and camrelizumab treatment in an esophageal cancer patient with increased JAK2 gene copies: a case report. Front Oncol 2024; 14:1283428. [PMID: 38974233 PMCID: PMC11224440 DOI: 10.3389/fonc.2024.1283428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 05/30/2024] [Indexed: 07/09/2024] Open
Abstract
Radiotherapy (RT) and immune checkpoint inhibitor (ICI) are important treatments for esophageal cancer. Some studies have confirmed the safety and effectiveness of using RT in combination with ICI, while serious side effects have been exhibited by some patients. We report a patient with metastatic esophageal cancer who received RT combined with ICI. The patient experienced severe thrombocytopenia, and treatment with thrombopoietin and corticosteroids were ineffective. Finally, the patient developed abscopal hyperprogression outside the radiation field. Interestingly, next-generation sequencing revealed increased JAK2 gene copies in the surgical slices. The JAK2/STAT3 pathway is involved in the regulation of megakaryocyte development. Recurrent thrombocytopenia may activate the JAK2/STAT3 pathway, leading to megakaryocyte differentiation and platelet biogenesis. However, persistent activation of the JAK2/STAT3 pathway has been associated with immune ICI resistance and tumor progression. This case indicates that thrombocytopenia and increased JAK2 gene copies may be risk factors for poor prognosis after ICI and RT treatment.
Collapse
Affiliation(s)
- Hang Wang
- Department of Endocrinology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China
- Department of Cardiology, Hospital of Traditional Chinese Medicine in Qijiang District, Chongqing, China
| | - Yun Li
- Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang, Neijiang, Sichuan, China
| | - Min Qiu
- Department of Oncology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
| | - Jianmin Wang
- Department of Oncology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
| |
Collapse
|
|
6
|
Li C, Chang X, Wang Q, Pang Q, Xiao Z, Zhang W, Yuan Z. Two distinct age-prognosis patterns in patients with esophageal cancer undergoing surgical and radiotherapy treatments: a combined analysis of 3JECROG and SEER databases. Ther Adv Med Oncol 2024; 16:17588359241261009. [PMID: 38882446 PMCID: PMC11179523 DOI: 10.1177/17588359241261009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 05/24/2024] [Indexed: 06/18/2024] Open
Abstract
Background Age is a known prognostic factor for various cancers. However, few studies explored the association between age and prognosis of esophageal cancer (EC) comprehensively, especially from a nonlinear perspective. Design Retrospective cohort study. Objectives Our study aims to explore the possible nonlinear associations between age and prognosis in EC patients receiving curative surgery and radiotherapy, respectively. Methods Cox regression models with restricted cubic splines were used to model the possible nonlinear relationship between age and prognosis in surgical and radiotherapy groups, respectively. Surveillance, Epidemiology, and End Results database was used to validate the age-prognosis patterns found in Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group database. Age-prognosis patterns were further validated by survival comparisons between different age subgroups and in subsequent sensitivity and subgroup analyses. Primary endpoint is overall survival. Secondary endpoints are cancer-specific survival and progression-free survival. Results A total of 56,457 patients from two large cancer databases were included. Patients receiving surgery and radiotherapy showed two distinct nonlinear age-prognosis patterns. Age showed a U-/J-shaped association with prognosis in the radiotherapy group, with a nadir at approximately 65- to 70-years-old. As for surgical cohort, relative risk for all-cause mortality and cancer-specific mortality increased with age with p for nonlinearity <0.05. The above age-prognosis relationships were validated by sensitivity, subgroup, and comparative survival analyses. Youngest and middle-aged patients showed better survival results compared to that of other age subgroups in surgical and radiotherapy cohorts, respectively [Radiotherapy, youngest/middle: hazard ratio (HR) = 1.06, 95% confidence interval (CI): 1.02-1.10, p = 0.001; Radiotherapy, oldest/middle: HR = 1.21, 95% CI: 1.18-1.24, p < 0.001; Surgical, middle/youngest: HR = 1.19, 95% CI: 1.14-1.25, p < 0.001; surgical, oldest/youngest: HR = 1.85, 95% CI: 1.75-1.97, p < 0.001]. Conclusion Patients receiving surgery and radiotherapy showed two distinct age-prognosis patterns. Younger and middle-aged patients were associated with better survival in surgical and radiotherapy groups, respectively. Additional studies are warranted to explore the underlying mechanisms and clinical implications of this phenomenon.
Collapse
Affiliation(s)
- Chen Li
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Xiao Chang
- Department of Radiation Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Beijing Institute for Cancer Research, Beijing, China
| | - Qifeng Wang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qingsong Pang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Zefen Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wencheng Zhang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, West Huan-Hu Road, Ti Yuan Bei, Hexi District, Tianjin 300060, China
| | - Zhiyong Yuan
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, West Huan-Hu Road, Ti Yuan Bei, Hexi District, Tianjin 300060, China
| |
Collapse
|
|
7
|
Wang L, Liu L, Cao Y, Chen X, Liu S, Li X, Han J, Wang Q, Han C. Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II clinical trial. BMC Cancer 2024; 24:679. [PMID: 38831450 PMCID: PMC11149230 DOI: 10.1186/s12885-024-12427-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/24/2024] [Indexed: 06/05/2024] Open
Abstract
OBJECTIVE To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). METHODS Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. RESULTS (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4-5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. CONCLUSIONS The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).
Collapse
Affiliation(s)
- Lan Wang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China
| | - Lihong Liu
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China
| | - Yu Cao
- Anti-Cancer Association of Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaoxi Chen
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China
| | - Shutang Liu
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China
| | - Xiaoning Li
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China
| | - Jing Han
- Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Qi Wang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China
| | - Chun Han
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
| |
Collapse
|
|
8
|
Gao LR, Zhang J, Huang N, Deng W, Ni W, Xiao Z, Liu M. Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2024; 25:6082. [PMID: 38892269 PMCID: PMC11172887 DOI: 10.3390/ijms25116082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/24/2024] [Accepted: 05/26/2024] [Indexed: 06/21/2024] Open
Abstract
We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.
Collapse
Affiliation(s)
- Lin-Rui Gao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (L.-R.G.); (W.D.); (W.N.)
| | - Jiajun Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (J.Z.); (N.H.)
| | - Ning Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (J.Z.); (N.H.)
| | - Wei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (L.-R.G.); (W.D.); (W.N.)
| | - Wenjie Ni
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (L.-R.G.); (W.D.); (W.N.)
| | - Zefen Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (L.-R.G.); (W.D.); (W.N.)
| | - Mei Liu
- Laboratory of Cell and Molecular Biology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| |
Collapse
|
|
9
|
Li ZM, Liu W, Chen XL, Wu WZ, Xu XE, Chu MY, Yu SX, Li EM, Huang HC, Xu LY. Construction and validation of classification models for predicting the response to concurrent chemo-radiotherapy of patients with esophageal squamous cell carcinoma based on multi-omics data. Clin Res Hepatol Gastroenterol 2024; 48:102318. [PMID: 38471582 DOI: 10.1016/j.clinre.2024.102318] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 03/05/2024] [Accepted: 03/09/2024] [Indexed: 03/14/2024]
Abstract
BACKGROUND Concurrent chemo-radiotherapy (CCRT) is the preferred non-surgical treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Unfortunately, some patients respond poorly, which leads to inappropriate or excessive treatment and affects patient survival. To accurately predict the response of ESCC patients to CCRT, we developed classification models based on the clinical, serum proteomic and radiomic data. METHODS A total of 138 ESCC patients receiving CCRT were enrolled in this study and randomly split into a training cohort (n = 92) and a test cohort (n = 46). All patients were classified into either complete response (CR) or incomplete response (non-CR) groups according to RECIST1.1. Radiomic features were extracted by 3Dslicer. Serum proteomic data was obtained by Olink proximity extension assay. The logistic regression model with elastic-net penalty and the R-package "rms" v6.2-0 were applied to construct classification and nomogram models, respectively. The area under the receiver operating characteristic curves (AUC) was used to evaluate the predictive performance of the models. RESULTS Seven classification models based on multi-omics data were constructed, of which Model-COR, which integrates five clinical, five serum proteomic, and seven radiomic features, achieved the best predictive performance on the test cohort (AUC = 0.8357, 95 % CI: 0.7158-0.9556). Meanwhile, patients predicted to be CR by Model-COR showed significantly longer overall survival than those predicted to be non-CR in both cohorts (Log-rank P = 0.0014 and 0.027, respectively). Furthermore, two nomogram models based on multi-omics data also performed well in predicting response to CCRT (AUC = 0.8398 and 0.8483, respectively). CONCLUSION We developed and validated a multi-omics based classification model and two nomogram models for predicting the response of ESCC patients to CCRT, which achieved the best prediction performance by integrating clinical, serum Olink proteomic, and radiomic data. These models could be useful for personalized treatment decisions and more precise clinical radiotherapy and chemotherapy for ESCC patients.
Collapse
Affiliation(s)
- Zhi-Mao Li
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China; Department of Radiation Oncology, Shantou Central Hospital, Shantou 515041, Guangdong, PR China
| | - Wei Liu
- College of Science, Heilongjiang Institute of Technology, Harbin 150050, Heilongjiang, PR China
| | - Xu-Li Chen
- Department of Clinical Laboratory Medicine, Shantou Central Hospital, Shantou 515041, Guangdong, PR China
| | - Wen-Zhi Wu
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China
| | - Xiu-E Xu
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China
| | - Man-Yu Chu
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China
| | - Shuai-Xia Yu
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China
| | - En-Min Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, PR China
| | - He-Cheng Huang
- Department of Radiation Oncology, Shantou Central Hospital, Shantou 515041, Guangdong, PR China.
| | - Li-Yan Xu
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China.
| |
Collapse
|
|
10
|
Liou Y, Lan TL, Lan CC. A Meta-Analysis and Review of Radiation Dose Escalation in Definitive Radiation Therapy between Squamous Cell Carcinoma and Adenocarcinoma of Esophageal Cancer. Cancers (Basel) 2024; 16:658. [PMID: 38339409 PMCID: PMC10854668 DOI: 10.3390/cancers16030658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 01/30/2024] [Accepted: 02/02/2024] [Indexed: 02/12/2024] Open
Abstract
Esophageal cancer, ranked as the eighth most prevalent cancer globally, is characterized by a low survival rate and poor prognosis. Concurrent chemoradiation therapy (CCRT) is the standard therapy in the non-surgical treatment of localized carcinoma of the esophagus. Nevertheless, the radiation doses employed in CCRT remain notably lower compared to the curative definite chemoradiation therapy utilized in the management of other carcinomas. In order to increase the local control rates and enhance the treatment outcomes, several clinical trials have used high-dose radiation to analyze the effect of dose escalation. Despite the integration of technically advanced RT schemes such as intensity-modulated radiation therapy (IMRT), the results of these trials have failed to demonstrate a significant improvement in overall survival or local progression-free survival. In this review, we investigated previous clinical trials to determine the ineffectiveness of radiation dose escalation in the context of CCRT for esophageal cancer. We aim to clarify the factors contributing to the limited efficacy of escalated radiation doses in improving patient outcomes. Furthermore, we delve into recent research endeavors, exploring prospective radiation dose modifications being altered based on the histological characteristics of the carcinoma. The exploration of these recent studies not only sheds light on potential refinements to the existing treatment protocols but also seeks to identify novel approaches that may pave the way for more efficacious and personalized therapeutic strategies for esophageal cancer management.
Collapse
Affiliation(s)
- Yu Liou
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei City 112, Taiwan
| | - Tien-Li Lan
- Department of Heavy Particles and Radiation Oncology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City 112, Taiwan
| | - Chin-Chun Lan
- Thoracic Surgery Group, Clinical Research Center, Department of Surgery, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua City 500, Taiwan
- Department of Emergency and Critical Care Medicine, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua City 500, Taiwan
- Post-Baccalaureate Medical School, National Chung Hsing University, 145 Xingda Rd., South District, Taichung City 402, Taiwan
| |
Collapse
|
|
11
|
Wang FM, Mo P, Yan X, Lin XY, Fu ZC. Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy. World J Gastrointest Oncol 2024; 16:1-7. [PMID: 38292836 PMCID: PMC10824118 DOI: 10.4251/wjgo.v16.i1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 11/14/2023] [Accepted: 12/06/2023] [Indexed: 01/11/2024] Open
Abstract
Four major studies (Checkmate577, Keynote-590, Checkmate649 and Attraction-4) of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy, represented by anti-programmed death protein (PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer, from the aspects of proof of concept, long-term survival, overall survival rate and progression-free survival. For unresectable or inoperable nonmetastatic esophageal cancer, concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines. Because its curative effect is still not ideal, it is necessary to explore radical radiotherapy and chemotherapy in the future, and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1. This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.
Collapse
Affiliation(s)
- Feng-Mei Wang
- Department of Obstetrics and Gynecology, Fuzong Clinical Medical College (900th Hospital), Fujian Medical University, Fuzhou 350025, Fujian Province, China
- Department of Obstetrics and Gynecology, Dongfang Hospital, Xiamen University, Fuzhou 350025, Fujian Province, China
| | - Peng Mo
- Department of Radiotherapy, Fuzong Clinical Medical College (900th Hospital), Fujian Medical University, Fuzhou 350025, Fujian Province, China
| | - Xue Yan
- Department of Radiotherapy, Fuzong Clinical Medical College (900th Hospital), Fujian Medical University, Fuzhou 350025, Fujian Province, China
| | - Xin-Yue Lin
- Department of Radiotherapy, Fuzong Clinical Medical College (900th Hospital), Fujian Medical University, Fuzhou 350025, Fujian Province, China
| | - Zhi-Chao Fu
- Department of Radiotherapy, Fuzong Clinical Medical College (900th Hospital), Fujian Medical University, Fuzhou 350025, Fujian Province, China
- Department of Radiotherapy, Dongfang Hospital, Xiamen University, Fuzhou 350025, Fujian Province, China
| |
Collapse
|
|
12
|
Deng W, Chang X, Dong X, Zhao Y, Yang D, Jiang L, Shi A, Yu H, Yu R, Xiao Z, Wang W. Induction immunochemotherapy followed by radiotherapy for patients with unresectable locally advanced or metastatic esophageal cancer: A propensity score-matched analysis. Int Immunopharmacol 2023; 124:110955. [PMID: 37725845 DOI: 10.1016/j.intimp.2023.110955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND The study aimed to investigate the efficacy of induction immunochemotherapy before radiotherapy (RT) for patients with locally advanced or metastatic esophageal cancer. METHODS Patients with unresectable locally advanced or metastatic esophageal cancer who received induction immunochemotherapy followed by RT (ICIs + RT group) and RT alone (RT group) were retrospectively identified in two cancer centers, respectively. Propensity score matching (PSM) was used to balance the potential confounders between the two groups. Overall survival (OS), progression-free survival (PFS), and recurrence patterns were evaluated. RESULTS A total of 467 patients were reviewed, and 66 were matched in each group. After PSM, the 1- and 2-year OS rates were 84.6% and 57.9% in ICIs + RT group, and 71.1% and 43.0% in RT group (HR 0.60, 95% CI 0.36-1.00, p = 0.050). The absolute increase of restricted mean survival time (RMST) for OS in ICIs + RT group compared with RT group were 0.89 years (p = 0.023) at one year and 2.59 years at two years (p = 0.030). The median PFS time, 1- and 2-year PFS rates were 20.3 months, 69.3%, and 45.7% in ICIs + RT group, and 12.2 months, 51.4%, and 35.8% in RT group (HR 0.64, 95% CI 0.41-0.99, p = 0.045). The cumulative locoregional recurrence (LRR) rate was significantly lower in ICIs + RT group (1-year rate, 17.4% vs. 38.8%, p = 0.011), and distant metastasis (DM) rates were comparable (p = 0.755). Consolidation ICIs was associated with a trend of improved 1-year OS and PFS. CONCLUSION Induction immunochemotherapy followed by RT might improve locoregional control and survival outcomes for patients with unresectable locally advanced or metastatic esophageal cancer.
Collapse
Affiliation(s)
- Wei Deng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xiao Chang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xin Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yuting Zhao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Dan Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Leilei Jiang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Anhui Shi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Huiming Yu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Rong Yu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zefen Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
| | - Weihu Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
| |
Collapse
|
|
13
|
Lin Y, Liang HW, Liu Y, Pan XB. Nivolumab adjuvant therapy for esophageal cancer: a review based on subgroup analysis of CheckMate 577 trial. Front Immunol 2023; 14:1264912. [PMID: 37860010 PMCID: PMC10582756 DOI: 10.3389/fimmu.2023.1264912] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 09/18/2023] [Indexed: 10/21/2023] Open
Abstract
Esophageal cancer is the sixth most common cancer worldwide. Approximately 50% of patients have locally advanced disease. The CROSS and NEOCRTEC5010 trials have demonstrated that neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for patients with resectable disease. However, a pathological complete response is frequently not achieved, and most patients have a poor prognosis. The CheckMate 577 trial demonstrates that nivolumab adjuvant therapy improves disease-free survival in patents without a pathological complete response. However, there are still numerous clinical questions of concern that remain controversial based on the results of the subgroup analysis. In this review, we aim to offer constructive suggestions addressing the clinical concerns raised in the CheckMate 577 trial.
Collapse
Affiliation(s)
- Yan Lin
- Department of Gastroenterology, Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
| | - Huan-Wei Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Yang Liu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Xin-Bin Pan
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| |
Collapse
|
|
14
|
Wu XQ, Zhang TY, Yang F, Feng XY, Feng YL, Wang LL, Chen TW, Li CP, Li R. Association of radiotherapy with thoracic vertebral fractures in esophageal squamous cell carcinoma: A retrospective cohort study. Medicine (Baltimore) 2023; 102:e35304. [PMID: 37773852 PMCID: PMC10545250 DOI: 10.1097/md.0000000000035304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 08/30/2023] [Indexed: 10/01/2023] Open
Abstract
To investigate the association between radiotherapy (RT) and thoracic vertebral fractures in esophageal squamous cell carcinoma (ESCC) and explore the risk factors of thoracic vertebral fracture in ESCC who underwent RT. This retrospective cohort study including 602 consecutive ESCC patients examined the association between RT and thoracic vertebral fractures using multivariable Cox proportional hazard models and relevant risk factors of thoracic vertebral fractures based on clinical and RT parameters in patients with ESCC. Followed for a median follow-up of 24 months, 54 patients had thoracic vertebral fractures. The multivariable analysis revealed RT as an independent risk factor after adjusting for clinical risk factors. Univariable analyses associated a 5-Gy increase in vertebral dose to single vertebrae and a 1-time increase in RT fraction with higher risk of vertebral fracture. Adding RT factors (vertebral dose and fraction) and mean vertebral hounsfield unit to the Cox models containing conventional clinical risk factors significantly improved the χ2 value for predicting vertebral fractures (all P < .001). This study revealed RT, as well as increased vertebral dose and RT fractions, as a significant, consistent, and strong vertebral fracture predictor in ESCC. Combined vertebral dose, RT fractions, and vertebral hounsfield unit provided optimal risk stratification for ESCC patients.
Collapse
Affiliation(s)
- Xing-Qiang Wu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
- Department of Radiology, The second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tian-Yue Zhang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
| | - Fan Yang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
| | - Xin-Yi Feng
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
| | - Yu-Ling Feng
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
| | - Ling-Li Wang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
| | - Tian-Wu Chen
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
| | - Chun-Ping Li
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
| | - Rui Li
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, and Sichuan Key Laboratory of Medical Imaging, Sichuan, China
| |
Collapse
|
|
15
|
Wang X, Han W, Zhang W, Wang X, Ge X, Lin Y, Zhou H, Hu M, Wang W, Liu K, Lu J, Qie S, Zhang J, Deng W, Wang L, Han C, Li M, Zhang K, Li L, Wang Q, Shi H, Yu Z, Zhao Y, Sun X, Shi Y, Pang Q, Zhou Z, Liang J, Chen D, Feng Q, Bi N, Zhang T, Deng L, Wang W, Liu W, Wang J, Zhai Y, Wang J, Chen W, Chen J, Xiao Z. Effectiveness of S-1-Based Chemoradiotherapy in Patients 70 Years and Older With Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Netw Open 2023; 6:e2312625. [PMID: 37195667 PMCID: PMC10193185 DOI: 10.1001/jamanetworkopen.2023.12625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 03/21/2023] [Indexed: 05/18/2023] Open
Abstract
IMPORTANCE Double-agent intravenous chemotherapy concurrent with radiotherapy is the standard of care for patients with inoperable esophageal cancer. However, patients tend to tolerate intravenous chemotherapy less well with age and comorbidities. It is essential to find a better treatment modality that improves survival outcomes without reducing the quality of life. OBJECTIVE To evaluate the effectiveness of simultaneous integrated boost radiotherapy (SIB-RT) with concurrent and consolidated oral S-1 chemotherapy for patients aged 70 years and older with inoperable esophageal squamous cell carcinoma (ESCC). DESIGN, SETTING, AND PARTICIPANTS This multicenter, phase III randomized clinical trial was conducted between March 2017 and April 2020 in 10 centers in China. Patients with inoperable, locally advanced, clinical stage II to IV ESCC were enrolled and randomized to receive SIB-RT concurrent with and followed by oral S-1 chemotherapy (CRTCT group) or SIB-RT alone (RT group). Data analysis was completed on March 22, 2022. INTERVENTIONS In both groups, the planning gross tumor volume was administered with radiation dose of 59.92 Gy and the planning target volume was administered with radiation dose of 50.4 Gy, in 28 fractions each. In the CRTCT group, concurrent S-1 was administered on radiotherapy days, and consolidated S-1 was administered at 4 to 8 weeks after SIB-RT. MAIN OUTCOMES AND MEASURES The primary end point was overall survival (OS) of the intent-to-treat population. Secondary end points were progression-free survival (PFS) and toxicity profile. RESULTS A total of 330 patients (median [IQR] age, 75.5 [72-79] years; 220 [66.7%] male patients) were included, with 146 patients randomized to the RT group and 184 randomized to the CRTCT group. A total of 107 patients (73.3%) in the RT group and 121 patients (67.9%) in the CRTCT group were clinically diagnosed with stage III to IV disease. At the time of analysis of the 330 patients in the intent-to treat-population (March 22, 2022), OS was improved in the CRTCT group compared with the RT group at 1 year (72.2% vs 62.3%) and 3 years (46.2% vs 33.9%; log-rank P = .02). PFS was similarly improved in the CRTCT group compared with the RT group at 1 year (60.8% vs 49.3%) and 3 years (37.3% vs 27.9%; log-rank P = .04). There was no significant difference in the incidence of treatment-related toxic effects higher than grade 3 between the 2 groups. Grade 5 toxic effects occurred in each group, including 1 patient who experienced myelosuppression and 4 patients with pneumonitis in the RT group and 3 patients with pneumonitis and 2 patients with fever in the CRTCT group. CONCLUSIONS AND RELEVANCE These findings suggest that oral S-1 chemotherapy administered with SIB-RT should be considered as an alternative treatment option for patients aged 70 years and older with inoperable ESCC, since it improved survival outcomes without additional treatment-related toxic effects compared with SIB-RT alone. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02979691.
Collapse
Affiliation(s)
- Xin Wang
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiming Han
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wencheng Zhang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Xiaomin Wang
- Department of Radiation Oncology, Anyang Cancer Hospital, Anyang, China
| | - Xiaolin Ge
- Department of Radiation Oncology, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Yu Lin
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Haiwen Zhou
- Department of Radiation Oncology, Anyang Cancer Hospital, Anyang, China
| | - Miaomiao Hu
- Department of Oncology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Wei Wang
- Department of Oncology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Ke Liu
- Department of Radiation Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jianchao Lu
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China
| | - Shuai Qie
- Department of Radiation Oncology, Affiliated Hospital of Hebei University, Baoding, China
| | - Jihong Zhang
- Department of Radiation Oncology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Wei Deng
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
| | - Lan Wang
- Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Chun Han
- Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Minghe Li
- Department of Radiation Oncology, Anyang Cancer Hospital, Anyang, China
| | - Kaixian Zhang
- Department of Oncology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Ling Li
- Department of Oncology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Qifeng Wang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China
| | - Hongyun Shi
- Department of Radiation Oncology, Affiliated Hospital of Hebei University, Baoding, China
| | - Zhilong Yu
- Department of Radiation Oncology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Yidian Zhao
- Department of Radiation Oncology, Anyang Cancer Hospital, Anyang, China
| | - Xinchen Sun
- Department of Radiation Oncology, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Yonggang Shi
- Department of Radiation Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qingsong Pang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Zongmei Zhou
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Liang
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dongfu Chen
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qinfu Feng
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tao Zhang
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei Deng
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenqing Wang
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenyang Liu
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianyang Wang
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yirui Zhai
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Junjie Wang
- Department of Radiation Oncology, Peking University Third Hospital, Beijing, China
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Junqiang Chen
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Zefen Xiao
- Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
16
|
Han W, Wang L, Li C, Chen J, Zhang W, Wang X, Pang Q, Zhao Y, Sun X, Zhang K, Li G, Li L, Qiao X, Liu M, Wang Y, Deng L, Wang W, Bi N, Zhang T, Deng W, Ni W, Chang X, Zhou Z, Liang J, Feng Q, Wang L, Chen D, Lv J, Zhu S, Han C, Xiao Z. Progression-free survival as surrogate endpoint of overall survival in esophageal squamous cell carcinoma: a real-world data and literature-based analysis. Ther Adv Med Oncol 2022; 14:17588359221131526. [PMID: 36324733 PMCID: PMC9619262 DOI: 10.1177/17588359221131526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 09/22/2022] [Indexed: 11/06/2022] Open
Abstract
Background The surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal squamous cell carcinoma (ESCC) remains unelucidated. This study aimed to determine the validity of PFS as a surrogate endpoint for OS in ESCC patients treated with definitive radiotherapy or definitive chemoradiotherapy (dRT/dCRT), as well as characterize the prognostic factors and survival of such patients. Methods A total of 3662 patients from 10 cancer centers were enrolled. One-, 2-, and 3-year PFS (PFS12, PFS24, and PSF36, respectively) were used as time points for analysis. At each time point, ESCC-specific mortality and OS were characterized using competing risk and conditional survival models, while correlation between PFS and OS was evaluated by linear regression. Results At PFS12, PFS24, and PFS36, a progressive decrease in 5-year ESCC-specific mortality (35.2%-13.4%) and increase in 5-year OS (46.6%-62.9%) were observed. Regardless, the OS of patients remained markedly lower than those of the age- and sex-matched Chinese general population. TNM stage remained a significant prognostic factor at PFS36. Strong correlation was found between 3-year PFS and 5-year OS, which was further externally validated. Conclusions Three-year PFS may act as a potential surrogate endpoint for 5-year OS. TNM stage was considered a significant prognostic factor for OS, and may represent the optimal prognostic tool to guide clinical decision-making and post-treatment follow-up.
Collapse
Affiliation(s)
| | | | - Chen Li
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center for Cancer, Tianjin, China
| | - Junqiang Chen
- Department of Radiation Oncology, Fujian Cancer Hospital/Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Wencheng Zhang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center for Cancer, Tianjin, China
| | - Xin Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qingsong Pang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center for Cancer, Tianjin, China
| | - Yidian Zhao
- Department of Radiation Oncology, Anyang Cancer Hospital, Anyang, China
| | - Xinchen Sun
- Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Kaixian Zhang
- Department of Oncology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Gaofeng Li
- Department of Radiation Oncology, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Ling Li
- Department of Oncology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Xueying Qiao
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Miaoling Liu
- Department of Radiation Oncology, Affiliated Hospital of Hebei University, Baoding, China
| | - Yadi Wang
- Department of Radiation Oncology, PLA Army General Hospital, Beijing, China
| | - Lei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenqing Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tao Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Deng
- Department of Radiation Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Beijing Institute for Cancer Research, Beijing, P.R. China
| | - Wenjie Ni
- Department of Radiation Oncology, Beijing Shijitan Hospital, Capital Medical University, Ninth School of Clinical Medicine, Peking University, School of Oncology, Capital Medical University, Beijing, P.R. China
| | - Xiao Chang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zongmei Zhou
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Liang
- Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Hospital, Shenzhen, China
| | - Qinfu Feng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lvhua Wang
- Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Hospital, Shenzhen, China
| | - Dongfu Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jima Lv
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuchai Zhu
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Chun Han
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, No.12, Health Road, Shijiazhuang, Hebei, China
| | | |
Collapse
|
|
17
|
Radiation Dose-Effect Relation in Patients with Esophageal Squamous Cell Carcinoma: A National Cancer Center Data and Literature-Based Analysis. JOURNAL OF ONCOLOGY 2022; 2022:2438270. [PMID: 36317125 PMCID: PMC9617729 DOI: 10.1155/2022/2438270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 10/03/2022] [Indexed: 11/28/2022]
Abstract
Introduction Despite receiving definitive chemoradiotherapy (dCRT) with radiation dose (RTD) of 50.4 Gy, survival of esophageal carcinoma was dismal. The effect of RTD in cancer control and radiotoxicity, and the extent to which local-regional control (LRC) influenced survival remain vague. This study aimed at evaluating RTD-effect relationship in esophageal squamous cell carcinoma (ESCC). Methods 1440 dRT/CRT-treated ESCC patients were enrolled. Restricted cubic spline regression model was applied to reveal nonlinear relationship between RTD and survival/radiotoxicity. Linear regression analysis (LRA) was performed to evaluate correlations between LRC and overall survival (OS) or progression-free survival (PFS). Results For 1440 dRT/CRT-treated ESCC patients, with RTD escalating, hazard ratios (HRs) of OS, PFS, LRC declined until RTD exceeded 60 Gy, then increased. HR of treatment-related mortality was stable until RTD exceeded 60 Gy, then increased. HR of LRC was lower for majority of patients treated with RTD≥60 Gy, except for those with KPS<80, T1-2 lesion, or without lymph node metastasis. LRA revealed strong correlations between LRC and OS/PFS. 45.5% and 44.9% of OS and PFS improvements were owing to improved LRC. Conclusions RTD of 60 Gy was well tolerated, with favorable survival resulted of LRC improvement in local-advanced ESCC. Further stratification analyses based on radiation sensitivity will be helpful to determine potential beneficiaries of RTD escalation.
Collapse
|
|
18
|
Yang H, Wang K, Li Y, Li S, Yuan L, Ge H. Local Ablative Treatment Improves Survival in ESCC Patients With Specific Metastases, 2010–2016: A Population-Based SEER Analysis. Front Oncol 2022; 12:783752. [PMID: 35785182 PMCID: PMC9243329 DOI: 10.3389/fonc.2022.783752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 05/16/2022] [Indexed: 11/17/2022] Open
Abstract
Background We aimed to explore the role of local ablative treatment (LAT) in metastatic esophageal squamous cell cancer (ESCC) patients who received chemotherapy and identify patients who will most likely benefit. Methods We analyzed data of metastatic ESCC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The chi-square test was used to evaluate the unadjusted clinicopathological categorical variables between the two groups. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors of overall survival. Propensity score matching (PSM) was used to adjust the differences between the two groups. Results Overall, 720 metastatic ESCC patients treated with chemotherapy were analyzed in this study; 63.2% of patients (n = 455) received LAT, including radiotherapy (n = 444), primary site surgery (n = 12), or lymph node dissection (n = 27). Gender (HR = 1.220, 95% CI: 1.024–1.453, p = 0.026), bone metastases (HR = 1.559, 95% CI: 1.292–1.882, p < 0.001), and liver metastases (HR = 1.457, 95% CI: 1.237–1.716, p < 0.001) were independent prognostic factors in the entire population. However, LAT was not an independent prognostic factor. Further subgroup analyses showed that LAT improved OS from 8.0 months to 10.0 months in patients with metastases other than bone/liver (HR = 0.759, 95% CI: 0.600–0.961, p = 0.022). LAT was not a prognostic factor in patients with bone/liver metastases (HR = 0.995, 95% CI: 0.799–1.239, p = 0.961). After PSM, the median OS was 8.0 months (95% CI: 7.2–8.8 months) and patients who received LAT had a better OS than patients without LAT (HR = 0.796, 95% CI: 0.653–0.968, p = 0.023). Patients with metastases other than bone/liver could benefit from LAT compared with those with bone/liver metastases. Conclusions Our study indicated that metastatic ESCC patients with metastases other than bone/liver could derive additional benefit from LAT with systemic chemotherapy.
Collapse
Affiliation(s)
| | | | | | | | - Ling Yuan
- *Correspondence: Ling Yuan, ; Hong Ge,
| | - Hong Ge
- *Correspondence: Ling Yuan, ; Hong Ge,
| |
Collapse
|
|
19
|
Gao LR, Li C, Han W, Ni W, Deng W, Tan L, Zhou Z, Chen D, Feng Q, Liang J, Lv J, Wang W, Liu W, Deng L, Wang X, Zhang T, Wang J, Zhai Y, Bi N, Wang L, Hui Z, Li YX, Xiao Z. Survival benefit of surgery in patients with clinical T4 esophageal cancer who achieved complete or partial response after neoadjuvant chemoradiotherapy or radiotherapy. Ther Adv Med Oncol 2022; 14:17588359221108693. [PMID: 35923925 PMCID: PMC9340417 DOI: 10.1177/17588359221108693] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 06/06/2022] [Indexed: 11/26/2022] Open
Abstract
Objective: This study aimed to determine the long-term survival of patients with cT4
esophageal cancer (EC) and whether neoadjuvant
chemoradiotherapy/radiotherapy plus surgery (nCRT/RT + S) is superior to
definitive CRT(dCRT)/RT in terms of survival in cT4 EC downstaged after
nCRT/RT. Summary background data: Treatment options for cT4 EC include dCRT/RT and nCRT/RT + S, but it is not
clear whether the latter provides survival benefit in patients downstaged
after nCRT/RT. Methods: From 2002 to 2017, 726 patients with cT4 esophageal squamous cell carcinoma
(ESCC) were retrospectively analyzed. Patients achieving clinical complete
response (cCR) or partial response (PR) after 4-week RT (median dose,
40.7 Gy) and considered fit for surgery were offered esophagectomy. Of the
726 patients, 308 (42.4%) achieved cCR/PR, while 74 patients received
subsequent surgery (nCRT/RT + S group), 234 patients received dCRT/RT. Results: Median follow-up was 58 months. The 3-year overall survival (OS) and
progression-free survival (PFS) rates for all patients were 33.3% and 35.6%,
respectively. The corresponding OS and PFS rates were 54.8% and 48.5% in the
nCRT/RT + S group versus 30.0% and 22.1% in the dCRT/RT
group (both p < 0.0001). After adjusting the confounding
variables with inverse probability of treatment weighting, the adjusted
3-year OS rates were 50.4% in the nCRT/RT + S group versus
50.8% in the dCRT/RT group (p = 0.15). However, the
adjusted 3-year PFS rates were significantly different between the two
groups (49.0% and versus 38.3%,
p = 0.004). Postoperative complications occurred in 18
(24.3%) patients. Conclusion: The long-term survival of cT4 ESCC was improved after the use of
three-dimensional CRT. In cT4, EC responded to nCRT/RT, surgery improves PFS
but not OS.
Collapse
Affiliation(s)
- Lin-Rui Gao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chen Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiming Han
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenjie Ni
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lijun Tan
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zongmei Zhou
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dongfu Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qinfu Feng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Liang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jima Lv
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenqing Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenyang Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tao Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianyang Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yirui Zhai
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lvhua Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhouguang Hui
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ye-Xiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Road, Chaoyang District, Beijing 100021, China
| | - Zefen Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Road, Chaoyang District, Beijing 100021, China
| |
Collapse
|
|
20
|
Zhang X, Wang T, Xiao X, Li X, Wang CY, Huang B, He L, Song Y. Radiotherapy for head and neck tumours using an oral fixation and parameter acquisition device and TOMO technology: a randomised controlled study. BMJ Open 2021; 11:e052542. [PMID: 34772753 PMCID: PMC8593711 DOI: 10.1136/bmjopen-2021-052542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 10/19/2021] [Indexed: 11/08/2022] Open
Abstract
INTRODUCTION Radiotherapy has become one of the main methods used for the treatment of malignant tumours of the head and neck. Spiral tomographic intensity-modulated radiotherapy has the many advantages of precision radiotherapy, which puts forward high requirements for postural reproducibility and accuracy. We will aim to ensure that the accurate positioning of the tumour will reduce the side effects of radiotherapy caused by positioning errors. We will design and implement this clinical trial using the patent of 'a radiotherapy oral fixation and parameter acquisition device (patent number: ZL201921877986.5)'. METHODS AND ANALYSIS This will be a randomised, controlled, prospective study with 120 patients with head and neck tumours. Using the random number table method, a random number sequence will be generated, and the patients will be enrolled in the experimental group (oral fixation device) and the control group (conventional fixation) in a 2:1 ratio. The primary outcome will be the progression-free survival time after the treatment. Secondary outcomes will include the oral mucosal reaction and the quality of life. Follow-ups will be carried out according to the plan. This is V.1.0 of protocol on 1 April 2021. The recruitment process for this clinical trial commenced on 1 May 2021, and will end on 1 October 2022. ETHICS AND DISSEMINATION The trial received ethical approval from Medical Ethics Committee of Liaoning Provincial Cancer Hospital (number 20210131X). The final results will be presented at a scientific conference and published in a peer-reviewed journal in accordance with the journal's guidelines. TRIAL REGISTRATION NUMBER ChiCTR2100045096.
Collapse
Affiliation(s)
- Xiaofang Zhang
- Department of Radiotherapy, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| | - Tianlu Wang
- Department of Radiotherapy, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xinyan Xiao
- China Medical University, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xia Li
- Department of Radiotherapy, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| | - Chen Yu Wang
- Department of Information Management, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| | - Bo Huang
- Department of Pathology, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| | - Lei He
- Department of Radiotherapy Physics, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yingqiu Song
- Department of Radiotherapy, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| |
Collapse
|