食管癌放射治疗临床靶区勾画的相关研究

放疗靶区的界定是影响食管癌精确放射治疗疗效的重要因素.目前食管癌临床靶区(CTV)的勾画范围仍存在较多争议,尚无统一标准.研究提示病理特征、影像学手段及淋巴结转移规律等因素对食管癌CTV勾画可能有指导作用.新的勾画方式如个体化勾画CTV已成为目前的研究热点.     

Assessing respiration-induced tumor motion and internal target volume using four-dimensional computed tomography for radiotherapy of lung cancer

PURPOSE: To assess three-dimensional tumor motion caused by respiration and internal target volume (ITV) for radiotherapy of lung cancer. METHODS AND MATERIALS: Respiration-induced tumor motion was analyzed for 166 tumors from 152 lung cancer patients, 57.2% of whom had Stage III or IV non-small-cell lung cancer. All patients underwent four-dimensional computed tomography (4DCT) during normal breathing before treatment. The expiratory phase of 4DCT images was used as the reference set to delineate gross tumor volume (GTV). Gross tumor volumes on other respiratory phases and resulting ITVs were determined using rigid-body registration of 4DCT images. The association of GTV motion with various clinical and anatomic factors was analyzed statistically. RESULTS: The proportions of tumors that moved >0.5 cm along the superior-inferior (SI), lateral, and anterior-posterior (AP) axes during normal breathing were 39.2%, 1.8%, and 5.4%, respectively. For 95% of the tumors, the magnitude of motion was less than 1.34 cm, 0.40 cm, and 0.59 cm along the SI, lateral, and AP directions. The principal component of tumor motion was in the SI direction, with only 10.8% of tumors moving >1.0 cm. The tumor motion was found to be associated with diaphragm motion, the SI tumor location in the lung, size of the GTV, and disease T stage. CONCLUSIONS: Lung tumor motion is primarily driven by diaphragm motion. The motion of locally advanced lung tumors is unlikely to exceed 1.0 cm during quiet normal breathing except for small lesions located in the lower half of the lung.     

肺癌三维适形放射治疗靶体积确定的影响因素

目的 尽可能合理地确定肺癌三维适形放射治疗的计划靶体积。方法 用透视法观察59例不同解剖部位肺部原发病灶(非小细胞肺癌)随生理活动的移动幅度；用射野片(portal film)测量肺癌放射治疗过程中射野不同方向的移动幅度，计算其随机误差、系统误差和总误差；由5位放射治疗科医生单独在治疗计划CT上勾画大体肿瘤体积(GTV)，比较其中心层面与原计划勾画的吻合性，比较辐射线状测量差异(RLMV)值。结果 以肺下野肿块在头脚方向的移动幅度最大，为14．3mm;肺中野肿块为7．1mm；而左右方向和前后方向的移动范围在4．0mm之内。肺癌放射治疗过程中的移动误差在左右方向为4．2mm，头脚方向为4．6mm；随机误差为3．4mm，系统误差为6．0mm，总误差为6．9mm。与原治疗计划GIV相比，单个放射治疗医生勾画GTV的体积最大相差1．5倍，GTV中心层面与原计划的中心层面无一例完全吻合；RLMV值以向着肺门淋巴结方向的值最大。结论 确定肺癌三维适形放射治疗计划的GTV边界值时应该采取个体化原则，计划靶体积(PTV)应该由一组放射治疗医生共同确定。目前常用的真空体模固定法的误差仍较大，需要进一步改进。     

Evaluation of internal lung motion for respiratory-gated radiotherapy using MRI: Part II-margin reduction of internal target volume

PURPOSE: To analyze the relationship between lung motion and skin surface motion during respiration, determine the uncertainties and variability of such a relationship, and assess the potential of reducing internal target margin for gated radiotherapy. METHODS AND MATERIALS: Three healthy volunteers and four lung cancer patients were recruited in a prospective imaging study using MRI to track the internal lung and external skin motion during breathing. The relationship between the lung and skin motion was modeled using linear regression analysis. The slope of the linear fit and its confidence interval were analyzed for different lung locations, skin surface locations, and breathing patterns from separate imaging sessions. The margins of the internal target volume were calculated based on the residual lung motion during gating and its uncertainties from multiple treatment fractions for the gated treatment. RESULTS: The slope and confidence interval of the linear regression from the motion analysis were uniquely defined by the locations of the lung, skin surface, and breathing patterns. Statistically significant differences were observed among individuals and between different times of measurement. The normal free-breathing motion averaged from all volunteer and patient data was 13.4 +/- 7.4 mm along the superior-inferior (SI) direction and 6.9 +/- 2.6 mm along the anterior-posterior (AP) direction. With simulated respiratory gating, the average margin reduction was 5.5 +/- 4.8 mm and 1.6 +/- 1.0 mm, respectively, along the SI and AP directions (or 36% +/- 15% and 25% +/- 14%, respectively, relative to free-breathing motion). CONCLUSION: Because respiratory movement is rather complex, the relationship between the lung and skin surface motion is affected by many anatomic and physiologic factors. The reduction of internal target margin and efficacy of the free-breathing gating technique should be assessed for individual cases.     

直肠癌放疗个体化CTV勾画的研究进展

CTV的准确勾画是实施直肠癌适形放疗的关键步骤,有多个指南曾对直肠癌放疗涉及的亚解剖区及其解剖边界进行了不同的定义。本文拟对直肠癌放射治疗个体化CTV勾画的最新研究进展进行介绍。     

食管癌放疗靶区勾画的原则及相关问题

食管癌放疗失败的主要原因是肿瘤局部未控或复发,而射线的精确施照与靶区的精确勾画是影响食管癌放疗疗效的两大主要因素.近年来,随着精确放疗技术和放疗设备的快速发展,射线的精确施照技术已有了很大提高,但是食管癌放疗疗效的提高并不显著.因此,靶区精确勾画就显得尤为重要.     

病理特征在食管鳞癌放疗临床靶体积外放边界确定中的价值

目的 研究食管鳞癌镜下浸润转移特点及临床病理特征对其影响,为食管鳞癌临床靶体积(CTV)边界确定提供参考依据.方法 根据每个标本的收缩比计算食管组织体内每厘米长度对应的固定后长度并取材,观察64例标本肿瘤外纵向每厘米范围浸润转移情况.结果 浸润转移阳性率随着距肿瘤边缘距离增加而降低,近端和远端3 cm组出现浸润转移概率分别为4.8%和6.9%,4 cm组分别为3.6%和3.6%.肿瘤长度>5 cm、分化程度低、有淋巴结转移、T3期病例浸润转移发生率高(79.3%:45.7%、77.4%:45.5%、76.0%:51.2%、70.5%:40.0%,χ2=7.52、6.86、3.91、5.36,P=0.006、0.009、0.042、0.021).分化程度、肿瘤长度是影响食管鳞癌浸润转移的主要因素(χ2=0.19、4.82,P=0.020、0.017).结论 食管鳞癌精确放疗若要包括95%的浸润转移病灶CTV应在大体肿瘤体积(GTV)基础上纵向上放3 cm、下放4 cm,若要包括90%的浸润转移病灶则需在GTV基础上上、下均外放3 cm.同时要综合考虑病理特征对靶区范围的影响.

Abstract：

Objective To study the characteristics of microscopic spread of esophageal squamous-cell carcinoma (ESCC) and the influence of clinicopathological features on it to help define the clinical target volume (CTV) margin in radiotherapy.Methods Sixty-four surgical specimens of ESCC were observed for longitudinal microscopic spread per centimeter both proximally and distally from the tumor.The shrinkage ratio of each specimen was calculated and used for tissue incision.Results The further the distance beyond the tumor, the lower the incidence there was of microscopic spread.Positive rates of microscopic spread in group 3 cm of proximal and distal were 4.8% and 6.9%, respectively, and in group 4 cm were both 3.6%.Tumors longer than 5 cm in length,with poorer differentiation, lymph nodes metastasis and more aggressive phase had higher positive rates (79.3% vs 45.7%,77.4% vs 45.5%,76.0% vs 51.2%,70.5% vs 40.0%,χ2=7.52,6.86,3.91,5.36;P=0.006,0.009,0.042,0.021).Differentiation and tumor length were main factors contributing to microscopic spread (χ2=0.19,4.82;P=0.020,0.017).Conclusions To cover 95% of the microscopic spread,a margin of 3.0 cm proximal and 4.0 cm distal beyond gross tumor volume is needed and as to 90%, a margin of 3.0 cm both proximal and distal is needed.Moreover, the influence of pathological features should be taken into account.     

生物靶区与生物适形放疗研究进展

各种影像学方法在肿瘤的诊断和治疗过程中发挥着重要作用。X线、CT、MRI等主要反映解剖形态变化,属解剖学影像范畴,而单光子发射计算机断层显像（single photon emission computed tomography,SPECT）、正电子发射断层显像（positron emission tomography,PET）等可以提供组织和细胞的代谢、增殖、乏氧状态,乃至基因表型的影像,属功能影像或生物学影像范畴,为更全面地了解肿瘤和正常组织的功能状态提供了有力手段。     

FDG-PET/CT imaging for staging and target volume delineation in preoperative conformal radiotherapy of rectal cancer

PURPOSE: To investigate the potential impact of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on staging and target volume delineation for patients affected by rectal cancer and candidates for preoperative conformal radiotherapy. METHODS AND MATERIALS: Twenty-five patients diagnosed with rectal cancer T3-4 N0-1 M0-1 and candidates for preoperative radiotherapy underwent PET/CT simulation after injection of 5.18 MBq/kg of FDG. Clinical stage was reassessed on the basis of FDG-PET/CT findings. The gross tumor volume (GTV) and the clinical target volume (CTV) were delineated first on CT and then on PET/CT images. The PET/CT-GTV and PET/CT-CTV were analyzed and compared with CT-GTV and CT-CTV, respectively. RESULTS: In 4 of 25 cases (24%), PET/CT affected tumor staging or the treatment purpose. In 3 of 25 cases (12%) staged N0 M0, PET/CT showed FDG uptake in regional lymph nodes and in a case also in the liver. In a patient with a single liver metastasis PET/CT detected multiple lesions, changing the treatment intent from curative to palliative. The PET/CT-GTV and PET/CT-CTV were significantly greater than the CT-GTV (p = 0.00013) and CT-CTV (p = 0.00002), respectively. The mean difference between PET/CT-GTV and CT-GTV was 25.4% and between PET/CT-CTV and CT-CTV was 4.1%. CONCLUSIONS: Imaging with PET/CT for preoperative radiotherapy of rectal cancer may lead to a change in staging and target volume delineation. Stage variation was observed in 12% of cases and a change of treatment intent in 4%. The GTV and CTV changed significantly, with a mean increase in size of 25% and 4%, respectively.     

局限期小细胞肺癌胸部放疗靶区的前瞻性随机对照研究

目的 通过开展前瞻性随机对照研究探讨局限期小细胞肺癌(SCLC)胸部不同放疗靶区对预后的影响。方法 选取2002-2017年中山大学肿瘤医院及浙江省肿瘤医院收治的接受2程EP方案诱导化疗后无疾病进展的309例局限期SCLC患者。随机分为照射化疗后残留肿瘤组(159例)和照射化疗前原发病灶组(150例)。2个组患者均采用累及野照射纵隔阳性淋巴结的完整结区。胸部放疗采用45 Gy分30次3周完成,2 次/d,与第3程EP方案化疗同步进行。共化疗4-6程。放化疗后疗效评价完全缓解及部分缓解的患者接受全脑预防性放疗25 Gy分10次2周完成或30 Gy分15次3周完成。采用Kaplan-Meier法分析生存数据。结果 照射化疗后残留肿瘤组和化疗前原发病灶组1、2、5年局部控制率分别为79.4%、61.5%、60.1%和79.8%、66.5%、57.3%(P=0.73)。化疗后残留肿瘤组和化疗前原发病灶组中位生存时间分别为22.1个月(95%CI:18.2~26.0)和26.9个月(95%CI:23.5~30.3),1、3、5、7年总生存率分别为81.1%、31.6%、23.9%、 22.2%和85.3%、36.6%、26.1%、20.0%(P=0.51)。化疗后残留肿瘤组和化疗前原发病灶组2-3级急性放射性食管炎发生率分别为32.9%和43.2%(P=0.01),2-3级肺纤维化发生率分别为2.0%和10.9%(P=0.01)。结论 对于诱导化疗后的局限期SCLC,胸部放疗可仅照射化疗后残留原发灶,纵隔淋巴结引流区可常规采用累及野放疗。     

胸段食管癌术后下颈部淋巴结转移规律及放疗靶区探讨

目的 分析胸段食管癌二野淋巴结清扫术后下颈部淋巴结转移规律,为术后放疗靶区勾画提供参考。方法 搜集本院2004—2009年收治的 126例胸段食管癌术后区域淋巴结转移患者的临床资料,参照Som等颈部影像学分区将下颈部分为Ⅰ区(上纵隔淋巴结)、Ⅱ区(脏器淋巴结)、Ⅲ_a区(颈内静脉内淋巴结)、Ⅲ_b区(颈内静脉外淋巴结)、Ⅳ区(锁骨上淋巴结)、Ⅴ区(颈后三角淋巴结),并分析各区淋巴结转移情况。组间比较采用χ²检验,Logistic回归分析各区间淋巴结转移关系。结果 全组 126例区域淋巴结转移患者下颈部淋巴结转移占68.3%(86例),Ⅰ、Ⅱ、Ⅲ_a区淋巴结转移之和占下颈部淋巴结转移的95%(82例),其中Ⅰ、Ⅱ区占85%(73例)。右颈部淋巴结转移多于左颈部(53.2%∶30.2%,χ²=13.73,P=0.000),右侧Ⅰ、Ⅱ、Ⅲ_a区淋巴结转移比例均高于左侧(43.7%∶15.1%、17.5%∶7.1%、17.5%∶5.6%,χ²=24.79、6.22、8.77,P=0.000、0.013、0.003)。结论 胸段食管癌下颈部淋巴结转移主要集中于喉返神经旁(Ⅰ、Ⅱ区)与颈内静脉内(Ⅲ_a区)淋巴结。     

An assessment of interfractional uterine and cervical motion: Implications for radiotherapy target volume definition in gynaecological cancer

PURPOSE: To assess interfractional movement of the uterus and cervix in patients with gynaecological cancer to aid selection of the internal margin for radiotherapy target volumes. METHODS AND MATERIALS: Thirty-three patients with gynaecological cancer had an MRI scan performed on two consecutive days. The two sets of T2-weighted axial images were co-registered, and the uterus and cervix outlined on each scan. Points were identified on the anterior uterine body (Point U), posterior cervix (Point C) and upper vagina (Point V). The displacement of each point in the antero-posterior (AP), supero-inferior (SI) and lateral directions between the two scans was measured. The changes in point position and uterine body angle were correlated with bladder volume and rectal diameter. RESULTS: The mean difference (+/-1SD) in Point U position was 7mm (+/-9.0) in the AP direction, 7.1mm (+/-6.8) SI and 0.8mm (+/-1.3) laterally. Mean Point C displacement was 4.1mm (+/-4.4) SI, 2.7mm (+/-2.8) AP, 0.3 (+/-0.8) laterally, and Point V was 2.6mm (+/-3.0) AP and 0.3mm (+/-1.0) laterally. There was correlation for uterine SI movement in relation to bladder filling, and for cervical and vaginal AP movement in relation to rectal filling. CONCLUSION: Large movements of the uterus can occur, particularly in the superior-inferior and anterior-posterior directions, but cervical displacement is less marked. Rectal filling may affect cervical position, while bladder filling has more impact on uterine body position, highlighting the need for specific instructions on bladder and rectal filling for treatment. We propose an asymmetrical margin with CTV-PTV expansion of the uterus, cervix and upper vagina of 15mm AP, 15mm SI and 7mm laterally and expansion of the nodal regions and parametria by 7mm in all directions.     

食管癌根治性放疗后局部复发再程三维适形放疗临床分析

目的 研究食管癌根治性放疗后局部复发行再程三维适形放疗(3DCRT)的安全性、疗效及影响生存预后因素.方法 回顾性分析2010年1月至2014年4月本院收治的46例食管癌根治性放疗后局部复发行3DCRT再程治疗患者的治疗效果,并应用Log-rank进行单因素预后分析,用Cox比例风险模型进行预后的多因素分析.结果 6例患者未完成放疗,40例患者顺利完成放疗,3DCRT总有效率为80.0％ (32/40).1、2年生存率分别为47.5％ (19/40)、20.0％ (8/40).再程放疗中出现2+3级的放射性消化道反应19例(47.5％)、放射性肺炎14例(35.0％)、造血系统毒性反应6例(15.0％)、心脏毒性4例(10.0％),全组均未出现4度以上放射性损伤及治疗相关性死亡.单因素分析显示年龄(x2=8.432,P=0.015)、放疗间隔时间(x2=7.006,P=0.008)、放疗剂量(x2=18.718,P=0.000)、大体肿瘤体积(GTV) (x2=10.121,P=0.006)、辅助化疗(x2=5.014,P=0.025)、肿瘤长度(x2=7.391,P=0.025)、野内复发(x2 =9.933,P=0.002)、肿瘤控制情况(x2=14.665,P=0.001)与预后密切相关;病变部位有影响总生存的趋势(x2=5.493,P=0.064);多因素分析显示年龄(x22=4.759,P=0.029)、放疗间隔时间(x2 =4.139,P=0.041)、GTV (x2=4.799,P=0.024)、肿瘤控制情况(x2=4.501,P=0.030)是影响总生存时间的重要因素.结论 对于食管癌根治性放疗后局部复发患者,3DCRT再程放疗虽然毒性反应大,但其可提高近期疗效.年龄、放疗间隔时间、GTV、肿瘤控制情况是再程放疗的预后因素.     

42例放疗后复发食管癌三维适形放疗的疗效分析

目的 探讨三维适形放疗(3DCRT)在食管癌首程放疗后局部复发患者中应用的可行性、疗效和放射损伤及影响因素.方法 42例首程放疗后局部复发的食管癌患者,采用3DCRT技术进行二程放疗.放疗处方剂量中位值54 Gy(50～64 Gy),1.8～2.0 Gy/次,5次/周.结果 随访截至2008年12月31日,随访率为100%,其中随访满1、2年者分别为20、22例.42例患者中完全缓解7例,部分缓解31例,无进展4例.全组患者1、2年总生存率分别为60%和24%.全组≥2级放射性食管炎15例,其中2级13例,3级2例.≥2级放射性肺炎9例,其中2级8例,3级1例.≥2级血液学副反应3例,其中2级2例,3级1例.本组共死亡28例,其中死于局部复发9例、远处转移7例、食管瘘1例、食管狭窄1例、全身衰竭4例、心脏病3例、电解质紊乱1例、死因不明1例.结论 食管癌首程放疗后局部复发采用3DCRT二程放疗是可行的,有较好临床症状缓解率和即时疗效,部分患者可延长生存期;但再程放疗并发症较高,临床应用时应严格掌握其适应证.     

妇科肿瘤伴腹主动脉旁淋巴节转移IMRT靶区勾画探讨

目的 初步探讨妇科肿瘤伴腹主动脉旁淋巴节转移患者IMRT的CTV勾画范围。方法 回顾分析2010—2016年收治的56例妇科肿瘤伴腹主动脉旁淋巴结转移患者。通过影像学方法判断腹主动脉旁转移淋巴结数目和分布情况。结果 56例妇科肿瘤患者腹主动脉旁淋巴结转移共计108个,平均每位患者转移淋巴结数目为2个(1~4个),腹主动脉旁转移淋巴结平均直径为2.3 cm (1.2~4.0 cm)。20个(19%)淋巴结位于L₄水平,38个(35%)转移淋巴结位于L₃水平,44个(41%)转移淋巴结位于L₂水平,6个(5%)位于L₁水平。腹主动脉旁左侧组转移淋巴结共71个(66%)。腹主动脉-腔静脉间组转移淋巴结共20个(19%)。下腔静脉旁右侧组转移淋巴结共17个(15%)。结论 妇科肿瘤腹主动脉旁淋巴结勾画不应以血管周围外扩固定范围方式勾画,腹主动脉旁左侧应充分勾画在靶区范围内,靶区上界应至肾动脉水平,对肾动静脉旁有淋巴结转移者靶区上界应适当扩展。     

脊椎转移癌的三维适形放射治疗

目的分析三维适形放射治疗对脊椎转移癌的应用价值。方法全组22例,其中男14例,女8例。年龄48～75岁。原发癌为非小细胞肺癌8例、乳腺癌6例、前列腺癌和甲状腺癌各3例,2例为肾癌转移。采用三维适形放疗,根据CT显示病变范围设定临床靶区,设5～6个共面照射野,根据剂量分布决定每个照射野的权重。10%脊髓体积剂量不超过15%。中位剂量36Gy/8次(平均35～40Gy/7～10次)。治疗期间配合适量激素。结果止痛效果明显,总有效率达100%。截止2005年2月,有随访结果的18例,其中8例生存1年,4例存活2年,2例存活3年,有4例存活4年健在。结论三维适形照射技术对脊椎转移癌是一种较为理想的治疗方法。     

颈段胸上段食管癌三维适形放射治疗疗效观察

目的　探讨三维适形放射治疗颈段胸上段食管癌的疗效和分析影响预后的因素。方法　回顾性分析 33例颈段胸上段食管癌患者接受三维适形放射治疗 ( 2Gy/次 ,5次 /周 ,总剂量 6 6～6 8Gy ,6～ 7周完成 )的疗效 ,生存分析采用Kaplan Meier法 ,多因素分析采用Cox比例风险模型。结果　 1、2、3年局部控制率分别为 87.9%、75 .8%、4 5 .5 % ;1、2、3年生存率分别为 78.8%、6 6 .8%、4 4 .2 % ,中位生存期 33个月 ;1、2、3年无瘤生存率分布为 72 .7%、6 0 .6 %、30 .3%。急性放射反应主要是急性放射性食管炎和急性放射性气管炎 ,多为 1、2级。多因素分析结果显示原发肿瘤浸润深度、淋巴结转移和病变长度是影响预后的主要因素。结论　三维适形放射治疗是治疗颈段胸上段食管癌的有效治疗方法。原发肿瘤浸润深度、淋巴结转移和病变长度对患者的预后有重要影响。