头颈部癌调强放疗过程中腮腺及靶区体积变化的临床分析

目的 研究头颈部癌患者在放疗过程中腮腺体积及GTV变化。方法 5例头颈部鳞癌（4例口咽鳞癌和1例喉鳞癌）患者均接受全程调强放疗。从第一次放疗开始至结束，1次／周三维锥形束CT（CBCT）检查。每次的CBCT图像与疗前CT图像进行融合，在每层图像上勾画出腮腺外轮廓，同时将GTV内放疗中出现的气腔勾画出来。经统计后分析放疗中腮腺体积、GTV内气腔大小的变化。结果 放疗结束时腮腺体积为疗初的90．1％，52．3％，即腮腺体积缩小了9．9％～47．7％；GTV内气腔由疗前的0体积逐渐增加，疗终时气腔体积占GTV的3．7％。16．8％。结论 放疗过程中腮腺体积及GTV内气腔体积存在着明显变化，利用CBCr可分析这种变化，为二次调强计划的实施奠定基础。     

锥形束CT研究头颈部肿瘤调强放疗摆位误差

[目的]应用IGRT机载千伏级锥形束CT(CBCT)研究头颈部肿瘤调强放疗体位的线性误差和旋转误差。[方法]应用医科达Synergy IGRT系统治疗头颈部肿瘤12例,共治疗217次。CBCT分别在治疗前、治疗中(摆位误差纠正后)、治疗后共扫描3次,得到3组X线容积图像(XVI),将3组XVI图像和计划CT图像的靶中心匹配,获得3组X、Y、Z三维方向的线性误差和旋转误差。[结果]12例每次治疗开始前的CBCT共217次,线性误差在X、Y、Z方向上系统误差(均数)±随机误差(标准差)分别为(-0.04±2.63)mm、(0.07±1.69)mm、(-1.15±1.33)mm,旋转误差为(0.10°±1.14°)、(0.16°±1.41°)、(-0.06°±1.22°)。纠正后的X、Y、Z3个方向线性误差及旋转误差的系统误差和随机误差均低于纠正前水平。治疗中(摆位误差纠正后)与治疗后的误差结果无显著性差异。[结论]CBCT实时纠正头颈部肿瘤放疗的摆位误差可缩小摆位误差并减少计划肿瘤靶区(PTV)外扩。头颈部肿瘤患者分次治疗中的摆位误差小。     

图像引导的放射治疗在头颈部肿瘤

随着图像引导的放射治疗(image-guided radiotherapy,IGRT)技术的出现,肿瘤放射治疗进入一个精确化、个体化和自适应性的时代.目前该技术在多种肿瘤治疗中得以应用.本文就其在头颈部肿瘤治疗中的作用、特殊性和具体应用作一综述,以期待其能更好地为开展头颈部肿瘤的IGRT临床研究提供帮助.     

头颈部肿瘤ART体积和剂量比较:系统评价与Meta分析

目的 对头颈部肿瘤放疗ART靶区与OAR体积和剂量变化系统评价与Meta分析,说明ART在治疗中作用。方法 文献检索纳入相关研究,分析指标原发肿瘤(GTV-T、GTV-N)与腮腺体积;靶区D₉₅ D_mean,同、异侧腮腺(I-PG、C-PG)D_mean,脊髓、脑干D_max。结果 17个研究336病例纳入Meta分析。原发肿瘤与腮腺体积变化明显,GTV-T、GTV-N、I-PG第15-20天及第20天后体积显著减小(P<0.05),C-PG第20天后显著减小(P=0.004)。实际剂量分析,原发肿瘤D_95、D_mean无变化,脊髓D_max第20-25天增加2.26 Gy (P=0.000),脑干D_max第20天前无显著变化(P=0.090),第25天后增加1.78 Gy (P=0.020),I-PG D_mean第20-25天增加2 Gy (P=0.000),C-PG D_mean第20天前增加,第25天后无显著变化(P=0.110)。ART剂量分析,脊髓、脑干D_max均下降(MD=-2.15,95% CI为-3.12~-1.18,P=0.000;MD=-2.20,95% CI为-3.32~-1.09,P=0.000),I-PG D_mean下降约3.5 Gy,敏感性分析显示C-PG D_mean结果不稳定。结论 原发肿瘤、腮腺体积显著变化,脊髓、脑干D_max,腮腺D_mean实际剂量显著增加,GTV-T、GTV-N剂量变化不明显,ART能很好保护OAR剂量要求,对同步放化疗局部晚期头颈部肿瘤患者第15-20天及第25天左右实施ART计划可能获得较好剂量增益。     

头颈部肿瘤摆位误差对调强放疗计划的影响

目的研究头颈部肿瘤患者调强放疗分次间摆位误差对患者所接受的放射剂量的影响。方法在患者治疗前利用机载千伏级锥形束CT(KV-CBCT)进行扫描,在XVI软件里自动将CBCT图像和计划CT图像进行配准得到平移和旋转误差。在Pinnacle治疗计划系统中把平移和旋转误差模拟出来,然后重新计算剂量,将得到新的剂量分布和原计划进行比较、分析。评价指标包括原发肿瘤计划靶区(GTV-T-P)的平均剂量(Dm)、包含95%体积的剂量(D95);脑干1%体积的剂量(D1%)及1cc的剂量;脊髓1%体积的剂量(D1%)及1cc的剂量;双侧腮腺的平均剂量及接受超过30Gy剂量的体积(V30)。应用SPSS16.0软件进行统计分析。结果头颈部肿瘤分次间沿X、Y、Z轴的平移误差和旋转误差分别为(1.02±0.83)、(1.28±1.08)、(1.27±1.06)mm和(0.79±0.67)°、(1.00±0.82)°、(0.73±0.68)°。患者脑干、脊髓、腮腺受量变化差异有统计学意义,原发肿瘤计划靶区平均受量差异无统计学意义,其D95统计结果有明显差异,但其平均变化率仅为2.18%。结论调强放疗中摆位误差无论对靶区还是正常组织的剂量分布都产生影响,而正常组织的剂量和靶区相比受摆位误差的影响更大。     

头颈部肿瘤摆位误差对调强放疗计划的影响

目的研究头颈部肿瘤患者调强放疗分次间摆位误差对患者所接受的放射剂量的影响。方法在患者治疗前利用机载千伏级锥形束CT（KV—CBCT）进行扫描,在XVI软件里自动将CBCT图像和计划cT图像进行配准得到平移和旋转误差。在Pinnacle治疗计划系统中把平移和旋转误差模拟出来,然后重新计算剂量,将得到新的剂量分布和原计划进行比较、分析。评价指标包括原发肿瘤计划靶区（GTV—T．P）的平均剂量（Dm）、包含95％体积的剂量（D95）;脑干1％体积的剂量（D1％）及1cc的剂量;脊髓1％体积的剂量（D1％）及1cc的剂量;双侧腮腺的平均剂量及接受超过30Gy剂量的体积（V30）。应用SPSS16．0软件进行统计分析。结果头颈部肿瘤分次间沿X、Y、Z轴的平移误差和旋转误差分别为（1．02±0．83）、（1．28±1．08）、（1．27±1．06）mm和（0．79±0．67）°、（1．00±O．82）°、（0．73±0．68）°。患者脑干、脊髓、腮腺受量变化差异有统计学意义,原发肿瘤计划靶区平均受量差异无统计学意义,其D95统计结果有明显差异,但其平均变化率仅为2．18％。结论调强放疗中摆位误差无论对靶区还是正常组织的剂量分布都产生影响,而正常组织的剂量和靶区相比受摆位误差的影响更大。     

鼻咽癌适形调强放疗相关体积变化对靶区剂量影响分析

目的：在图像引导的调强放射治疗（intensity modulated radiotherapy,IMRT）局部晚期鼻咽癌的过程中,评价外轮廓、腮腺及体质量的变化对靶区剂量影响的临床价值。方法：收集2011-06—01—2012—03—31贵州省肿瘤医院收治完成全程治疗的局部晚期鼻咽癌患者,可评价15例,放疗采用图像引导的调强放射治疗技术,于放疗第1周每天及以后每周三维锥形束CT（conebeamCT,CBCT）检查,通过图像观察腮腺及外轮廓位移。分别在放疗至33．6Gy／15次及62．72Gy／28次时重新定位扫描,通过骨配准把最新扫描的CT图像导入放疗前的图像中,可以明显观察GTVnx、腮腺及外轮廓的变化,并根据变化进行改野后,重新计算后续放疗的剂量。观察改野后腮腺及GTVnx所接受剂量的变化。结果：靶区体积、鼻咽部外轮廓体积随放疗变化差异无统计学意义,P值分别为0．817和0．280;放疗至15及28次时,左右腮腺体积与放疗前相比较差异均有统计学意义,P〈O．05;以28次缩小最为显著。随着放疗的进行,腮腺的外侧缘比内侧缘缩小明显,腮腺受照射的平均剂量增加,并且外轮廓横径均发生内移,外轮廓缩小的差异有统计学意义,P=0．007;重新勾画靶区后,GTVnx所接受的剂量较原始计划差异无统计学意义,P=0．051;放疗期间的外轮廓和腮腺的位置、体积及患者体质量的变化,对靶区所受到的剂量影响差异无统计学意义,P〉0．05。结论：在放疗过程中,可能需考虑由于外轮廓、腮腺及体质量的变化而修改靶区。     

调强放疗时代头颈部肿瘤腮腺组织损伤的认识及研究进展

腮腺的放射性损伤是头颈部肿瘤放疗最常见的并发症之一。调强适形放射治疗较常规放疗对腮腺有更好的保护作用,但腮腺的放射性损伤不可避免。在调强时代如何动态评估放射治疗中腮腺的变化及以更优化的方案防护腮腺功能值得探讨。本文就近年来调强放射治疗对头颈部肿瘤患者腮腺影响的相关研究及进展作一综述。     

肺肿瘤在线与离线结合锥形束CT图像引导放疗的可行性研究

目的 探讨肺肿瘤在、离线结合锥形束CT(CBCT)图像引导放疗的可行性.方法 14例行三维适形放疗的肺肿瘤患者入组.放疗前后分别行在线CBCT扫描1次,并与计划CT图像配准,记录各个方向的配准差值.放疗前后配准获得的平移矢量分别作为分次间误差和分次内误差,利用CTV外放公式分别计算未行在线校正以及在线校正后的cTV外放.分别以0.5、1.5 mm为允许的最大残余系统摆位误差,计算预测总系统摆位误差所需的最少CBCT图像数以及离线校正系统摆位误差后的CTV外放.结果 未行在线校正时,左右、头脚、前后方向上群体化CTV外放分别为5.7、8.0、7.8 mm;每分次放疗均行在线校正时,3个方向上群体化CTV外放分别为2.4、2.4、2.3 mm.分别以0.5 mm或1.5 mm为允许的最大残余系统误差,计算预测系统摆位误差所需的最少CBCT图像数为9套或7套,对系统摆位误差进行离线校正后,左右、头脚和前后方向上群体化CTV外放分别为3.3 mm或3.9 mm、3.7 mm或4.3 mm和3.6 mm或4.3 mm.结论 基于CBCT图像分析的在线校正和离线校正均能明显减小摆位误差,并有助于缩小CTV外放.肺肿瘤患者进行在线、离线相结合的图像引导放疗是可行的.     

ExacTrac X线系统二种不同图像配准序列在头颈部肿瘤放疗中的应用研究

目的 比较2种不同ExacTrac X线系统(ExacTrac X-ray,ET)图像配准序列与锥形束CT(cone beam CT,CBCT)图像配准序列在头颈部肿瘤放疗中的应用,探讨ET在头颈部肿瘤放疗中的临床最优配准序列.方法 选择行调强放射治疗(intensity-modulated radiation the...     

The function of the parotid gland following radiation therapy for head and neck cancer

The parotid gland was selected for study of its salivary output before and after radiation therapy for head and neck cancer. Before radiation therapy, a sialogram of the parotid gland was performed with the patient's head positioned for radiation therapy; a lateral radiographic view of the parotid gland was used to compare with the radiation treatment portal to determine the portion of the parotid gland to he irradiated. Samples of stimulated saliva were collected from the parotid gland before and at 1 and 6 months post-radiation. Eighteen patients with head and neck cancer who received radiation therapy were studied. The data showed that in the irradiation of nasopharyageal, advanced oropbaryngeal and Waldeyer's ring lesions, 100% of the parotid gland was irradiated; for the early oropharyageal and hypopbaryugeal lesions, from 30 to 90% of the parotid gland was irradiated and for the supragiottic and oral cavity lesions, 25–30% of the parotid gland was irradiated. When 100% of the parotid gland was irradiated, no saliva was produced at 1 month post-radiation; this remained the same when re-tested at 4–8 months, however, when any portion of the parotid gland was not irradiated, there was residual salivary function.     

Importance of the initial volume of parotid glands in xerostomia for patients with head and neck cancers treated with IMRT

OBJECTIVE: Our aim was to evaluate predictors of xerostomia in patients with head and neck cancers treated with intensity-modulated radiation therapy (IMRT). METHODS: Thirty-three patients with pharyngeal cancer were evaluated for xerostomia after having been treated with IMRT. All patients were treated with whole-neck irradiation of 46-50 Gy by IMRT, followed by boost IMRT to the high-risk clinical target volume to a total dose of 56-70 Gy in 28-35 fractions (median, 68 Gy). For boost IMRT, a second computed tomography (CT-2) scan was done in the third to fourth week of IMRT. Xerostomia was scored 3-4 months after the start of IMRT. RESULTS: The mean doses to the contralateral and ipsilateral parotid glands were 24.0 +/- 6.2 and 30.3 +/- 6.6 Gy, respectively. Among the 33 patients, xerostomia of grades 0, 1, 2 and 3 was noted in one, 18, 12 and two patients, respectively. Although the mean dose to the parotid glands was not correlated with the grade of xerostomia, the initial volume of the parotid glands was correlated with the grade of xerostomia (P = 0.04). Of 17 patients with small parotid glands (< or =38.8 ml) on initial CT (CT-1), 11 (65%) showed grade 2 or grade 3 xerostomia, whereas only three (19%) of 16 patients with larger parotid glands showed grade 2 xerostomia (P < 0.05). The mean volume of the parotid glands on CT-1 was 43.1 +/- 15.2 ml, but decreased significantly to 32.0 +/- 11.4 ml (74%) on CT-2 (P < 0.0001). CONCLUSIONS: Initial volumes of the parotid glands are significantly correlated with the grade of xerostomia in patients treated with IMRT. The volume of the parotid glands decreased significantly during the course of IMRT.     

Defects in muscarinic receptor-coupled signal transduction in isolated parotid gland cells after in vivo irradiation: evidence for a non-DNA target of radiation

Radiation-induced dysfunction of normal tissue, an unwanted side effect of radiotherapeutic treatment of cancer, is usually considered to be caused by impaired loss of cell renewal due to sterilisation of stem cells. This implies that the onset of normal tissue damage is usually determined by tissue turnover rate. Salivary glands are a clear exception to this rule: they have slow turnover rates (>60 days), yet develop radiation-induced dysfunction within hours to days. We showed that this could not be explained by a hypersensitivity to radiation-induced apoptosis or necrosis of the differentiated cells. In fact, salivary cells are still capable of amylase secretion shortly after irradiation while at the same time water secretion seems specifically and severely impaired. Here, we demonstrate that salivary gland cells isolated after in vivo irradiation are impaired in their ability to mobilise calcium from intracellular stores (Ca2+ i), the driving force for water secretion, after exposure to muscarinic acetylcholine receptor agonists. Using radioligand-receptor-binding assays it is shown that radiation caused no changes in receptor density, receptor affinity nor in receptor-G-protein coupling. However, muscarinic acetylcholine agonist-induced activation of protein kinase C alpha (PKCalpha), measured as translocation to the plasma membrane, was severely affected in irradiated cells. Also, the phorbol ester PMA could no longer induce PKCalpha translocation in irradiated cells. Our data hence indicate that irradiation specifically interferes with PKCalpha association with membranes, leading to impairment of intracellular signalling. To the best of our knowledge, these data for the first time suggest that, the cells' capacity to respond to a receptor agonist is impaired after irradiation.     

Advances in radiation therapy of head and neck cancer

Head and neck cancer is the fifth most common cancer in the USA. Although there have been major improvements in surgical and radiation techniques, the overall survival has not changed significantly in the last decade. The major changes occurring in recent years have been in the ability to preserve organs and to improve quality of life. The advances in radiation therapy include 3D conformal radiotherapy, intensity-modulated radiotherapy and, more recently, imaging-guided radiotherapy. In advanced head and neck cancer the addition of chemotherapy to radiation has concomitantly improved survival and facilitated higher rates of organ preservation. Clinical trials are needed to develop better strategies customized to subgroups defined by individual biological risk and imaging findings.     

Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists

Damage to salivary glands after radiotherapeutic treatment of head and neck tumours can severely impair the quality of life of the patients. In the current study we have investigated the early-to-late pathogenesis of the parotid gland after radiation. Also the ability to ameliorate the damage using pretreatment with adrenergic or muscarinic receptor agonists is studied. Rats were locally irradiated with or without i.p. pretreatment with phenylephrine (alpha-adrenoceptor agonist, 5 mg kg(-1)), isoproterenol (beta-adrenoceptor agonist, 5 mg kg(-1)), pilocarpine (4 mg kg(-1)), methacholine (3.75 mg kg(-1)) (muscarinic receptor agonists) or methacholine plus phenylephrine. Parotid salivary flow rate, amylase secretion, the number of cells and gland histology were monitored sequentially up to 240 days postirradiation. The effects were described in 4 distinct phases. The first phase (0-10 days) was characterised by a rapid decline in flow rate without changes in amylase secretion or acinar cell number. The second phase (10-60 days) consists of a decrease in amylase secretion and is paralleled by acinar cell loss. Flow rate, amylase secretion and acinar cell numbers do not change in the third phase (60-120 days). The fourth phase (120-240 days) is determined by a further deterioration of gland function but an increase in acinar cell number, albeit with poor tissue morphology. All drug pretreatments used could reduce radiation effects in phase I and II. The protective effects were lost during phase IV, with the exception of methacholine plus phenylephrine pretreatment. The latter combination of drugs ameliorated radiation-damage throughout the entire follow-up time. The data show that combined pre-irradiation stimulation of muscarinic acetylcholine receptors with methacholine plus alpha-adrenoceptors with phenylephrine can reduce both early and late damage, possibly involving the PLC/PIP2 second messenger pathways. This opens perspectives for the development of clinical applicable methods for long-term sparing of parotid glands subjected to radiotherapy of head and neck cancer patients.     

HPV与头颈癌转移的研究进展

转移是头颈癌复发与高度致死的重要原因。人乳头瘤病毒（human papillomavirus，HPV）感染是头颈癌发生的重要风险因素。与HPV阴性（-）头颈癌相比，HPV阳性（+）头颈癌更容易转移，目前其转移机制还未完全阐明。研究HPV相关头颈癌转移机制可为头颈癌治疗提供新思路，进一步改善患者预后。因此本文就HPV引起头颈癌转移的机制作一综述。     

Global and health-related quality of life after intensity-modulated radiation therapy for head and neck cancer

This study aims to evaluate the current literature regarding the effects of conventional radiation therapy (CRT) versus intensity-modulated radiation therapy (IMRT) on global quality of life (QoL) among patients treated for head and neck cancer. A PubMed literature review was performed. Only articles comparing global QoL scores in head and neck cancer patients treated with CRT versus IMRT were included. Studies were scrutinized for methodology, level of evidence and limitations. Outcomes were evaluated for external validity, level of evidence and applicability. Between 2005 and 2012, 14 eligible studies (six prospective, two randomized controlled trials) were identified. Although all presented data comment on the advantages of IMRT, differences in study design made comparisons difficult. The vast majority of these were also limited by relatively small sample sizes and heterogeneity with respect to patient and treatment-related characteristics. Although more robust evidence is needed in the future, the published data reasonably support the benefits of IMRT as compared with CRT (either 2D or 3D) in improving QoL, beginning at approximately 3–6 months post-treatment, and possibly potentiating with time up to 2 and 3 years.     

Gene therapy for head and neck cancer

The prognosis of patients with advanced head and neck cancer has not changed significantly in the last twenty years, despite concerted efforts to optimize treatment using conventional modalities such as surgery, radiotherapy and chemotherapy. Novel therapeutic approaches based on our increasing understanding of the molecular changes that underlie the development of cancer have the potential to alter this situation. Gene therapy involves the delivery of genetic sequences in to tumour or normal cells for a therapeutic purpose. A number of viral and non-viral vectors have been developed that have the ability to deliver therapeutic genes specifically to tumours. These therapeutic genes can exert their effects by correcting existing genetic abnormalities, by killing cells directly or indirectly through recruitment of the immune system. In this review, the various gene therapy strategies that are under development are presented with particular reference to the treatment of head and neck cancer.