Induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma

The value of adding induction chemotherapy(IC) to concurrent chemoradiotherapy(CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma(NPC) remains unclear.In our recent article entitled "Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma:a phase 3,multicentre,randomised controlled trial" published in the Lancet Oncology,we reported the results of a phase Ⅲ,multicenter,randomized controlled trial comparing cisplatin,5-fluorouracil,and docetaxel(TPF) IC plus CCRT versus CCRT alone in patients wit hT3-4N1/TxN2-3M0 NPC(Clinical Trials.gov registration number NCT01245959).The IC-plus-CCRT group showed significantly higher 3-year failure-free survival,overall survival,and distant failure-free survival rates than the CCRT-alone group,with an acceptable toxicity profile.Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC.However,long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy,and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.

PhaseⅡstudy of induction chemotherapy followed by concurrent chemoradiotherapy with raltitrexed and cisplatin in locally advanced nasopharyngeal carcinoma

Objective:For locally advanced nasopharyngeal carcinoma(LA-NPC)patients,high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome.Raltitrexed,a specific thymidylate synthase inhibitor with a convenient administration schedule,has an acceptable and manageable toxicity,and possesses radio-sensitizing properties.To investigate the efficacy and safety of raltitrexed and cisplatin induction chemotherapy and concurrent chemoradiotherapy(IC+CCRT)in patients with LA-NPC,a phaseⅡclinical study was conducted.Methods:Sixty eligible patients with LA-NPC were enrolled into this study.A raltitrexed-cisplatin combination was used as part of an IC+CCRT regimen.Raltitrexed-cisplatin IC was given once every 3 weeks(q3 w)for two cycles,followed by raltitrexed-cisplatin based CCRT q3 w for two cycles.Intensity-modulated radiotherapy(IMRT)was given for all enrolled patients.Results:All patients were included in survival analysis according to the intent-to-treat principle.The objective response rate(ORR)3 months after treatment was 98%.The 2-year overall survival(OS)rate was 92%.The median relapse-free survival(RFS)time was 30.5[95%confidence interval(95%CI),28.4-32.3]months.The 2-year RFS rate was 85%.The 2-year local failure-free survival(LFFS)rate was 97%and the 2-year distant metastasis-free survival(DMFS)rate was 88%.Acute toxicities were mostly grade 2 and 3 reactions in bone marrow suppression,gastrointestinal side effect and oropharyngeal mucositis.Only two patients occurred grade 4 acute toxicities,one was bone marrow suppression and the other was dermatitis radiation.Conclusions:The combination of raltitrexed and cisplatin has a comparable efficacy to those in standard firstline therapy.

Predictive value of tumor volume reduction rates before and after induction chemotherapy in determining the radiosensitivity and prognosis of locally advanced nasopharyngeal carcinomas

Objective This study investigated the predictive value of tumor volume reduction rates(TVRRs) before and after induction chemotherapy in determining the radiosensitivity and prognosis of patients with locally advanced nasopharyngeal carcinomas(NPCs). Methods The clinical data of 172 patients with locally advanced primary NPCs who were treated from January 2009 to December 2012 were collected. Tumor regression was evaluated based on the results of the computed tomography scan or magnetic resonance imaging studies. Data about the tumor diameters before and after induction chemotherapy and after radiotherapy as well as the survival times of the patients were obtained. Results All 172 patients had NPCs. After radiotherapy, the TVRR in patients without residual tumor cells was higher than that in patients with residual tumor cells after induction chemotherapy(median values: 47.7% and 15.1%, respectively), and the 5-year survival rates were 80.3% and 45.6%, respectively. Neck lymph node metastasis was observed in 161 of 172 patients, and the TVRRs were similar(median values: 46.8% in 161 patients without residual tumor cells and 11.1% in 161 patients with residual tumor cells). The 5-year survival rate of the 161 patients without residual tumor cells was 84.5%, and that of patients with residual tumor cells was 37.3%. As shown by the receiver operating characteristic(ROC) curve, the area under the curve(AUC) of the ROC curve for TVRRs in patients with primary NPCs but without residual tumors was 0.851, whereas that for TVRRs in patients with neck lymph node metastasis but without residual tumors was 0.784. This result indicates that TVRR has a high diagnostic performance. The univariate Cox regression analysis showed that clinical stage, TVRR in primary NPCs, neck lymph node metastatic lesions before and after induction chemotherapy, presence or absence of residual tumor cells in primary NPCs, and neck lymph node metastatic lesions after radiotherapy were significantly correlated to overall survival(OS). Results of the multivariate Cox regression analysis showed that clinical stage and presence or absence of residual tumor cells in the lymph nodes after radiotherapy were the independent prognostic factors of OS.Conclusion The TVRR after induction chemotherapy may be an effective predictive indicator of the treatment efficacy of radiotherapy in patients with NPC.

CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

Combined chemo-radiotherapy in locally advanced nasopharyngeal carcinomas

AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy(CCRT)(22/40 patients)or CCRT alone(18/40)from March 2006 to March 2012.Patients underwent fiberoscopy with biopsy of the primitive tumor,and computed tomography scan of head,neck,chest and abdomen with and without contrast.Cisplatin was used both as induction and as concomitant chemotherapy,while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions(total dose,70 Gy).The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly.This retrospective analysis was approved by the review boards of the participating institutions.Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS:Thirty-three patients were males and 7 were females.Median follow-up time was 58 mo(range,1-92 mo).In the sub-group of twenty patients with a follow-up time longer than 36 mo,the 3-year survival and disease free survival rates were 85%and 75%,respectively.Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%.Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients.Grade 2 mucositis was seen in 29 patients,while grade 2 xerostomia was seen in 30 patients.Overall toxicity was manageable and it did not cause any significant treatment delay.In the whole sample population,long term toxicity included grade 2 xerostomia in 22 patients,grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION:Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC.The role of adjuvant chemotherapy remains to be defined.

鼻咽癌放化疗治疗患者外周血PD-1及免疫指标水平的变化及其临床意义

目的探讨鼻咽癌放化疗治疗患者外周血程序性死亡受体1(PD-1)及免疫指标水平的变化及其临床意义。方法回顾性选取2020年1月至2023年江苏省肿瘤医院收治的90例鼻咽癌患者,所有患者均经病理确诊并接受放化疗治疗,采集其血液样本之后采用流式细胞术对不同时间段(治疗前、新辅助化疗后、放疗后)外周血淋巴细胞亚群比例、外周血PD-1、CD8^(+)CD28^(+)细胞比例的水平变化予以动态监测并比较。结果鼻咽癌患者新辅助化疗后CD3^(+)、CD4^(+)细胞比例、CD4^(+)/CD8^(+)比值分别为(72.28±8.37)%、(39.27±8.58)%、1.58±0.67,均明显高于治疗前,CD3-CD16^(+)CD56^(+)、CD19^(+)细胞比例分别为(18.27±8.38)%、(7.87±4.08)%,均明显低于治疗前,差异均有统计学意义(P<0.05);新辅助化疗后与治疗前的CD8^(+)细胞比例比较,差异无统计学意义(P>0.05)。鼻咽癌患者新辅助化疗之后CD8^(+)CD28^(+)细胞比例为(10.68±3.87)%,明显高于治疗前,差异有统计学意义(P<0.05);新辅助化疗后与治疗前的外周血PD-1水平比较,差异无统计学意义(P>0.05)。放疗后与治疗前的CD3^(+)细胞比例比较,差异无统计学意义(P>0.05);鼻咽癌患者放疗后CD4^(+)细胞比例、CD4^(+)/CD8^(+)比值、CD19^(+)细胞比例分别为(26.68±6.09)%、0.88±0.29、(3.69±2.36)%,均明显低于治疗前,CD8^(+)、CD3-CD16^(+)CD56^(+)细胞比例分别为(31.03±8.08)%、(27.39±10.26)%,均明显高于治疗前,差异均有统计学意义(P<0.05)。鼻咽癌患者放疗后CD8^(+)CD28^(+)细胞比例为(7.08±2.57)%,明显低于治疗前,外周血PD-1水平为(13.38±6.27)%,明显高于治疗前,差异均有统计学意义(P<0.05)。结论新辅助化疗之后鼻咽癌患者外周血T细胞亚群比值处于持续上调趋势,而放疗完成后处于下降趋势,表明鼻咽癌患者于放疗完成后免疫功能受损;放疗完成后鼻咽癌患者T细胞PD-1表达水平明显上调,提示PD-1抑制剂最佳使用时间可能为放化疗完成时,抗PD-1维持治疗可发挥持久、高效的抗肿瘤作用。

Effect of induction chemotherapy with cisplatin, fluorouracil, with or without taxane on locoregionally advanced nasopharyngeal carcinoma: a retrospective, propensity score-matched analysis

Background:Available data in the literature comparing different induction chemotherapy(IC)regimens on locoregionally advanced nasopharyngeal carcinoma(NPC)are scarce.The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane,cisplatin and 5-fluorouracil(TPF)or cisplatin and 5-fluorouracil(PF)as IC followed by concurrent chemoradiotherapy(CCRT).Methods:In total,1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study.We compared overall survival(OS),disease-specific survival(DSS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival,using the pro-pensity score method.Results:In total,1256 patients received TPF or PF as IC backbone.The TPF group showed significantly better OS(hazard ratio[HR],0.660;95%confidence interval[CI]0.442-0.986;P=0.042),DSS(HR,0.624;95%CI 0.411-0.947;P=0.027)and DMFS(HR,0.589;95%CI 0.406-0.855;P=0.005)compared with the PF group in multivariable analy-ses.Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS(88.1%vs.80.7%;P=0.042),DSS(88.5%vs.80.7%;P=0.021)and DMFS(87.9%vs.78.6%;P=0.012)rates compared with the PF group.There were no significant differences in locoregional relapse-free survival before or after matching.Conclusions:In our study,IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen.However,a prospective randomized clinical trial to validate these findings is necessary.

Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxanebased induction chemotherapy and concurrent chemo-radiotherapy in the modern era

Objective:To evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension(ICE)treated with induction chemotherapy(ICT)followed by chemo-intensity-modulated radiotherapy(CTRT)at a tertiary cancer center.Methods:We retrospectively analyzed 45 patients with histologically proven,non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016.Patients were classified as minor ICE or major ICE,based on the extent of ICE.All the patients received 2-3 cycles of a taxane-based ICT regimen followed by CTRT.Radiotherapy was delivered with"riskadapted"intensity-modulated radiotherapy(IMRT)technique in all patients.Results:After a median follow up of 45 months(range:8-113 months),the estimated 5-year DFS,LRFS,DMFS,and OS of the entire cohort was 58%,82%,67%and 74%respectively.On multivariate analysis,histological subtype was an independent predictor of LRFS,and age was an independent predictor of DFS.The extent of ICE showed only a trend towards worse DFS(P=0.06).None of the factors significantly predicted for DMFS or OS.Gender,N-stage,and response to ICT did not significantly affect any of the outcomes.Grade 2 or worse subcutaneous fibrosis was seen in 22%of patients and grade 2 or worse xerostomia was seen in 24%of patients at last follow up.Thirty-three percent of the patients developed clinical hypothyroidism at last follow up.None of the patients experienced any neurological or vascular complications.Conclusions:Taxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension.Distant metastasis continues to be the predominant problem in these patients.

尼妥珠单抗联合TP方案诱导化疗对EGFR阳性局部晚期鼻咽癌的近期疗效及其安全性

目的探讨尼妥珠单抗(NTZ)联合TP方案诱导化疗对表皮生长因子受体(EGFR)阳性局部晚期鼻咽癌的近期疗效及其安全性。方法前瞻性选取贵州省人民医院2020年1月-2022年12月收治的Ⅲ-ⅣA期鼻咽癌患者48例,采用随机数表法分为NTZ+多西他赛/白蛋白紫杉醇+顺铂(NTP)组(n=24)与多西他赛/白蛋白紫杉醇+顺铂(TP)组(n=24)。NTP组2或3个周期诱导治疗后序贯NTZ配合顺铂同步放化疗,采用免疫组化检测肿瘤组织EGFR表达水平,探究NTP组患者EGFR表达强度和尼妥珠单抗的治疗效果;比较两组诱导治疗结束后的近期疗效、肿瘤退缩率及不良反应发生情况。结果NTP组EGFR阳性表达率为100%,EGFR表达强度与联合NTZ的诱导治疗疗效相关(P<0.05);诱导治疗结束后的两组疗效比较,NTP组颈部淋巴结的客观缓解率(ORR)明显高于TP组(75.0%vs.45.8%,P=0.039),两组肿瘤原发病灶及总体(肿瘤原发病灶和颈部淋巴结)ORR比较差异无统计学意义(P>0.05);不良反应方面,NTP组白细胞减少、胃肠道反应发生率低于TP组(P<0.05),皮疹发生率高于TP组(P<0.05),两组肝功能异常、血红蛋白及血小板减少比较差异无统计学意义(P>0.05)。结论鼻咽癌组织中存在不同强度的EGFR表达,EGFR表达强度较高时,联合NTZ诱导治疗临床获益更明显;NTZ联合TP诱导方案治疗对于局部晚期鼻咽癌颈部淋巴结的近期疗效和安全性较好。

经口微创手术治疗诱导化疗后下咽癌疗效分析

目的对局部晚期下咽癌经诱导化疗降期后行微创及开放手术患者预后及喉功能保留情况分析。方法回顾性分析2016年1月~2021年12月北京同仁医院接受诱导化疗并疗效评估为大部分缓解(partial response,PR),即肿瘤靶病灶最大径之和减少≥70%后,行保留喉功能手术的54例下咽癌患者临床资料,对接受经口微创手术和颈外入路开放手术的患者术后喉功能恢复情况、生存率等进行对比分析。结果54例患者中接受经口微创手术28例,接受颈外入路部分下咽和(或)部分喉切除手术26例,两组患者术后3年生存率分别为63%和59%,差异无统计学意义(χ^(2)=0.288,P>0.05),微创手术组术后呼吸功能(χ^(2)=14.676,P<0.05)、吞咽功能(χ^(2)=10.956,P<0.05)及发声功能(χ^(2)=13.290,P<0.05)的恢复优于开放手术组,差异均有统计学意义。结论经口微创治疗在诱导化疗后降期的下咽癌患者治疗中能够获得与开放手术近似的生存率,且经口微创手术后喉功能恢复更好。

基于MRI影像组学模型预测鼻咽癌诱导化疗疗效的研究

目的:探讨基于MRI的影像组学模型预测鼻咽癌诱导化疗疗效的价值。方法:回顾性分析经病理证实的184例(132例作为训练集,52例作为验证集)接受诱导化疗的鼻咽癌患者治疗前2周内、诱导化疗结束后T_(2)WI和CE-T_(1)WI两个序列图像。根据实体肿瘤疗效评价标准,将患者分为反应组(102例)和无反应组(82例)。分别勾画治疗前两个序列图像中肿瘤的瘤体作为感兴趣区进行影像组学特征提取。分析影像组学特征、临床病理特征及治疗前的血液学指标,构建了3个模型,用于预测鼻咽癌诱导化疗疗效,分别为模型1(CE-T_(1)WI+T_(2)WI影像组学)、模型2(临床病理特征+治疗前血液学指标)、模型3(模型1+模型2)。绘制受试者操作特征(ROC)曲线并评估模型的预测效能。利用决策分析曲线评价不同风险阈值下模型的净获益情况。结果:模型3其训练集的ROC曲线下面积(AUC)值、敏感度、特异度、阳性预测值、阴性预测值分别为0.951、0.831、0.869、0.881、0.815,验证集对应的值分别为0.948、0.774、0.952、0.960、0.741。在训练集及验证集中,模型1的性能均优于模型2(0.940 vs.0.745,0.952 vs.0.608,P值均<0.001),同时模型3的预测性能均高于模型2(0.951 vs.0.745,0.948 vs.0.608,P值均<0.001)。决策曲线示三个模型在评价鼻咽癌诱导化疗疗效时均有明确临床获益,并且模型3、模型1均优于模型2。结论:与使用治疗前临床病理特征+血液学指标模型相比,影像组学模型以及影像组学+临床病理+血液学指标模型均能更好地预测鼻咽癌诱导化疗的疗效,对鼻咽癌化疗方案的制定具有一定的指导价值。

ASL-MRI对局部晚期鼻咽癌诱导化疗反应及近期疗效的早期预测价值

目的:通过动脉自旋标记磁共振成像(ASL-MRI)监测局部晚期鼻咽癌(LA-NPC)诱导化疗前、后的肿瘤血流量(TBF),探讨ASL-MRI早期预测LA-NPC诱导化疗反应及近期疗效的价值。方法:收集38例初诊LA-NPC患者,于诱导化疗前、后行ASL-MRI,以获得诱导化疗前TBF(Pre-TBF)和诱导化疗后TBF(Post-TBF),并计算诱导化疗前、后的TBF变化值(ΔTBF)及变化率(ΔTBF%)。在诱导化疗后,将完全缓解(CR)和部分缓解(PR)归为反应组,疾病稳定(SD)及疾病进展(PD)归为非反应组。在放疗后3个月评估近期疗效,分为CR组和非CR组(PR、SD及PD)。采用单因素及多因素二分类logistic回归分析TBF参数对诱导化疗效果及近期疗效的影响。采用受试者工作特性(ROC)曲线确定诊断效能。结果:38例患者中诱导化疗反应组23例(60.5%),非反应组15例(39.5%)。放疗后3个月CR组22例(57.9%),非CR组16例(42.1%)。诱导化疗反应组在放疗后3个月的CR率显著高于非反应组(73.9%vs.33.3%,P=0.02)。38例患者Pre-TBF显著高于Post-TBF(Z=4.227,P<0.001)。诱导化疗反应组Pre-TBF、ΔTBF及ΔTBF%显著高于非反应组(均P<0.05);放疗后3个月CR组的Pre-TBF、ΔTBF及ΔTBF%显著高于非CR组(均P<0.05)。多因素二分类logistic回归结果显示,Pre-TBF是诱导化疗效果的独立影响因素(P=0.027),ROC曲线下面积为0.745(P=0.012);T分期及ΔTBF%是近期疗效的独立影响因素(均P<0.05),ΔTBF%的ROC曲线下面积为0.807(P=0.001)。结论:治疗前LA-NPC肿瘤血流高灌注提示更好的疗效,Pre-TBF可以预测LA-NPC诱导化疗效果,ΔTBF%可以预测LA-NPC近期疗效。

诱导化疗对鼻咽癌患者免疫功能及炎症指标的影响

目的 探讨诱导化疗(IC)对Ⅲ—Ⅳ期鼻咽癌(NPC)患者免疫功能及炎症指标的影响。方法 选取102例经病理证实的Ⅲ—Ⅳ期NPC患者,接受TPF方案(多西他赛、顺铂及5-氟尿嘧啶,72例)或GP方案(吉西他滨及顺铂,30例);评估患者的近期临床疗效;比较不同临床特征患者IC治疗前免疫功能;比较IC前后外周血T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、B淋巴细胞亚群(CD19^(+))、NK细胞百分比,炎症指标白细胞介素(IL)-6、肿瘤坏死因子α(TNF-α)、中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)、淋巴细胞/单核细胞比值(LMR)和全身免疫炎症指数(SII),以及营养指标总蛋白(TP)、白蛋白(ALB)和前白蛋白(PA)变化;比较不同IC方案和IC周期数患者免疫功能、炎症指标、营养状况。结果102例患者均完成IC,其中0例达完全缓解(CR),87例(85.3%)达部分缓解(PR),13例(12.7%)达到稳定(SD),2例(2.0%)出现进展(PD);客观缓解率(ORR)为85.3%,疾病控制率(DCR)为98.0%。IC后NPC患者CD19^(+)淋巴细胞和NK细胞占比较IC前下降,CD3^(+)、CD4^(+)和CD8^(+)淋巴细胞占比上升,NLR、SII、TP、ALB和PA水平均降低(P<0.05)。与TPF组比较,GP组CD4^(+)/CD8^(+)比值升高,LMR降低(P<0.05);≤3周期组与>3周期组IC前后的免疫功能、炎症指标及营养状况无统计学意义。结论 IC治疗NPC患者近期疗效可,疾病控制率高,能提高NPC患者的细胞免疫功能,降低体液免疫功能,且炎症指标和营养状况均下降。

常规磁共振成像影像特征在鼻咽癌预后预测中的研究进展

鼻咽癌(nasopharyngeal carcinoma,NPC)是一种起源于鼻咽黏膜柱状上皮的恶性肿瘤。目前,临床上主要根据磁共振成像(magnetic resonance imaging,MRI)上原发肿瘤的侵犯程度以及颈部淋巴结大小和位置来确定患者治疗方案,但仍有约10%~30%患者在治疗后发生疾病进展。目前,多功能MRI技术展现出了比常规MRI技术更好的预后预测性能,但由于常规MRI检查具有分辨率高,稳定性好以及普及性广的特点,其在临床应用中的价值不可忽视。且近年来,多项研究细致探究了NPC颅底结构侵犯情况(如颅底骨质侵犯,软组织浸润等)以及转移淋巴结的其他形态学特征(如包膜外侵,淋巴结坏死等)在NPC预后预测中的价值,且将某些常规MRI特征加入目前第八版分期能够显著提高预测性能。因此,本研究就常规MRI[如T2WI、对比增强T1WI(contrast-enhanced T1WI,CE-T1WI)、弥散加权成像(diffusion weighted imaging,DWI)]的多维度原发灶和淋巴结特征在NPC预后预测中的价值进行综述,以为临床诊疗提供可靠的依据。

基于MRI影像组学特征因素预测II~IVa期鼻咽癌患者复发转移风险及辅助化疗受益的临床意义

目的旨在建立一个MRI影像组学和临床因素模型,以预测原发性鼻咽癌(NPC)患者复发转移的风险,并验证其对辅助化疗(adjuvant chemotherapy,AC)疗效的预测作用。方法回顾性分析2018年2月~2021年10月在深圳市龙岗区耳鼻咽喉医院诊断为II~IVa期NPC患者135例。在我院接受标准同步放化疗后,部分患者接受诱导化疗和/或基于顺铂/奈达铂的辅助化疗。利用PyRadiomics平台提取增强MRI序列的成像特征。使用最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)算法过滤与复发或转移相关的特征,在训练队列中通过Cox多变量分析构建临床影像组学模型(clinical radiomics models,CRM),并在验证队列中进行验证。根据模型的Rad评分中位数,将所有患者分为高风险组和低风险组。Kaplan-Meier生存曲线用于比较高风险组和低风险组辅助化疗患者的3年无复发转移生存期(recurrence and metastasis free survival,RMFS)。结果共提取960个成像特征。CRM由9个特征(6个影像学特征和3个临床因素)构成。在训练队列中,3年RMFS的CRM曲线下面积(AUC)为0.867(P<0.001),敏感性和特异性分别为90.32%和79.66%;在验证队列中,AUC为0.836(P<0.001),敏感性和特异性分别为100.0%和71.43%。高风险组和低风险组3年RMFS分别为42.86%(27/63)和94.44%(68/72)(Log rank=50.818,P<0.001)。在CRM高风险患者中,接受辅助化疗的患者3年RMFS明显优于未接受患者(Log rank=6.204,P=0.013)。结论基于3个临床因素和6个MRI影像学特征的CRM为预测NPC的预后结局提供一种无创的方法,可能有助于指导临床辅助化疗的治疗决策,但还需要进一步外部验证。

Induction gemcitabine and cisplatin in locoregionally advanced nasopharyngeal carcinoma

The standard of care for patients with locoregionally advanced nasopharyngeal carcinoma is concurrent platinum-based chemoradiotherapy.Existing literature have demonstrated that the addition of gemcitabine and cisplatin as induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma may have promising efficacy but were from phase 2 clinical trials.Stronger evidence-based data in forms of phase 3 clinical trial investigating the survival benefits of adding gemcitabine and cisplatin induction chemotherapy for such patients have been urgently warranted.In one of our recent studies published in the New England Journal of Medicine,“Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma”,480 locoregionally advanced nasopharyngeal carcinoma patients from 12 hospitals across China were randomly assigned in a 1:1 ratio to receive either chemoradiotherapy alone or gemcitabine plus cisplatin and chemoradiotherapy.Our findings evinced that,as compared to chemora-diotherapy alone,the addition of induction chemotherapy comprising of gemcitabine plus cisplatin to concurrent cisplatin-radiotherapy to patients with locoregionally advanced nasopharyngeal carcinoma was safe,demonstrated improved recurrence-free survival,overall survival,and distant recurrence-free survival,and marginally superior locore-gional recurrence-free survival.

基于IMRT同步放化疗方案治疗局部晚期鼻咽癌不良预后危险因素及预测模型构建

目的探讨基于调强放疗(IMRT)同步放化疗方案治疗局部晚期鼻咽癌不良预后危险因素并构建预测模型,为临床诊疗方案优化及预后改善提供更多参考。方法收集2012年1月~2017年12月梅州市人民医院接受基于IMRT同步放化疗方案治疗局部晚期鼻咽癌患者190例,分析临床特征资料和随访生存情况,采用单因素和多因素评价患者不良预后独立危险因素;基于独立危险因素构建列线图模型并评价模型预后预测效能。结果190例患者随访过程中死亡26例,累积1年、3年及5年总生存率分别为97.4%、90.7%、87.0%。单因素分析结果显示,年龄、淋巴细胞与单核细胞绝对值比值、乳酸脱氢酶、颅底侵犯、N分级及辅助化疗情况均与局部晚期鼻咽癌不良预后有关,差异有统计学意义(P<0.05)。多因素分析结果显示,乳酸脱氢酶水平≥185 IU/L、颅底侵犯及N3均是局部晚期鼻咽癌不良预后独立危险因素(P<0.05)。将多因素分析有统计学意义指标纳入局部晚期鼻咽癌患者总生存时间列线图模型,患者总生存时间列线图模型用于累积1年、3年及5年总生存时间C-index为0.84(95%CI:0.72~0.86),总生存时间预测AUC分别为0.87(95%CI:0.75~0.93)、0.90(95%CI:0.79~0.96)、0.85(95%CI:0.80~0.98)。结论接受基于IMRT同步放化疗方案治疗局部晚期鼻咽癌患者不良预后可能与乳酸脱氢酶水平、有无颅底侵犯及N分级等密切相关,而根据上述预后因素构建线列图模型在预测患者随访总生存时间方面具有良好效能。

局部晚期头颈鳞状细胞癌诱导免疫治疗联合化疗探索研究

目的 探讨局部晚期头颈鳞状细胞癌(head and neck squamous carcinoma,HNSCC)应用程序性细胞死亡蛋白-1(programmed death-1,PD-1)抑制剂诱导免疫治疗联合化疗的近期疗效及安全性。方法 选择2020年5月-2022年5月济宁医学院附属医院肿瘤科初诊不可手术切除的局部晚期HNSCC患者25例,所有患者接受PD-1抑制剂诱导免疫治疗联合化疗3个周期,具体用法:PD-1抑制剂200 mg,每3周为1个周期,化疗方案为铂类联合紫杉类化疗药物(不适合铂类或紫杉类患者调整为氟尿嘧啶、吉西他滨)。3个周期诱导化疗后采用实体瘤疗效评价标准(RECIST1.1)评估近期疗效,根据PD-L1表达分层分析每亚组疗效分析,另外对治疗相关不良反应进行分析。结果 25例患者中疗效评价部分缓解(PR)21例(84%),其中肿瘤体积缩小≥50%为15例(60%),客观缓解率(ORR)为84%,疾病控制率(DCR)为88%。16例患者进行了联合阳性分数(combined positive score,CPS)检测评估PD-L1表达情况,CPS≥5占50.0%(8/16),其中CPS≥20占25.0%(4/16),另外9例患者未能行CPS检测而PD-L1表达不明。根据PD-L1表达分层分析来看,5≤CPS<20和CPS≥20的患者,肿瘤体积缩小均≥50%,ORR为100%,而CPS<5的所有患者中1例PR肿瘤体积缩小≥50%,PD为2例,ORR为62.5%(5/8)。最常见的不良反应为恶心、白细胞减少和贫血。3例患者出现甲功异常,1例肾功能损害,2例肝功能损害,2例肺炎患者。无3-4级不良反应。结论 局部晚期HNSCC,尤其IVA/IVB期患者,诱导免疫治疗(PD-1抑制剂)联合化疗近期疗效明显,对于CPS≥5的患者疗效更显著,无严重毒副反应发生,有望成为局部晚期头颈部鳞癌新的治疗模式。

Predictive function of tumor burden-incorporated machine-learning algorithms for overall survival and their value in guiding management decisions in patients with locally advanced nasopharyngeal carcinoma

Objective:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain challenging.This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival(OS)and their value in guiding treatment in patients with LA-NPC.Methods:Individuals with LA-NPC were reviewed retrospectively.Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods,the interpretable eXtreme Gradi-ent Boosting(XGBoost)risk prediction model,and DeepHit time-to-event neural network.The models’prediction performances were compared using the concordance index(C-index)and the area under the curve(AUC).The patients were divided into two cohorts based on the risk predictions of the most successful model.The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone.Results:The 1221 eligible individuals,assigned to the training(n=813)or validation(n=408)set,showed significant respective differences in the C-indices of the XGBoost,DeepHit,and nomogram models(0.849 and 0.768,0.811 and 0.767,0.730 and 0.705).The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS(0.881 and 0.760,0.845 and 0.776,and 0.764 and 0.729,P<0.001).IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group.Conclusion:This research used machine-learning algorithms to create and verify a comprehensive model inte-grating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC.This model could be valuable for delivering patient counseling and conducting clinical evaluations.

基于CT影像组学结合临床影像特征预测局部晚期鼻咽癌诱导化疗疗效

目的:探讨基于增强CT的影像组学结合临床影像特征的列线图在预测局部晚期鼻咽癌(LA-NPC)患者诱导化疗(ICT)疗效中的价值。方法:回顾性分析2014年7月至2022年3月178例LA-NPC(Ⅲ、Ⅳ期)患者的临床及CT图像资料,以7:3随机将患者分为训练组(n=125)和测试组(n=53)。采用3D-Slicer勾画容积感兴趣区(VOI)并用Pyradiomics包提取特征。使用单-多因素Logistic回归选择临床预测因子。采用最小绝对收缩与选择算法(LASSO)筛选组学特征,最后通过多变量Logistic回归构建临床、影像组学及联合模型,并绘制列线图。以受试者工作特征曲线(ROC)的曲线下面积(AUC)评估和比较三种模型的预测效能。应用决策曲线(DCA)观察列线图的临床净获益。结果:Logistic回归分析结果显示T分期(OR=0.45,P=0.004)、癌灶强化程度(OR=2.706,P=0.038)、血小板/淋巴细胞比值(PLR)(OR=0.289,P=0.024)是ICT疗效的临床预测因子,基于以上3者构建临床模型。基于22个与ICT疗效显著相关的组学特征构建影像组学模型。ROC曲线分析结果显示,联合模型的预测效能最佳;训练组中,联合模型、临床模型、影像组学模型的AUC分别为0.821、 0.732、0.798;验证组中,三者的AUC分别为0.836、0.793、0.779。DCA分析进一步表明,列线图模型对比单纯组学模型,其人群净获益率更高。结论:基于增强CT的影像组学联合传统临床影像特征的列线图能直观、量化、个性化地预测LA-NPC患者ICT的疗效,优于单一模型,可以作为一种无创的预测工具。