Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response ...Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.展开更多
Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptos...Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.展开更多
Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in Nationa...Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site.Results: In the 1,085 patients, 679(62.6%) cases were nodal DLBCL(N-DLBCL) and 406 cases(37.4%) were extranodal DLBCL(EN-DLBCL). The most common sites of N-DLBCL were lymphonodus(64.8%), Waldeyer's ring(19.7%), mediastinum(12.8%) and spleen(2.7%), while in EN-DLBCL, stomach(22.4%), intestine(16.0%),nose and sinuses(8.9%), testis(8.4%), skin(7.9%), thyroid(6.9%), central nervous system(CNS)(6.4%), breast(5.7%), bone(3.4%), and salivary gland(2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival(OS) rate and progression-free survival(PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9%(P=0.008), and the 5-year PFS were57.0% and 49.0%(P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate(83.6%) and PFS rate(76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach,breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%,respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%.Conclusions: In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.展开更多
Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determ...Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 cohort that received definitive surgery for early disease.Method：From January 2008 to December 2013,449 consecutive patients with rectal cancer were treated and their outcome maintained in a database.Patients with LARC underwent total mesorectal excision（TME）surgery at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I group pertains to patients whose initially limited disease was not upstaged after TME surgery alone.After propensity score matching（PSM）,comparisons of local regional control（LC）,distant metastasis-free survival（DMFS）,disease-free survival（DFS）and overall survival（OS）were performed using Kaplan-Meier analysis and log-rank test between yp I and p I groups.Down-staging depth score（DDS）,a novel method of evaluating CRT response,was used for subset analysis.Results：Of the 449 patients,168 matched cases were generated for analysis.Five-year LC,DMFS,DFS and OS for stage p I vs.yp I groups were 96.7%vs.96.4%（P=0.796）,92.7%vs.73.6%（P=0.025）,91.2%vs.73.6%（P=0.080）and 93.1%vs.72.3%（P=0.040）,respectively.In the DDS-favorable subset of the yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,respectively）.Conclusions：LC was comparable in both groups;however,distant metastasis developed more frequently in down-staged LARC than de novo early stage cases,reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response.DDS can be an indicator to identify a subset of the yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.展开更多
Objective:The predictive effect of preoperative chemoradiotherapy(CRT)is low and difficult in guiding individualized treatment.We examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer...Objective:The predictive effect of preoperative chemoradiotherapy(CRT)is low and difficult in guiding individualized treatment.We examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative CRT.Methods:From April 2012 to April 2019,95 patients with locally advanced gastric cancer who received preoperative concurrent CRT and who were enrolled in three prospective studies were included.All patients were stage T_(3/4) N_(+).Local control,distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)were evaluated.Clinicopathological factors related to long-term prognosis were analyzed using univariate and multivariate analyses.The down-staging depth score(DDS),which is a novel method of evaluating CRT response,was used to predict long-term outcomes.Results:The median follow-up period for survivors was 30 months.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve predicted by the DDS was 0.728,which was better than the pathological complete response(pCR),histological response and ypN0.Decision curve analysis further affirmed that DDS had the largest net benefit.The DDS cut-off value was 4.pCR and ypN0 were associated with OS(P=0.026 and 0.049).Surgery and DDS are correlated with DMFS,DFS and OS(surgery:P=0.001,<0.001 and<0.001,respectively;and DDS:P=0.009,0.013 and 0.032,respectively).Multivariate analysis showed that DDS was an independent prognostic factor of DFS(P=0.021).Conclusions:DDS is a simple,short-term indicator that was a better surrogate endpoint than pCR,histological response and ypN0 for DFS.展开更多
Background: Magnetic resonance(MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation(UHF-WPRT)is a novel approach to radiotherapy for patients with high-risk(HR)and very high-risk(VHR)prostate c...Background: Magnetic resonance(MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation(UHF-WPRT)is a novel approach to radiotherapy for patients with high-risk(HR)and very high-risk(VHR)prostate cancer(PCa).However,the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time.We aimed to estimate the delivered dose,study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods: Ten patients with clinical stage T3a-4N0-1M0-1c PCa,who consecutively received UHF-WPRT,were enrolled prospectively.The contours of the target and organ-at-risks on the position verification-MR(PV-MR),beam-on 3D-MR(Bn-MR),and post-MR(after radiotherapy delivery)were derived from the pre-MR data by deformable image registration.The physician then manually adjusted them,and dose recalculation was performed accordingly.GraphPad Prism 9(GraphPad Prism Software Inc.)was utilized for conducting statistical analyses.Results: In total,we collected 188 MR scans(50 pre-MR,50 PV-MR,44 Bn-MR,and 44 post-MR scans).With median 59 min,the mean prostate clinical target volume(CTV)-V_(100%)was 98.59%±2.74%,and the mean pelvic CTVp-V_(100%)relative percentages of all scans was 99.60%±1.18%.The median V29 Gy change in the rectal wall was−2%(−18%to 20%).With a median follow-up of 9 months,no patient had acute Common Terminology Criteria for Adverse Events(CTCAE)grade 2 or more severe genitourinary(GU)or gastrointestinal(GI)toxicities(0%).Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape(ATS)workflow was technically feasible for patients with HR and VHR PCa,presenting only mild GU and GI toxicities.The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis.Clinical trial registration Chinese Clinical Trial Registry ChiCTR2000033382.展开更多
Background Rituximab combined with cyclophosphamide,doxorubicin hydrochloride,vincristine,and prednisone(R-CHOP)regimen has improved the survival of diffuse large B-cell lymphoma(DLBCL)patients worldwide,compared with...Background Rituximab combined with cyclophosphamide,doxorubicin hydrochloride,vincristine,and prednisone(R-CHOP)regimen has improved the survival of diffuse large B-cell lymphoma(DLBCL)patients worldwide,compared with CHOP alone.Several limitations were seen in previous studies of Chinese DLBCL patients treated with R-CHOP or R-CHOP-like regimens.This study aimed to investigate the clinical characteristics and treatment outcomes of Chinese DLBCL patients treated with the standard first-line treatment.Methods Clinical data were collected from DLBCL patients who received frontline R-CHOP or R-CHOP-like regimens at the Cancer Hospital Chinese Academy of Medical Sciences&Peking Union Medical College(CHCAMS)between January 1,2005,and December 31,2018.The treatment outcomes were compared with those of patients diagnosed with DLBCL between 2004 and 2017 and who received immunochemotherapy from the United States Surveillance,Epidemiology,and End Results(SEER)database.Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test.Multivariate analysis of progression-free survival(PFS)and overall survival(OS)was performed using Cox proportional hazard regression.Results Overall,1084 patients from the CHCAMS and 4013 patients from the SEER database were included in the study.As of April 30,2022,the median follow-up period for the CHCAMS group was 87.3(range:0.5-195.4)months.For the CHCAMS group,the 5-year PFS and OS rates were 61.7%(95%confidence interval[CI]:58.8-64.7%)and 70.6%(95%CI:67.8-73.4%),respectively.For the SEER group,the 5-year OS rate was 66.5%(95%CI:65.0-68.0%),which was inferior to that of the CHCAMS group(P<0.001).After adjusting for clinical factors and treatment,no significant difference was observed in the OS between the CHCAMS and SEER groups(P=0.867).In the CHCAMS group,multivariate analysis showed that an Eastern Cooperative Oncology Group performance status score≥2,presence of B symptoms,Ann Arbor stage III-IV,elevated serumβ2-microglobulin levels,and bulky mass were independent adverse prognostic factors affecting PFS and OS(P<0.05).Additionally,patients aged over 60 years,elevated lactate dehydrogenase levels,and more than two extranodal sites were independent adverse prognostic factors for OS(P<0.05).Local radiotherapy was significantly associated with better PFS(P<0.001)and OS(P=0.001).Conclusion After adjusting for clinical and treatment-related factors,no significant difference was observed in the 5-year OS rate between Chinese DLBCL patients treated with standard first-line treatment and those from the SEER database.展开更多
Objective:To evaluate whether improved progression-free survival(PFS)from radiotherapy(RT)translates into an overall survival(OS)benefit for diffuse large B-cell lymphoma(DLBCL).Methods:A systematic literature search ...Objective:To evaluate whether improved progression-free survival(PFS)from radiotherapy(RT)translates into an overall survival(OS)benefit for diffuse large B-cell lymphoma(DLBCL).Methods:A systematic literature search identified randomized controlled trials(RCTs)and retrospective studies that compared combined-modality therapy(CMT)with chemotherapy(CT)alone.Weighted regression analyses were used to estimate the correlation between OS and PFS benefits.Cohen’s kappa statistic assessed the consis-tency between DLBCL risk-models and PFS patterns.Furthermore,the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio(HR)according to the PFS patterns.Results:For both 7 RCTs and 52 retrospective studies,correlations were found between PFS HR(HRPFS)and OS HR(HROS)at trial level(r=0.639-0.876),and between PFS and OS rates at treatment-arm level,regardless of CT regimens(r=0.882-0.964).Incorporating RT into CT increased about 18%of PFS,and revealed a different OS benefit profile.Patients were stratified into four CT-generated PFS patterns(>80%,>60-80%,>40-60%,and≤40%),which was consistent with risk-stratified subgroups(kappa>0.6).Absolute gain in OS from RT ranged from≤5%at PFS>80%to about 21%at PFS≤40%,with pooled HROS from 0.70(95%CI,0.51-0.97)to 0.48(95%CI,0.36-0.63)after rituximab-based CT.The OS benefit of RT was predominant in intermediate-and high-risk patients with PFS≤80%.Conclusion:We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.展开更多
基金supported by grants from Sanming Project of Medicine in Shenzhen(No.SZSM202211030)the Science and Technology Department Basic Research Project of Shanxi(No.202203021221284)。
文摘Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.
基金supported by grants from the National Natural Science Foundation(Grant No.81972859 to WT)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2019-I2M-1-003 to WT)the State Key Laboratory of Molecular Oncology Grant(Grant No.SKLMO-2021-03 to WT).
文摘Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.
基金funded by grants from the National Science and Technology Support Program (No. 2014BAI09B12)Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-001)
文摘Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site.Results: In the 1,085 patients, 679(62.6%) cases were nodal DLBCL(N-DLBCL) and 406 cases(37.4%) were extranodal DLBCL(EN-DLBCL). The most common sites of N-DLBCL were lymphonodus(64.8%), Waldeyer's ring(19.7%), mediastinum(12.8%) and spleen(2.7%), while in EN-DLBCL, stomach(22.4%), intestine(16.0%),nose and sinuses(8.9%), testis(8.4%), skin(7.9%), thyroid(6.9%), central nervous system(CNS)(6.4%), breast(5.7%), bone(3.4%), and salivary gland(2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival(OS) rate and progression-free survival(PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9%(P=0.008), and the 5-year PFS were57.0% and 49.0%(P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate(83.6%) and PFS rate(76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach,breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%,respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%.Conclusions: In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.
基金supported by Natural Science Foundation of China (No.81773241)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No.2017I2M-1-006)
文摘Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 cohort that received definitive surgery for early disease.Method：From January 2008 to December 2013,449 consecutive patients with rectal cancer were treated and their outcome maintained in a database.Patients with LARC underwent total mesorectal excision（TME）surgery at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I group pertains to patients whose initially limited disease was not upstaged after TME surgery alone.After propensity score matching（PSM）,comparisons of local regional control（LC）,distant metastasis-free survival（DMFS）,disease-free survival（DFS）and overall survival（OS）were performed using Kaplan-Meier analysis and log-rank test between yp I and p I groups.Down-staging depth score（DDS）,a novel method of evaluating CRT response,was used for subset analysis.Results：Of the 449 patients,168 matched cases were generated for analysis.Five-year LC,DMFS,DFS and OS for stage p I vs.yp I groups were 96.7%vs.96.4%（P=0.796）,92.7%vs.73.6%（P=0.025）,91.2%vs.73.6%（P=0.080）and 93.1%vs.72.3%（P=0.040）,respectively.In the DDS-favorable subset of the yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,respectively）.Conclusions：LC was comparable in both groups;however,distant metastasis developed more frequently in down-staged LARC than de novo early stage cases,reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response.DDS can be an indicator to identify a subset of the yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.
基金supported by grants from the National Natural Science Foundation of China(No.81773241 and No.81871509)。
文摘Objective:The predictive effect of preoperative chemoradiotherapy(CRT)is low and difficult in guiding individualized treatment.We examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative CRT.Methods:From April 2012 to April 2019,95 patients with locally advanced gastric cancer who received preoperative concurrent CRT and who were enrolled in three prospective studies were included.All patients were stage T_(3/4) N_(+).Local control,distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)were evaluated.Clinicopathological factors related to long-term prognosis were analyzed using univariate and multivariate analyses.The down-staging depth score(DDS),which is a novel method of evaluating CRT response,was used to predict long-term outcomes.Results:The median follow-up period for survivors was 30 months.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve predicted by the DDS was 0.728,which was better than the pathological complete response(pCR),histological response and ypN0.Decision curve analysis further affirmed that DDS had the largest net benefit.The DDS cut-off value was 4.pCR and ypN0 were associated with OS(P=0.026 and 0.049).Surgery and DDS are correlated with DMFS,DFS and OS(surgery:P=0.001,<0.001 and<0.001,respectively;and DDS:P=0.009,0.013 and 0.032,respectively).Multivariate analysis showed that DDS was an independent prognostic factor of DFS(P=0.021).Conclusions:DDS is a simple,short-term indicator that was a better surrogate endpoint than pCR,histological response and ypN0 for DFS.
基金This work was supported by the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences,Longevity and Health Project,2021-JKCS-003.
文摘Background: Magnetic resonance(MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation(UHF-WPRT)is a novel approach to radiotherapy for patients with high-risk(HR)and very high-risk(VHR)prostate cancer(PCa).However,the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time.We aimed to estimate the delivered dose,study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods: Ten patients with clinical stage T3a-4N0-1M0-1c PCa,who consecutively received UHF-WPRT,were enrolled prospectively.The contours of the target and organ-at-risks on the position verification-MR(PV-MR),beam-on 3D-MR(Bn-MR),and post-MR(after radiotherapy delivery)were derived from the pre-MR data by deformable image registration.The physician then manually adjusted them,and dose recalculation was performed accordingly.GraphPad Prism 9(GraphPad Prism Software Inc.)was utilized for conducting statistical analyses.Results: In total,we collected 188 MR scans(50 pre-MR,50 PV-MR,44 Bn-MR,and 44 post-MR scans).With median 59 min,the mean prostate clinical target volume(CTV)-V_(100%)was 98.59%±2.74%,and the mean pelvic CTVp-V_(100%)relative percentages of all scans was 99.60%±1.18%.The median V29 Gy change in the rectal wall was−2%(−18%to 20%).With a median follow-up of 9 months,no patient had acute Common Terminology Criteria for Adverse Events(CTCAE)grade 2 or more severe genitourinary(GU)or gastrointestinal(GI)toxicities(0%).Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape(ATS)workflow was technically feasible for patients with HR and VHR PCa,presenting only mild GU and GI toxicities.The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis.Clinical trial registration Chinese Clinical Trial Registry ChiCTR2000033382.
基金This work was supported by the Beijing–Tianjin–Hebei Cooperation Program for Basic Research(Grant No.H2018206591)China National Major Project for New Drug Innovation(Grant No.2017ZX09304015).
文摘Background Rituximab combined with cyclophosphamide,doxorubicin hydrochloride,vincristine,and prednisone(R-CHOP)regimen has improved the survival of diffuse large B-cell lymphoma(DLBCL)patients worldwide,compared with CHOP alone.Several limitations were seen in previous studies of Chinese DLBCL patients treated with R-CHOP or R-CHOP-like regimens.This study aimed to investigate the clinical characteristics and treatment outcomes of Chinese DLBCL patients treated with the standard first-line treatment.Methods Clinical data were collected from DLBCL patients who received frontline R-CHOP or R-CHOP-like regimens at the Cancer Hospital Chinese Academy of Medical Sciences&Peking Union Medical College(CHCAMS)between January 1,2005,and December 31,2018.The treatment outcomes were compared with those of patients diagnosed with DLBCL between 2004 and 2017 and who received immunochemotherapy from the United States Surveillance,Epidemiology,and End Results(SEER)database.Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test.Multivariate analysis of progression-free survival(PFS)and overall survival(OS)was performed using Cox proportional hazard regression.Results Overall,1084 patients from the CHCAMS and 4013 patients from the SEER database were included in the study.As of April 30,2022,the median follow-up period for the CHCAMS group was 87.3(range:0.5-195.4)months.For the CHCAMS group,the 5-year PFS and OS rates were 61.7%(95%confidence interval[CI]:58.8-64.7%)and 70.6%(95%CI:67.8-73.4%),respectively.For the SEER group,the 5-year OS rate was 66.5%(95%CI:65.0-68.0%),which was inferior to that of the CHCAMS group(P<0.001).After adjusting for clinical factors and treatment,no significant difference was observed in the OS between the CHCAMS and SEER groups(P=0.867).In the CHCAMS group,multivariate analysis showed that an Eastern Cooperative Oncology Group performance status score≥2,presence of B symptoms,Ann Arbor stage III-IV,elevated serumβ2-microglobulin levels,and bulky mass were independent adverse prognostic factors affecting PFS and OS(P<0.05).Additionally,patients aged over 60 years,elevated lactate dehydrogenase levels,and more than two extranodal sites were independent adverse prognostic factors for OS(P<0.05).Local radiotherapy was significantly associated with better PFS(P<0.001)and OS(P=0.001).Conclusion After adjusting for clinical and treatment-related factors,no significant difference was observed in the 5-year OS rate between Chinese DLBCL patients treated with standard first-line treatment and those from the SEER database.
基金supported by the National Natural Sci-ence Foundation of China(grant numbers:82002432,82370199)the National Key Research and Development of China(grant number:2020AAA0109504)the Natural Science Foundation of Shandong Province(grant number:ZR2020QH179).
文摘Objective:To evaluate whether improved progression-free survival(PFS)from radiotherapy(RT)translates into an overall survival(OS)benefit for diffuse large B-cell lymphoma(DLBCL).Methods:A systematic literature search identified randomized controlled trials(RCTs)and retrospective studies that compared combined-modality therapy(CMT)with chemotherapy(CT)alone.Weighted regression analyses were used to estimate the correlation between OS and PFS benefits.Cohen’s kappa statistic assessed the consis-tency between DLBCL risk-models and PFS patterns.Furthermore,the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio(HR)according to the PFS patterns.Results:For both 7 RCTs and 52 retrospective studies,correlations were found between PFS HR(HRPFS)and OS HR(HROS)at trial level(r=0.639-0.876),and between PFS and OS rates at treatment-arm level,regardless of CT regimens(r=0.882-0.964).Incorporating RT into CT increased about 18%of PFS,and revealed a different OS benefit profile.Patients were stratified into four CT-generated PFS patterns(>80%,>60-80%,>40-60%,and≤40%),which was consistent with risk-stratified subgroups(kappa>0.6).Absolute gain in OS from RT ranged from≤5%at PFS>80%to about 21%at PFS≤40%,with pooled HROS from 0.70(95%CI,0.51-0.97)to 0.48(95%CI,0.36-0.63)after rituximab-based CT.The OS benefit of RT was predominant in intermediate-and high-risk patients with PFS≤80%.Conclusion:We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.
