Is dose escalation achievable for esophageal carcinoma?

Aim

To investigate the feasibility of dose escalation using rapid arc (RA) and Helical Tomotherapy (HT) for patients with upper, middle and distal esophageal carcinomas, even for large tumor volumes.

Background

In esophageal cancer, for patients with exclusive radio-chemotherapy, local disease control remains poor. Planning study with dose escalation was done for two sophisticated modulated radiotherapy techniques: Rapid arc against Tomotherapy.

Materials and methods

Six patients treated with a RA simultaneous integrated boost (SIB) of 60 Gy were re-planned for RA and HT techniques with a SIB dose escalated to 70 Gy. Dose volume histogram statistics, conformity indices and homogeneity indices were analyzed. For a given set of normal tissue constraints, the capability of each treatment modality to increase the GTV dose to 70 Gy was investigated.

Results

Either HT or VMAT may be used to escalate the dose delivered in esophageal tumors while maintaining the spinal cord, lung and heart doses within tolerance. Adequate target coverage was achieved by both techniques. Typically, HT achieved better lung sparing and PTV coverage than did RA.

Conclusions

Dose escalation for esophageal cancer becomes clinically feasible with the use of RA and HT. This promising result could be explored in a carefully controlled clinical study which considered normal tissue complications and tumor control as endpoints.     

食管癌术后并发症及其处理

食管癌是我国一种常见的消化道恶性肿瘤,居世界癌症死因第7位,中国癌症死因第4位。其中以中段鳞状细胞癌多见,临床表现以晚期进行性吞咽困难为主,确诊主要以胃镜病理活检为金标准,其治疗方法主要有手术、放疗、化疗及分子靶向治疗等。但目前治疗上仍然以手术为主,术前术后放化疗为辅。然而,随着手术在食管癌治疗中适应症的不断扩大、根治性手术淋巴结的扩大清扫及拥有基础疾病高龄患者的增多,术后并发症的发生率不可避免的随之增加。本文将重点阐述吻合口瘘、吻合口狭窄、呼吸及心血管并发症、乳糜胸、胃排空障碍、膈疝、喉返神经损伤及单纯脓胸、严重腹泻、呕血等食管癌术后常见、严重并发症的病因、临床表现与诊断、治疗及其预防。通过对食管癌术后并发症的充分认识及有效预防,从而对食管癌手术成功率及患者术后生存质量的提高、肿瘤预后的改善起到了重要作用。     

术后放化疗对淋巴结阳性食管鳞癌患者的临床意义

目的:探讨术后放化疗在治疗淋巴结阳性食管鳞癌中的毒副作用、临床预后及可能影响因素。方法:选择淋巴结阳性食管鳞癌患者为研究对象,纳入研究患者共计64例,术后放疗剂量为50 Gy,化疗方案为顺铂联合紫杉醇(21 d方案),观察并记录患者不良反应情况,分析患者3年无瘤生存情况,并进一步探讨可能影响预后的相关因素。结果:患者出现骨髓抑制(白细胞下降),其中Ⅰ/Ⅱ度骨髓抑制39例(61.0%),Ⅲ/Ⅳ度骨髓抑制19例(29.7%);胃肠道反应Ⅰ/Ⅱ度15例(23.4%),Ⅲ/Ⅳ度6例(9.4%);无肝肾功能异常或明显过敏反应;Ⅰ/Ⅱ度放射性食管炎和放射性气管炎分别为18例(28.1%)和14例(21.9%),晚期肺损伤Ⅲ/Ⅳ度2例(3.1%)。64例患者的3年无瘤生存期为28.8个月,无瘤生存率为46.9%。本研究未发现明显影响术后放化疗治疗淋巴结阳性食管鳞癌患者预后的相关因素(P0.05)。结论:淋巴结阳性食管鳞癌患者术后放化疗的不良反应主要为白细胞下降、胃肠道反应和放射性损伤等,患者均可耐受,且3年无瘤生存显著改善,可用于淋巴结阳性食管鳞癌患者治疗。     

MACC1蛋白在食管癌中的表达及其临床意义

目的：探讨结肠癌转移相关基因1（metastasis—associated in colon cancer-1,MACCl）在食管癌组织中的表达及其临床意义。方法：采用免疫组化EnVinsion法检测MACCl蛋白在88例食管癌组织中的表达,统计学分析MACCl蛋白在不同病理分级、TNM分期中表达的差异性。结果：免疫组化结果显示MACCl蛋白的阳性表达主要位于胞浆中。MACCl蛋白在食管癌组织中的总阳性率为88．64％;在I、II、Ⅲ级食管癌组织中的阳性率分别为14．29％、93．65％、100％,经Kruskal．WallisH检验差异性非常显著（P=0．0000）;在I、IIa、IIb、Ⅲ期食管癌中的阳性率分别是16．67％、89．47％、100％、100％,经Kruskal．WallisH检验差异性非常显著（P=0．0000）。结论：MACCl蛋白在食管癌中呈过度表达,其表达与病理分级、TNM分期相关,提示MACCl可能在食管癌的发生、发展中起重要作用。MACCl蛋白可能成为检测食管癌的发病及判断预后的生物学指标之一。     

β-tubulinIII在食管癌中的表达及在个体化化疗方案中的作用

目的：探讨β—tubulinIII在食管癌组织中的表达,分析其与食管癌生物学行为的关系,及根据其表达结果制定个体化化疗方案的疗效。方法：应用免疫组化（SP）法检测β-tubulinIII在55例食管癌组织中的阳性表达,采用X^2检验方法分析其阳性表达与肿瘤临床病理学特征之间的关系。依据低表达（阴性）对紫杉类抗微管药物相对敏感,选用紫杉醇联合顺铂方案;高表达（阳性）相对不敏感的原则,选择吉西他滨联合顺铂方案。对照组选用紫杉醇联合顺铂化疗方案。比较两组客观缓解率（ORR）及疾病控制率（DCR）的差异,及无进展生存时间（PFS）和中位生存期（MST）的差异。结果：B—tubulinIII在55例食管癌组织中阳性表达为16例（29．09％）,在肿瘤组织中的表达与食管癌的浸润深度、淋巴结转移及肿瘤分期相关（P〈0．05）,而与年龄、性别、组织学分化程度无关（P〉0．05）。实验组ORR为54．55％（30／55）优于对照组32．50％（13／40）,x^2=-4．543,P=0．033;DCR为69．09％（38／55）优于对照组47．50％（19／40）,xZ=-4．498,P=0．034。差异有统计学意义。实验组与对照组的PFS分别为5．2月和4．5月（x^2=4．215,P=0．040）,MST分别为8．9月和7．4月（x^2=6．146,P=0．013）,差异有统计学意义。结论：食管癌细胞存在β-mbulin III的表达,且与肿瘤细胞的浸润深度、淋巴结转移及临床分期相关。检肿瘤标本中13-tubulinⅢ表达,有助于为实施个体化化疗提供一种选择药物的方法。     

不同剂量西洛他唑强化抗血小板对冠脉支架术后血小板高反应性的影响

目的：观察临床应用不同方案强化抗血小板治疗改善冠脉支架术后血小板高反应性的可行性、安全性及有效性。方法：选择2009年3月至2011年2月在沈阳军区总医院、中国医科大学第一附属医院、解放军第463医共入选560例冠脉支架术后血小板高反应性（HPR Highon-treatment Platelet Reactivity）患者,在给予阿司匹林300mg／天,氯吡格雷150mg／天,3天后HPR仍未缓解者,随机分为两组,一组在强化抗血小板治疗即阿司匹林300mg,氯吡格雷150mg的基础上加用小剂量西洛他唑（50mg,2／日）,另一组在标准两联方案即阿司匹林300mg,氯吡格雷75mg的基础上加用西洛他唑100mg,2／日,3天后测定HPR的缓解情况。结果：大剂量氯吡格雷治疗3天后HRP的缓解卒为54-3％（304／560）,接受不同西洛他唑剂量治疗3天后又有58．6％的患者HPR缓解,但是西洛他唑50mg组和100mg组HRP缓解率无差别（59．4％VS57．8％,P=0．80）。两组患者30天随访均无死亡及卒中事件,无主要及次要出血事件。结论：强化抗血小板治疗可改善冠脉支架术后的血小板高反应性且未增加出血风险,但其临床获益还需更长时间的随访结果进一步明确,两种强化抗血小板治疗方案对改善冠脉支架术后HPR的作用相似。     

CYFRA21-1 and CEA are useful markers for predicting the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma

Background: Chemoradiotherapy (CRT) is currently performed for patients with advanced esophageal carcinoma. Sensitivity of tumours to CRT differs from one case to another and may be influenced by the expression of biological molecules. The aim of this study was to identify biological markers which could predict sensitivities of esophageal squamous cell carcinoma (ESCC) to CRT.

Methods: A total of 84 patients with stage I–IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) levels were measured before CRT by enzyme-linked immunosorbent assays in patients with primary ESCCs using 3.4?ng ml^?1 and 3.3?ng ml^?1, respectively, as cut-off values. The relationships between pretreatment expression of CYFRA 21-1 and CEA and the effectiveness of CRT were analysed.

Results: The complete response (CR) rates of the primary tumours estimated by computed tomography in patients with high levels of CYFRA21-1 and CEA were 10% (3/30) and 4.2% (1/24), while in cases with low CYFRA21-1 and CEA the CR rates were 50% (27/54) and 48.3% (29/60), respectively (p?=?0.002 and 0.003). The effective rates (CR+PR) in CYFRA21-1 high and low groups were 60% (18/30) and 96.3% (52/54), while in CEA high and low groups they were 58.3% (14/24) and 93.3% (56/60), respectively (p?=?0.013 and 0.013).

Conclusion: CYFRA21-1 and CEA may be helpful in predicting the responsiveness in ESCC of primary lesions to CRT, although the results should be confirmed in larger, more homogeneous studies.     

Evaluating tissue levels of the eight trace elements and heavy metals among esophagus and gastric cancer patients: A comparison between cancerous and non-cancerous tissues

BackgroundConsidering the affecting role of environmental factors including trace elements and heavy metals on the upper gastrointestinal (GI) cancers, there is paucity of empirical research in tissue evaluations.ObjectivesThe present study aimed to measure the tissue content of some trace elements and heavy metals such as zinc (Zn), chromium (Cr), manganese (Mn), tin (Sn), copper (Cu), aluminum (Al), lead (Pb), and iron (Fe) in esophagus and gastric cancerous tissues compared to the adjacent healthy tissues.MethodsIn a cross-sectional study, the aforementioned trace elements and heavy metals were evaluated among patients with esophagus and gastric cancers. During endoscopy, multiple samples were taken from cancerous lesions and the adjacent healthy tissues. The classic flame atomic absorption spectroscopy (FAAS) method was employed as the study framework.ResultsFifty patients with the mean age of 53.92 ± 8.73 were enrolled in the current study. Thirteen patients suffered from esophageal cancer and thirty-seven patients were afflicted with gastric cancer. The results revealed significant differences in the median concentrations of Zn, Cr, Sn and, Cu (P < 0.05) between the two groups. Although there were no significant changes in the tissue content in the esophageal samples, in the median concentrations of Zn, Cr and, Sn (P < 0.05) in gastric tissues, significant differences were observed. Further, the results indicated that gender enacted an affecting role in the level of some trace elements and heavy metals.ConclusionThe tissue contents of some elements were altered in gastric and esophageal cancers; this difference may reflect the underlying mechanism of cellular changing during the tumorigenesis or direct exposure of these elements. It seems that under the shade of other coexisting risk factors, larger cohort studies are suggested to be conducted to investigate other probable aspects in this area of interest.     

Deep learning dose prediction for IMRT of esophageal cancer: The effect of data quality and quantity on model performance

PurposeTo investigate the effect of data quality and quantity on the performance of deep learning (DL) models, for dose prediction of intensity-modulated radiotherapy (IMRT) of esophageal cancer.Material and methodsTwo databases were used: a variable database (VarDB) with 56 clinical cases extracted retrospectively, including user-dependent variability in delineation and planning, different machines and beam configurations; and a homogenized database (HomDB), created to reduce this variability by re-contouring and re-planning all patients with a fixed class-solution protocol.Experiment 1 analysed the user-dependent variability, using 26 patients planned with the same machine and beam setup (E26-VarDB versus E26-HomDB). Experiment 2 increased the training set by groups of 10 patients (E16, E26, E36, E46, and E56) for both databases.Model evaluation metrics were the mean absolute error (MAE) for selected dose-volume metrics and the global MAE for all body voxels.ResultsFor Experiment 1, E26-HomDB reduced the MAE for the considered dose-volume metrics compared to E26-VarDB (e.g. reduction of 0.2 Gy for D95-PTV, 1.2 Gy for Dmean-heart or 3.3% for V5-lungs). For Experiment 2, increasing the database size slightly improved performance for HomDB models (e.g. decrease in global MAE of 0.13 Gy for E56-HomDB versus E26-HomDB), but increased the error for the VarDB models (e.g. increase in global MAE of 0.20 Gy for E56-VarDB versus E26-VarDB).ConclusionA small database may suffice to obtain good DL prediction performance, provided that homogenous training data is used. Data variability reduces the performance of DL models, which is further pronounced when increasing the training set.     

三维适形调强放疗联合榄香烯注射液对食管癌患者血清肿瘤标志物和T淋巴细胞亚群的影响

摘要 目的：探讨三维适形调强放疗联合榄香烯注射液对食管癌患者血清肿瘤标志物和T淋巴细胞亚群的影响。方法：选取我院于2016年8月到2019年12月期间接诊的食管癌患者60例,根据随机数字表法分为对照组（n=30）和研究组（n=30）,对照组患者予以三维适形调强放疗,研究组在对照组基础上联合榄香烯注射液治疗,比较两组患者疗效、生存质量、血清肿瘤标志物、T淋巴细胞亚群以及不良反应。结果：研究组患者治疗6周后的临床总有效率为63.33%（19/30）,高于对照组患者的36.67%（11/30）（P<0.05）。两组治疗6周后血清癌胚抗原（CEA）、糖类抗原199（CA199）水平均较治疗前降低,且研究组低于对照组（P<0.05）。两组患者治疗6周后CD3⁺、CD4⁺、CD4⁺/CD8⁺水平均下降,但研究组高于对照组（P<0.05）,CD8⁺水平均升高,但研究组低于对照组（P<0.05）。两组治疗6周后卡劳夫斯基（KPS）评分均较治疗前升高,且研究组高于对照组（P<0.05）。两组不良反应发生率对比未见统计学差异（P>0.05）。结论：三维适形调强放疗联合榄香烯注射液治疗食管癌患者,疗效较好,可有效阻止疾病进展,改善患者生存质量和降低血清肿瘤标志物水平,减轻机体免疫抑制,且不增加不良反应发生率。