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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.
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Objective:To analyze whether involved-field irradiation (IFI) was associated with improved survival and reduced treatment-related adverse events compared with elective nodal irradiation (ENI) in Chinese patients with esophageal squamous cell carcinoma receiving radiotherapy.Methods:Literature review was conducted from CNKI, Wanfang Data, PubMed, Embase, Web of Science and Cochrane Central databases (until July 31, 2022). Relevant data were collected according to the inclusion and exclusion criteria. Primary outcomes included overall survival (OS) rate and treatment-related adverse events. Secondary outcomes included progression-free survival (PFS) rate and local control rate (LCR). Risk of bias was assessed using the Cochrane Risk of Bias tool. The quality of the results was assessed by using the meta analysis of Evidence Evaluation and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methods.Results:A total of 7 articles with 918 patients were included of which 465 received IFI and 453 received ENI. The 1-, 2-, 3-and 5-year OS rates in the IFI group were not significantly different from those in the ENI group (1-year OS rate: RR=1.00, 95% CI=0.94-1.07, P=0.97, high certainty; 2-year OS rate: RR=1.01, 95% CI=0.90-1.13, P=0.90, high certainty; 3-year OS rate: RR=0.86, 95% CI=0.71-1.05, P=0.14, high certainty; 5-year OS rate: RR=0.76, 95% CI=0.42-1.37, P=0.36, low certainty). In the IFI group, patients with ≥grade 2 acute radiation esophagitis ( RR=0.71, 95% CI=0.58-0.87, P=0.001, high certainty), ≥grade 3 acute radiation esophagitis ( RR=0.39, 95% CI=0.24-0.64, P<0.001, high certainty) and ≥grade 2 acute radiation pneumonitis ( RR=0.72, 95% CI=0.52-0.99, P=0.04, high certainty) were significantly lower compared with those in the ENI group. However, no significant differences were observed in the incidence of ≥grade 3 late radiation esophagitis, ≥grade 3 acute radiation pneumonitis and ≥grade 3 late radiation pneumonitis between two groups. No significant differences were noted in the 1-, 2-, 3-PFS rates and LCR between two groups. Conclusions:For Chinese patients with esophageal squamous cell carcinoma, IFI and ENI yield similar efficacy in terms of OS, PFS and LCR. However, IFI has a lower incidence of ≥grade 2 acute radiation esophagitis, ≥grade 3 acute radiation esophagitis and ≥grade 2 acute radiation pneumonitis than ENI.
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Objective:To compare the efficacy and prognosis of elective nodal irradiation (ENI) combined with nedaplatin chemotherapy and involved field irradiation (IFI) combined with nedaplatin chemotherapy in the radical radiotherapy treatment of patients with cervical or upper thoracic esophageal cancer.Methods:Seventy-eight patients with cervical or upper thoracic esophageal cancer in Hai'an Traditional Chinese Medicine Hospital from February 2017 to February 2020 were selected and divided into ENI group and IFI group according to random number table method, with 39 cases in each group. The ENI group was treated with ENI combined with nedaplatin chemotherapy, while the IFI group was treated with IFI combined with nedaplatin chemotherapy. After 2 months of treatment, the therapeutic effect and the dose of lung irradiation were compared between the two groups, and the occurrence of adverse reactions and prognosis were compared.Results:The total effective rate and disease control rate were 69.23% (27/39) and 82.05% (32/39) in IFI group, and 64.10% (25/39) and 74.36% (29/39) in ENI group, there was no significant difference between the two groups ( χ2 = 0.23, P = 0.631; χ2 = 0.68, P = 0.411). The lung irradiation doses of V 5 Gy and V 20 Gy in IFI group were lower than those in ENI group (both P < 0.05). The incidence rates of bone marrow suppression and radiation lung injury in IFI group were lower than those in ENI group (all P < 0.05). By the end of follow-up, the survival rates of IFI group and ENI group were 76.92% (30/39) and 66.67% (26/39), respectively. There was no significant difference in overall survival between the two groups ( χ2 = 1.06, P = 0.300). Conclusions:ENI and IFI combined with nedaplatin chemotherapy in the radical radiotherapy treatment of cervical and upper thoracic esophageal cancer have similar efficacy and prognosis, but IFI can reduce the lung radiation dose and the incidence of adverse reactions.
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Objective:To explore the efficacy of elective nodal irradiation (ENI) and involved field irradiation (IFI) combined with chemotherapy in treatment of esophageal cancer.Methods:A total of 104 patients with esophageal cancer in Affiliated Hospital of Jiangnan University from May 2018 to May 2020 were selected as subjects for prospective study. All patients were randomly divided into observation group and control group by lottery method with 52 cases in each group. The target volume of observation group was delineated with IFI, and the control group was delineated with ENI. The curative effects, the levels of serum tumor markers [carbohydrate antigen 50 (CA50), squamous cell carcinoma (SCC) and carcinoembryonic antigen (CEA)] before and after treatment, the 1-year overall survival (OS) rate, the incidence of adverse reactions and the scores of various dimensions of health survey summary (SF-36) after treatment were compared between the two groups.Results:The total effective rate in the observation group was 90.38% (47/52), the total effective rate in the control group was 84.62% (44/52), and the difference was not statistically significant ( χ2 = 0.79, P =0.374). There was no statistical difference in CA50, CEA, SCC levels between the two groups before and after treatment (all P > 0.05). After treatment, the CA50, CEA and SCC levels in the two groups were lower than those before treatment, and the differences were statistically significant (all P < 0.05). The 1-year OS rate of the observation group was 94.23%, the control group was 90.38%, and the difference in OS between the two groups was not statistically significant ( χ2 = 0.54, P = 0.462). The incidence of acute radiation esophagitis in the observation group was lower than that in the control group, and the difference was statistically significant ( P < 0.001). There was no statistical difference between the two groups in SF-36 scale scores of physical functioning, role-physical, bodily pain, mental health, vitality, social functioning, role-emotional, and general health after treatment (all P > 0.05). Conclusions:Both ENI and IFI are effective treatments for patients with esophageal cancer. There is no significant difference in the quality of life of patients between the two delineation methods, but the incidence of acute radiation esophagitis is lower in patients with IFI regimen.
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Objective:To explore the benefit groups of patients with locoregional recurrence of esophageal thoracic squamous cell carcinoma who received radiotherapy or chemoradiotherapy with different patterns of irradiation.Methods:Clinical data of 344 esophageal thoracic squamous cell carcinoma patients with postoperative recurrence who received intensity conformal radiotherapy or concurrent chemoradiotherapy in the Fourth Hospital of Hebei Medical University from 2009 to 2014 were retrospectively analyzed. The distribution of recurrence sites and prognostic factors were analyzed. A stratified analysis was carried out on the benefit groups of patients receiving the elective nodal irradiation (ENI) and involved field irradiation (IFI).Results:276 cases (80.2%) recurred at a single site and 68 cases (19.8%) recurred at more than two sites. The follow-up rate was 96.2%. The 1-, 3-and 5-year overall survival rates were 53.6%, 22.6% and 16.4%, respectively, with a median of 12.8 months (95% CI: 11.3-14.3 months). The 1-, 3-and 5-year local recurrence-free survival rates were 46.5%, 16.9% and 12.0%, respectively, with a median of 11.0 months (95% CI: 9.6-12.4 months). The 1-, 3-and 5-year progression-free survival rates were 39.8%, 11.3% and 6.7%, respectively, with a median of 7.9 months (95% CI: 5.8-10.0 months). Multivariate analysis showed that gender, the log odds of metastatic lymph nodes (LODDS) and the number of chemotherapy cycles were the independent prognostic factors ( P=0.003, <0.001, <0.001). Subgroup univariate analysis demonstrated that patients with an esophageal lesion length<5.0 cm, N 0 stage, the number of surgically-dissected lymph nodes of ≤9, the number of postoperative positive lymph node metastasis site of 0, and LODDS≤0.030 obtained benefits from ENI ( P=0.032, 0.012, 0.001, 0.012 and 0.014). Patients with the number of surgically-dissected lymph nodes of ≥16 achieved benefits from IFI ( P=0.035). Conclusions:Radiotherapy is an effective treatment mode for patients with local recurrence after esophageal cancer surgery. For patients with preoperative esophagography showing shorter esophageal lesions, earlier postoperative pathological N stage, lower LODDS score, and fewer surgically-dissected lymph nodes probably obtain more benefits from ENI than IFI. However, patients with more surgically-dissected lymph nodes may obtain more benefit from IFI compared with ENI.
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Objective To investigate the prognostic effects and failure patterns of different clinical target volumes of IMRT in definitive chemoradiotherapy for cervical and upper-thoracic esophageal cancer,in order to provide a reference for radiotherapy target area delineation.Methods A retrospective analysis was performed on the clinical data of 132 patients with cervical and upper-thoracic esophageal cancer who received definitive IMRT and concurrent chemotherapy in our hospital from 2010 to 2014.Seventy-one patients received elective nodal irradiation (ENI) and the other 61 patients received involvedfield irradiation (IFI).The Kaplan-Meier method was used to calculate local control (LC),progressionfree survival (PFS) and overall survival (OS) rates.The significant difference was evaluated by the logrank test.The prognostic factors were determined by Cox univariate and multivariate analyses.Results The last follow-up time was December 2017,the median follow-up time was 59.5 (14.2-95.8) months.Follow-up rate was 99.2％.For the ENI and IFI groups,the 1-,3-,5-year LC were 77.5％,58.8％,48.8％ vs.64.3％,29.1％,26.2％ (x2=9.68,P=0.002),PFS were 68.6％,37.7％,25.9％ vs.47.5％,17.2％,3.6％ (x2=11.39,P=0.001),OS were 81.7％,53.9％,31.3％ vs.70.5％,31.9％,16.3％ (x2=7.70,P =0.006),respectively.In multivariate analysis,T stage,N stage,and RT field were independent factors for LC,PFS and OS(P＜0.05).The total failure rates,local-regional recurrent rate in ENI group were lower than those in IFI group (x2 =13.23,5.24,P＜0.05).No significant differences were found in acute radiation esophagitis,pneumonitis and myelosuppression (Grades ≥ 3) between the two groups(P＞0.05).Conclusions Compared with IFI,ENI can significantly reduce local-regional recurrence and distant metastasis and improve the long-term survival for cervical and upper-thoracic esophageal cancer patients who received definitive chemoradiotherapy.
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Objective To explore the clinical efficacy of lymph node involved-field irradiation (IFI) and elective nodal irradiation (ENI) for treatment of esophageal cancer among Asian populations. Methods The randomized controlled trials and retrospective analyses of Asian esophageal cancer patients treated by IFI and ENI were retrieved by computer in Cochrane Library, PubMed, Embase, CNKI, and Wanfang database. The last retrieval time was May 2018. According to the inclusion and exclusion criteria, the clinical efficacy, adverse reactions and failure modes were selected in each study. A Meta-analysis was performed by using Review Manager 5.3 software to compare the advantages and disadvantages of IFI group and ENI group in treatment of Asian esophageal cancer patients. Results Eventually, a total of 18 domestic and foreign literature that meet the standards (6 randomized controlled trials, 12 retrospective analyses) were included, with a total of 2220 patients. There were no significant differences in the overall survival rate, the local control rate, the local/regional failure rate, the distant metastasis rate, the intra-field recurrence rate, and the field recurrence rate between the IFI group and the ENI group (all P>0.05). The overall failure rate of ENI group was slightly lower than that of IFI group (P= 0.05). The incidence of radiation pneumonitis in ENI group was higher than that in IFI group (P= 0.004), and the incidence of radiation esophagitis was higher than that in IFI group (P< 0.01). Conclusion For Asian patients with esophageal cancer, ENI has no obvious advantage compared with IFI, including the increase of adverse reactions.
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Objective To observe the curative effect,failure pattern and treatment-related toxicities of elective nodal irradiation (ENI) and involved field irradiation (IFI) in patients with thoracic esophageal squamous cell carcinoma treated with radical radiotherapy, and determine the reasonable target delineation of radiotherapy. Methods Using prospective randomized controlled design, a total of 86 patients with thoracic esophageal squamous cell carcinoma were randomly allocated to two groups:ENI group(n=39)and IFI group(n=47).Both groups received concurrent chemoradiotherapy.In ENI group,the high-risk lymphatic drainage area received prophylactic irradiation on the basis of IFI group.After the treatment, all patients were followed up for 3~33 months.The median follow-up period was 15 months.The short-term effective rate, one year survival rate, progression free survival rate and the local control rate of two groups were calculated. The survival curve was drawn by the Kaplan-Meier method,and the survival rate was compared using the Log-rank method.Meanwhile, the treatment failure pattern and incidence of adverse reactions were analyzed in the two groups. Results There was no significant difference in effective rate between ENI group and IFI group (92.3% vs. 95.7%,χ 2=0.460, P>0.05). The one-year survival rates were 66.7% and 68.1% for the two groups,respectively.The progression-free survival rates were 56.4% and 53.2% respectively.The local control rates were 92.3% and 87.5% respectively,with no statistical difference(P>0.05). The median survival time was 15 months at the end of the follow-up for group ENI and group IFI, and there was no significant difference in survival rate between two groups(Log-rank χ2=1.520,P=0.218).There were 35 cases with treatment failure in all 86 patients, of which 17 cases were in group ENI and 18 cases in group IFI. The regional failure rates were 35.9% and 27.7% in ENI and IFI groups respectively,distant metastasis rates were 20.5% and 14.9% respectively,in-field failure rates were 30.8% and 23.4% respectively, and out-of-field failure rates were 4.3% and 5.1% respectively, which showed no significant differences (P>0.05). There were no significant differences in side effects, the incidence of bone marrow suppression,gastrointestinal reactions,radiation esophagitis and radiation-induced lung injury between two groups (P>0.05). Conclusion ENI shows similar recent efficacy, failure patterns, adverse reactions and prognosis with IFI for thoracic esophageal squamous cell carcinoma patients receiving radical radiotherapy. So IFI treatment is recommended to minimize the exposure dosage of normal tissue.
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Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.
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Objective:To compare the therapeutic effects by different longitude margins of the gross tumor volume (GTV) based on elec-tive nodal irradiation (ENI) and to investigate the optimization of clinical tumor volume (CTV) in the radical chemoradiotherapy of esophageal squamous cell carcinoma (ESCC). Methods:ESCC patients treated with chemoradiotherapy for the first time in the First Af-filiated Hospital of Xiamen University from May 2009 to November 2012 were retrospectively studied. All patients were treated with ENI for radical radiotherapy, and the patients were divided into two groups:CTV1 group (with longitudinal external expansion length of less than 3 cm) and CTV2 group (with longitudinal external expansion length of more than 3 cm). The survival time and occurrence of side effects in patients were compared. Results:Among the 142 cases of patients, 82 and 61 cases were classified under CTV1 and CTV2, respectively. No significant difference in the overall survival (OS) and local recurrence-free survival (LRFS) rates was observed af-ter 1, 3, and 5 years of treatment between the two groups. The occurrence of side effects, such as bone marrow suppression, radiation pneumonitis, radiation esophagitis, and esophageal fistula, was less than 5%in both groups, and the data show that the side effect oc-currence in CTV1 was significantly lower. Conclusion:In the radical chemoradiotherapy of esophageal cancer using ENI, the OS rate of patients with a delineated CTV according to a 3 cm GTV longitudinal external expansion length is not lower than that of patients with a delineated CTV according to a GTV longitudinal external expansion length of more than 3 cm. The results provide a reference for the optimization of CTV in the radical chemoradiotherapy of ESCC.
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Objective To assess the outcomes of involved field irradiation (IFI) and elective nodal irradiation (ENI) in patients older than 70 years with esophageal squamous-cell carcinoma(SCC) receiving radical IMRT,and to determine whether IFI is feasible in these patients.Methods Totally 79 patients older than 70 years diagnosed with SCC of esophagus without distant metastases were collected.48 patients were received IFI,and the other 31 patients were treated with ENI.With a median follow-up time of 24 months,disease-free survival,overall survival,patterns of failure,irradiated lung dose and radiation pneumonitis were observed and compared between IFI and ENI groups.Results In IFI and ENI arm,the disease-free survival rates of 1,2,3 years were 60.4％,34.9％,29.7％ and 64.5％,54.0％,35.0％,respectively(P ＞0.05).The 1-,2-,and 3-year survival rates were 72.9％,43.4％,31.5％ for the IFI arm,and 73.0％,53.0％,38.3％ for the ENI arm(P ＞ 0.05).The ENI arm had a tendency to expand survival,but the two arms had no significant difference (P ＞ 0.05).The patterns of failure also had no difference between the two arms.Distant failure,local failure,uninvolved nodal failure in IFI arm were 22.9％,27.0％,4.2％,while in ENI arm were 25.8％,0,19.4％,all of them had no significant difference (P ＞ 0.05).However,the lung V5,V20,mean lung dose in ENI arm were higher than that in IFI and all of them had a significantly difference (t =4.66,29.90,15.63,P ＜ 0.05).The radiation pneumonitis rates were higher in ENI than in IFI arm.The rates of degree 1-2 and degree 3 were 22％,19％,and 13％ and 4％ in the two arms,respectively,with a significantly difference(x2 =4.55,4.77,P ＜ 0.05).Conclusions It is feasible that IFI for definitive IMRT in the elderly patients older than 70 years with SCC,because it got similar disease-free survival and overall survival but with less lung doses along with decreased radio-pulmonary lesion when compared with ENI.
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Objective To investigate the value of prophylactic irradiation to the lymphatic drainage area in radical three-dimensional conformal radiotherapy (3DCRT) and to evaluate the efficacy and adverse effects of 3DCRT with different clinical target volumes.Methods A retrospective analysis was performed on the records of 219 esophageal cancer patients without distant metastasis who received 3DCRT from January 2005 to December 2010.One hundred and five patients received involved-field irradiation (IFI) with a total dose of 54-66 Gy;114 patients received elective nodal irradiation (ENI) with a total dose of 46-52 Gy; the prescribed dose to the primary lesion was 56-70 Gy.The Kaplan-Meier method was used to calculate local control (LC) and overall survival (OS) rates,and the log-rank test was used for univariate prognostic analysis.Results The 1-,3-,and 5-year sample sizes were 219,172 and 67,respectively.The 1-,3-,and 5-year LC rates for IFI group were 63.0％,39.1％,and 27.2％,respectively,versus 70.5％,53.3％,and 51.7％ for ENI group (x2 =6.22,P =0.013) ;the 1-,3-,and 5-year OS rates for IFI group were 67.6％,24.9％,and 15.0％,respectively,versus 73.7％,45.1％,and 26.0％ for ENI group (x2=5.04,P =0.025).The univariate stratified analysis showed that the LC and OS rates were significantly higher in the ENI group than in the IFI group for patients with middle-or lower-thoracic primary lesion or N0 disease (P=0.007,0.015;P=0.054,0.013).Conclusions For esophageal cancer patients with middle-or lower-thoracic primary lesion or without lymph node metastasis,prophylactic irradiation to the lymphatic drainage area can increase LC and OS rates.
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Objective: This study was performed to analyze the feasibility of elective nodal irradiation (ENI) for early-stage esophageal carcinoma (EEC), evaluate the curative effect of radiation therapy for EEC, and determine the causes of treatment failure. Methods:Data were collected from 123 patients with esophageal squamous cell carcinoma of clinical T1-2 N0-1 M0 stage. Patients were divided into two groups based on different types of radiation therapy. Among the 123 patients, 102 underwent involved field irradiation (IFI), whereas 21 received ENI. A comparative analysis of patients in the two groups was conducted. Results:In 123 patients, the one-, three-, and five-year overall survival rates were 87.8%, 47.2%, and 36.6%, respectively. By contrast, the one-, three-, and five-year local control rates were 89.4%, 67.5%, and 48.8%, respectively. After comparing the one-, three-, and five-year survival rates in the ENI patients (i.e., 90.5%, 47.6%, and 42.9%, respectively) with those in the IFI patients (i.e., 86.3%, 49.0%, and 35.2%, respectively), no significant difference was found (χ2=0.290, P=0.588 8). The results indicate that ENI possibly decreased nodal metastases (χ2=5.778, P=0.016). Conclusion:Three-dimensional conformal radiotherapy is one of the best therapeutic regimens of radiation for EEC. ENI is possibly effective for preventing regional nodal metastasis. Whether ENI leads to an improved overall survival needs further investigation.
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PURPOSE: To investigate the effectiveness and safety of definitive radiation therapy for Stage I non-small cell lung cancer patients who were medically inoperable or refused surgery. Material and M ethods: A retrospective study was conducted of 36 patients who received definitive radiation therapy for pathologically proven Stage I non-small cell lung cancer in the Department of Radiation Oncology, Asan Medical Center, between July 1989 and July 2003. Twenty three patients received conventional radiation therapy with a fraction size of 1.2~3.0 Gy, with a total dose of 50.0~70.2 Gy (CRT group). Thirteen patients received stereotactic radiosurgery with a fraction size of 10~12 Gy, with a total dose of 30~48 Gy using a Stereotactic Body Frame (Precision TherapyTM, SRS group). RESULTS: The two- and 5-year overall survival rates (OS) of all the patients were 79 and 44%, respectively. The two- and 5-year OS of the CRT and SRS groups were 43 and 53%, and 7 and 27%, respectively, but showed no statistically significant difference (p=0.5173). The two- and 5-year cause-specific survival rates (CSS) of the SRS group were superior to those of the CRT group (2YCSS: 100 vs. 70%, 5YCSS: 50 vs. 39%), but were not statistically significant (p=0.2086). The two- and 5-year local progressionfree survival rates (LPFS) of all the patients were 67 and 57%, respectively. The 5-year LPFS of the SRS group was superior to that of the CRT group (66 vs. 54%), but was not statistically significant (p=0.3937). The T-stage, tumor size, treatment method (CRT vs. SRS) and tumor dose did not affect the 2-year LPFS. Grade 2~3 radiation pneumonitis developed in 5 patients (14%), all in the CRT group. The omission of elective nodal irradiation (ENI) did not affect the incidence of Grade 2~3 radiation pneumonitis in the CRT group (ENI group 17%, no ENI group 25%, p=0.538). CONCLUSION: Definitive radiation therapy for Stage I non-small cell lung cancer patients that were medically inoperable or who refused surgery was considered effective and safe. Stereotactic radiosurgery was proven to be superior to that of conventional radiation therapy, although no statistically significant difference was shown. To investigate the optimal radiation dose and fractionation scheme of SRS, a prospective study, including more patients, is mandatory