Postoperative chemoradiotherapy with capecitabine and oxaliplatin vs.capecitabine for pathological stage N2 rectal cancer

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.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy

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.

同步推量调强放疗在局部晚期非小细胞肺癌中的应用

背景与目的局部晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的标准治疗方案为放疗联合化疗,但其生存仍不令人满意。随着调强放疗技术的发展,同步推量(simultaneous integrated boost,SIB)技术成为局部晚期NSCLC的研究方向。本研究拟探讨局部晚期NSCLC采用SIB调强放疗技术的有效性和安全性。方法回顾性分析北京大学肿瘤医院2015年6月-2018年12月采用SIB技术进行放疗的局部晚期NSCLC患者资料,采用Kaplan-Meier方法进行统计分析,分析其疗效、生存及治疗相关毒性。结果研究纳入93例患者,中位随访时间34.23个月,3年生存率、无进展生存率、无局部区域复发生存率和无远处转移生存率分别为53.0%、37.0%、50.5%和50.5%。3级放射性食管炎发生率为5.4%,≥3级放射性肺炎发生率为2.2%。结论局部晚期NSCLC采用SIB调强放疗技术安全有效。

Adjuvant radiotherapy in central hepatocellular carcinoma after narrow-margin hepatectomy:A 10-year real-world evidence

Objective:A prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma(HCC)after narrow-margin hepatectomy(<1 cm).This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy.Methods:Patients with central HCC after narrow-margin hepatectomy(<1 cm)were prospectively assigned to adjuvant radiotherapy group and control group.Patients'outcome,adverse events,long-term recurrence and survival rates were investigated.Results:The 1-,5-,and 10-year recurrence-free survival(RFS)rates were 81.0%,43.9%,and 38.7%,respectively in adjuvant radiotherapy group and 71.7%,35.8%,and 24.2%,respectively in control group(log-rank test,P=0.09).The 1-,5-,and 10-year overall survival(OS)rates were 96.6%,54.7%,and 42.8%,respectively in adjuvant radiotherapy group and 90.2%,55.1%,and 30.0%,respectively in control group(log-rank test,P=0.20).The 1-,5-,and 10-year RFS rates for patients with small HCC(≤5 cm)were 91.1%,51.6%,and 48.4%,respectively in adjuvant radiotherapy group and 80.0%,36.6%,and 26.6%,respectively in control group(log-rank test,P=0.03).Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group(log-rank test,P=0.05).Conclusions:Our updated results showed a sustained clinical benefit on reducing recurrence,improving longterm survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy.Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains challenging.Few studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after treatment.This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital.Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant predictors.Results:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had ypCR.Univariate and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive consistency.The follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 months.The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT.Endoscopic mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

Addition of rituximab is not associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma

Background： The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma （DLBCL） remains to be defined. We aimed to compare CHOP plus rituximab （R-CHOP） with CHOP alone and determine the value of radiotherapy in these patients. Methods： Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study. Results： Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response （CR） rate was 77% both in R-CHOP and CHOP groups （P=0.945）. After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival （PFS） （76% vs. 85%; log-rank P=0.215） and 5-year overall survival （OS） （90% vs. 96%; log-rank P=0.175） compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone （86% vs. 71%; log-rank P=0.005）. At multivariate analysis, patients who had CR （P=0.008） and received radiotherapy （P=0.003） were significantly associated with superior PFS. Conclusions： CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients.

Management of extramedullary plasmacytoma: Role of radiotherapy and prognostic factor analysis in 55 patients

Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods： Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51（range, 22–77） years. The median tumor size was 3.5（range, 1.0–15.0） cm. The median applied dose was 50.0（range, 30.0–70.0） Gy. Thirty-nine patients（70.9%） presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery（S） alone, 3 received chemotherapy（CT） alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients.Results：The median follow-up duration was 56 months.The 5-year local recurrence-free survival（LRFS）,multiple myeloma-free survival（MMFS）,progression-free survival（PFS）and overall survival（OS）rates were 79.8%,78.6%,65.2% and 76.0%,respectively.Univariate analysis revealed that RT was a favourable factor for all examined endpoints.Furthermore,head and neck EMPs were associated with superior LRFS,MMFS and PFS.Tumor size〈4 cm was associated with superior MMFS,PFS and OS;serum M protein negativity was associated with superior MMFS and PFS;age≥50 years and local recurrence were associated with poor MMFS.The dose≥45 Gy group exhibited superior 5-year LRFS,MMFS and PFS rates（94.7%,94.4%,90.0%,respectively）,while the corresponding values for the dose〈45 Gy group were 62.5%（P=0.008）,53.3%（P=0.036）and 41.7%（P〈0.001）.Conclusions：Involved-site RT of at least 45 Gy should be considered for EMP.Furthermore,patients with head and neck EMP,tumor size〈4 cm,age〈50 years and serum M protein negativity had better outcomes.

放射治疗对初诊转移性头颈鳞癌预后的影响

目的基于美国SEER数据库的资料,评估放疗对初诊转移性头颈鳞癌(HNSCC)患者预后的影响。方法利用SEER数据库筛选2010—2015年初诊为转移性HNSCC的患者1226例,包括放疗组762例(62.1%),未放疗组464例(37.9%)。采用Kaplan-Meier法计算癌症特异性生存(CSS)和总生存(OS),在全组患者中通过Cox多因素回归和倾向配比评分(PSM)评估放疗对预后的影响。依据多因素分析结果将患者分为低、中和高风险组,并在不同风险组中分析放疗对生存的影响。结果全组患者中位CSS和OS时间分别为11.0个月和10.0个月;放疗组和未放疗组的中位CSS时间分别为13.0个月和6.0个月,中位OS时间分别为12.0个月和6.0个月。多因素分析显示年龄、原发灶部位、T分期、N分期、转移脏器个数、手术、放疗和化疗是独立的预后影响因素(CSS:P值为0.045、0.021、0.001、0.002、<0.001、<0.001、<0.001、<0.001;OS:P值为0.002、<0.001、0.002、<0.001、<0.001、<0.001、<0.001、<0.001)。PSM配对后,在低、中、高风险组中,放疗和未放疗患者3年CSS分别为:62.5%∶23.5%、22.4%∶15.7%和10.5%∶9.6%(P=0.008、0.001、0.203);3年OS分别为:58.0%∶20.8%、19.8%∶12.7%和7.0%∶6.1%(P=0.002、0.001、0.166)。结论放疗显著提高低风险和中风险组患者的CSS和OS,但高风险组患者不能从放疗中生存获益。

A retrospective study of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia during definitive concurrent chemoradiotherapy in patients with esophageal squamous carcinoma

Objective:To compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)for preventive or delayed treatment in neutropenia,completion rate of concurrent chemoradiotherapy and hospitalization rate in patients with esophageal squamous carcinoma during definitive concurrent chemoradiotherapy.Methods:A total of 70 patients with esophageal squamous carcinoma in Peking University Cancer Hospital from January 2019 to December 2020,who received PEG-rhG-CSF during concurrent chemoradiotherapy,were enrolled in this retrospective analysis.There were 32 patients in the preventive group,and 38 patients in the delayed group.The incidence of neutropenia,completion rate of concurrent chemoradiotherapy and neutropeniarelated hospitalization rate were compared between PEG-rhG-CSF preventive group and delayed group.Results:The incidence of severe neutropenia(Grades 3–4)in all patients was 31.4%.Comparison between preventive group and delayed group showed that the incidence of severe neutropenia was 6.3%and 39.4%(χ^(2)=10.428,P=0.001),respectively.In preventive group,the incidence of severe neutropenia was 3.7%and 20.0%,respectively,for primary prevention and secondary prevention of PEG-rhG-CSF(χ^(2)=12.321,P=0.001).The completion rate of concurrent chemoradiotherapy was 93.8%in the preventive group and 63.2%in the delayed group(χ^(2)=9.220,P=0.002).The incidence of treatment interruption was 25.7%in the whole group,12.5%in the preventive group and 36.8%in the delayed group(χ^(2)=5.389,P=0.020).Seven patients(7/70,10.0%)were hospitalized and treated with intravenous antibiotics for neutropenia,including 1 in the preventive group and 6 in the delayed group(P=0.078).Conclusions:Prophylactic use of PEG-rhG-CSF during concurrent chemoradiotherapy for patients with esophageal squamous carcinoma can effectively reduce the incidence of neutropenia,ensure the safety of treatment,and improve the completion rate of concurrent chemoradiotherapy.

Long-term follow-up of volumetric modulated arc therapy in definitive radiotherapy for cervical cancer: A single-center retrospective experience

Objective:To evaluate the treatment outcomes and toxicity of volumetric modulated arc therapy(VMAT)in definitive radiotherapy for patients with cervical cancer.Methods:Medical records of 440 patients with cervical cancer treated with VMAT in definitive radiotherapy with or without concurrent chemotherapy between January 2010 and June 2015 in our institution were retrospectively reviewed.A dose of 45 Gy was prescribed to the planning target volume with VMAT in 25 fractions,followed by high-dose rate intracavitary brachytherapy with 28–36 Gy in 4–6 fractions.Survival time was estimated using Kaplan-Meier method.Risk factors for treatment failure were identified using Cox proportional hazards regression model.Results:The median follow-up periods were 58.3 months(range:2.7–112.9 months).The 3-and 5-year survival rates were overall survival(OS)79.4%and 74.4%,cancer-specific survival(CSS)81.4%and 77.1%,progressionfree survival(PFS)73.3%and 71.1%,locoregional control(LC)83.3%and 82%and distant metastasis-free survival(DMFS)80.8%and 77.7%,respectively.The 5-year OS for patients with different stages was IB191.6%,IB2100%,IIA 82.5%,IIB 74.4%,IIIA 57.1%,IIIB 61.7%and IVB 17.6%,respectively.Of the 124 patients with recurrence,93 patients(75.0%)experienced distant failure.Multivariate analysis showed that non-squamous cell carcinoma of the cervix(P<0.001),more advanced stage(P=0.004),pelvic lymph node metastasis(P<0.001)and para-aortic lymph node metastasis(P=0.019)were all independent risk factors of PFS.The incidence of grades 3–4 late bowel toxicities was 2.7%.No grades 3–4 bladder toxicity was observed.Conclusion:This study demonstrated that the use of VMAT in definitive radiotherapy resulted in satisfactory outcomes with acceptable toxicities for patients with cervical cancer.Distant metastasis predominated as the pattern of disease relapse.Further studies are needed to investigate the intensified systemic therapies.