| Part Ⅰ Utilization trend and comparison of different radiotherapy modes for patients with early-stage endometrial cancer:a nationwide multicenter retrospective studyPurpose:The criteria of patients with high-intermediate(HIR)early-stage endometrial cancer are inconsistent.In addition,the adjuvant radiation recommendations for HIR patients remain controversial.This study aims to compare the outcomes of different radiation modalities among patients who met HIR criteria of GOG 249,PORTEC-2,and ESTRO-ESMO-ESGO,respectively based on the multicentric real-world data over 15 years.Methods:Patients diagnosed with FIGO Ⅰ-Ⅱ endometrial cancer between 2000-2015 in 13 Chinese medical institutes and treated with hysterectomy and radiotherapy(RT)were enrolled.All of the enrolled patients were reclassified into HIR groups according to the HIR criterion of GOG 249,PORTEC-2,and ESTRO-ESMO-ESGO,respectively.The utilization trend of different RT modes based on the real-world data during the periods was reviewed.Survival outcomes and toxicities were compared between the EBRT±VBT and VBT alone in each HIR group.Results:A total of 1038 patients were reviewed.Among them,473 patients met the HIR criteria of GOG 249,184 met the criteria of PORTEC-2,and 204 patients were reclassified into the ESMO-ESGO-ESTRO cohort.The utilization trend of VBT alone showed a significant increase from 2002 to 2015(Man-Kendall trend test,P<0.05).While the utilization rate of EBRT+VBT declined to around 25%in 2015(Man-Kendall trend test,P>0.05).And the utilization rate of EBRT alone decreased until 2005 and slowly raised to the level of about 25%from 2005 to 2015(P>0.05).Survival analyses showed that there were no significant differences in OS,DFS,LRFS,and DMFS between VBT alone and EBRT ± VBT in three HIR cohorts.Subgroup analysis in the GOG249 cohort revealed that EBRT±VBT had higher 5-year DFS,DMFS,LRFS than VBT alone for patients who did not undergo lymph node dissection,(P<0.05).The 5-year DFS of EBRT group was significantly higher than that of VBT group(93%vs 62.3%,P=0.049).The 5-year LRFS in EBRT group was significantly higher than that in VBT group(96.20%vs 72.80%,P=0.044).After balancing other risk factors by propensityscore matching(PSM),there were still significant differences in DFS and LRFS between the two RT groups(P<0.05).EBRT± VBT had a significantly higher rate of acute and late radiation-induced toxicities than VBT alone(P<0.05).Conclusion:According to the HIR criteria defined by GOG-249,PORTEC-2,and ESMO-ESGO-ESTRO,the use of VBT alone in the three groups of HIR patients showed a significant upward trend,but some patients still received EBRT.For early highintermediate-risk patients,EBRT did not improve survival outcomes compared with VBT alone,but toxicities were significantly increased.Pelvic EBRT performed postoperatively improved DFS and LRFS in patients who did not undergo lymph node dissection in highor high-intermediate risk patients as defined by the GOG-249 trial.Part Ⅱ Recurrent patterns after postoperative radiotherapy for early-stage endometrial cancer:A competing risk analysis modelPurpose:The study aimed to evaluate site-specific recurrent patterns via competing risks analysis and hazard function to provide evidence for adjuvant treatment and follow-up for early staged endometrial cancer(EC).Methods:A total of 858 patients with FIGO stage Ⅰ-Ⅱ EC who received adjuvant radiotherapy at our institution(2000-2017)were included.The radiotherapy modality comprised external beam radiotherapy(EBRT)with or without vaginal brachytherapy(VBT)or VBT alone.Competing risks analysis and hazard rate function was employed to evaluate the recurrence rate according to the ESMO-ESGO-ESTRO risk classification.Results:The five-year overall survival rates of the low risk(LR),intermediate-risk(IR),high-intermediate risk(HIR),and high risk(HR)groups were 96.1%,95%,93%,and 89.7%,respectively(P=0.018).68 patients developed recurrences.The five-year incidence of distant recurrence was the highest in the HR group(14.87%),followed by the HIR(7.71%),IR(5.27%),and LR(1.26%)groups(Gray’s test,P<0.001).The LR and IR groups showed late metastasis behaviors for distant metastasis.The HR group presented a large magnitude of distant metastasis with an early peak that increased beyond three years.Subgroup analysis revealed that EBRT±VBT tended to reduce the locoregional relapse rate compared with VBT in the HIR-HR group(2.36%vs 7.73%,Gray’s test,P=0.08).Conclusion:The established competing risk modeling demonstrated different recurrence patterns across the risk groups and radiotherapy modes.A better understanding of the change of site-specific recurrence behavior allows more targeted adjuvant treatment and surveillance regimens.Part Ⅲ Recurrence Features And Factors Influencing Post-relapse Survival In Early-stage Endometrial Cancer After Adjuvant RadiotherapyPurpose:To evaluate the recurrent patterns and effect of al factors on survival after recurrence(R-OS)in early stage endometrial cancer(EC).Methods:Patients with FIGO stage Ⅰ-Ⅱ EC,who underwent post-surgery radiotherapy(RT)at our institution between 2000 and 2017,were enrolled.First recurrent patterns,overall survival(OS),and R-OS were evaluated.Univariate and multivariate analyses(MVA)were used to evaluate factors associated with R-OS.Results:756 patients were analyzed including 510 patients who received vaginal brachytherapy(VBT)and 246 patients who received external beam radiotherapy(EBRT)± VBT,of whom 66 patients experienced recurrence,including 21 locoregional relapses and 45 distant metastases.Outside RT field recurrence predominated intra-RT field recurrence(106 versus 10 lesions).The 5-year OS rates for patients with and without recurrence were 62.2%and 98.2%,respectively(P<0.001).Among patients who underwent previous VBT,the 5-year OS rates were 61.1%,92.3%,and 99.1%for distant metastasis,locoregional relapse,and non-recurrence,respectively(P<0.001);among patients who received EBRT ± VBT,the 5-year OS rates were 51.4%,50.0%,and 98.3%,respectively(P<0.001).On Cox MVA of R-OS for locoregional recurrence patients,paraaortic lymph node metastasis was associated with poorer R-OS(hazard ratio[HR]10.047,P=0.039),and salvage RT was superior to other therapies(HR 0.06,P=0.026).On Cox MVA of R-OS for distant metastasis,patients with brain metastasis(P=0.041)had the worst R-OS and patients benefited most from combined therapy(HR 0.02,P=0.001).Conclusion:Recurrent patterns were dominated by outside RT field and distant metastasis for early-stage ECs after adjuvant RT.The modality of prior RT had an impact on the choice of salvage therapy.RT could still be an effective salvage treatment for patients who develop locoregional recurrence.Patients with distant metastasis may benefit more from combined therapies. |
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