外放疗联合个体化导板辅助 125I放射性粒子植入治疗晚期头颈部鳞癌

目的：探讨外放疗联合个体化导板辅助¹²⁵I放射性粒子植入治疗无法手术的头颈部鳞癌的可行性及不良反应。 方法：对17例因全身系统疾病而无法手术的头颈部鳞癌患者进行常规分割放疗联合个体化导板辅助¹²⁵I放射性粒子植入增量放疗。外放疗总照射剂量为50 Gy,放射性粒子匹配周缘剂量（matched peripheral dose, MPD）为80~120 Gy。 结果：通过肿瘤体积变化情况和临床表现评价治疗标准,17例患者治疗总有效率达到82.4%（14/17）,1例死于大出血。主要的不良反应包括：软组织坏死、局部出血及放射性黏膜炎和皮炎等,治疗过程未发生急性并发症与严重的放射性损伤。 结论：外放疗联合个体化导板辅助¹²⁵I放射性粒子植入治疗晚期头颈部鳞癌,是一种微创、有效、安全性高的治疗方案。     

125I放射性粒子植入计划定制研究

目的 定制¹²⁵I 放射性粒子植入计划的优选方案。方法 将¹²⁵I 粒子等间距植入直径为1、2和3 cm的3种球形模体和三径分别为1 cm×1 cm×2 cm、1 cm×1 cm×3 cm、1 cm×2 cm×2 cm、1 cm×2 cm×3 cm、1 cm×3 cm×3 cm、2 cm×2 cm×3 cm和2 cm×3 cm×3 cm的7种椭球形模体,粒子分布均匀对称,调整粒子活度和间距,使靶区剂量满足处方剂量D₉₀ 145 Gy,并实现尽可能适形均匀的剂量分布。初始粒子间距是1 cm,为改善靶区剂量分布适形度和均匀性,将粒子间距调整为0.75 cm。通过评价均匀性指数（HI）、靶区外体积指数（EI）和适形指数（CI）定制粒子植入优选方案。同时记录植入粒子活度和数目。结果 对直径1 cm的球形靶区,粒子间距1和0.75 cm 时HI分别为40.0%和55.9%,EI分别为98.3%和95.1%,CI均为0.44;对直径3 cm的球形靶区和1 cm×2 cm×2 cm的椭球形靶区,粒子间距1 cm植入方式的HI、EI和CI优于粒子间距0.75 cm 的植入方式。对其余靶区粒子间距0.75 cm植入方式的EI和CI均优于间距1 cm的植入方式,HI略小于间距1 cm的植入方式。粒子间距0.75和1 cm植入单颗粒子活度分别为17.0~27.8 MBq 和30.0~58.8 MBq,间距0.75 cm比间距1 cm多植入粒子2~10颗。结论 对于10种靶区,除直径为1 cm、3 cm的球形靶区和1 cm×2 cm×2 cm 的椭球形靶区以外,其余7种靶区0.75 cm 植入方式的剂量分布适形度更好,靶区外接受处方剂量体积更小,为粒子均匀植入的优选方案。     

头颈部125I放射性粒子植入术中及术后患者周围辐射安全评价

目的 对头颈部¹²⁵I粒子植入术中及术后患者周围辐射剂量进行监测和安全评价。方法 40名接受头颈部¹²⁵I粒子植入术的患者按照粒子植入部位分为面颈部组和口腔内组,手术时监测距其皮肤表面30 cm处不同方向的辐射剂量率,术后监测距其皮肤表面30、50和100 cm处不同方向上的辐射剂量率,对口腔内组分别记录患者张口以及闭口状态下的辐射剂量率,参考国家辐射安全标准进行分析研究。结果 手术中位于患者靶区侧的辐射剂量［(2.60±0.37 μSv)］明显大于处于患者颅顶侧［(0.28±0.05)μSv］或靶区对侧［(0.15±0.03)μSv)］(t=25.62、29.51, P＜0.05);术后口腔内组患者张口状态下距其正前方30和50 cm处的辐射剂量率［(21.71±0.92)和(9.50±0.38) μSv/h)大于闭口状态［(9.29±1.14)和(4.61±1 μSv/h)］,差异有统计学意义 (t=35.87、13.70, P＜0.05);而100 cm处分别为(1.54±0.05)和(1.34±0.45)μSv,差异无统计学意义(t=1.94, P >0.05)。面颈部组在距患者靶区侧30、50和100 cm处的辐射剂量率分别为(66.28±3.31)、(35.06±3.05)和(1.72±0.17) μSv/h,大于口腔内组［(52.46±3.54)、(20.78±2.01)和(1.55±0.13)μSv/h］(t=12.74、15.51、3.69, P< 0.05),两组靶区侧100与30 cm相比辐射剂量率减少(t=86.39、63.55、155.44,P＜0.05)。100 cm处面颈部组靶区侧的辐射剂量率为(1.72±0.17)μSv/h,口腔内组正前方张口状态为(1.55±0.13)μSv/h,闭口状态为(1.18±0.42)μSv/h,均符合国家辐射安全标准。结论 头颈部¹²⁵I粒子植入术后患者对医护人员及公众辐射影响很小,注意距离和接触时间以及接触方向可以实现辐射安全。     

经环甲膜植入125I粒子治疗中心性肺癌临床分析

2002年7月至2004年9月，笔者采用经环甲膜穿刺、置管，气道内悬挂^125I放射性微粒子（简称种子源），对19例中心性肺癌并发气道狭窄、肺不张者进行近距离低能量持续放疗，取得较好疗效，报道如下。     

放射性125I粒子离体照射模型的建立和测量

目的建立放射性^125I粒子离体照射模型,研究模型中离体细胞照射平面的剂量和剂量分布。方法应用14颗粒子环形排布的照射模型,用临床上常用的6711型^125I粒子。实验前随机抽取20%的粒子校正,应用TLD元件对模型进行测量。先用37MBq的^125I粒子照射6d,测量细胞平面受照剂量并计算初始剂量率;然后用同样活度的^125I粒子照射10d后测量,与用公式计算的照射剂量值进行比较。结果TLD标定：测量读数和照射剂量拟合为线性关系。单颗粒子活度测量值与出厂标定值相差〈±5%。照射6d测量细胞平面累积剂量为1.58Gy,计算初始剂量率为0.273Gy/d;照射10d的测量值和理论计算值分别为2.43和2.57Gy,两者相差5.76%。根据对模型的测量和计算,可推导出在不同的初始剂量率下受照剂量和照射时间的关系。结论建立的放射性125I粒子离体照射模型简便实用,可用于放射生物学实验研究。受照剂量与照射时间关系的建立,为今后开展放射性125I粒子相对生物效应的研究和对肿瘤细胞作用机制的研究奠定基础。     

125I放射性粒子组织置入治疗恶性肿瘤研究进展

放射治疗是恶性肿瘤的有效治疗方法之一,但传统外放射治疗存在许多弊端。随着放射性粒子的研制成功,特别是125I放射性粒子(简称125I粒子)内放射治疗的推广应用,其对肿瘤治疗的效果越来越受到人们的关注[1-3]。现将125I放射性粒子组织置入治疗恶性肿瘤的基础理论及近年来的研究进展介绍如下。     

125I粒子植入联合内分泌治疗前列腺癌疗效观察

目的 回顾性分析¹²⁵I粒子植入联合内分泌治疗T₃N₀M₀期前列腺癌的疗效和不良反应。方法 临床分期为T₃N₀M₀前列腺癌患者22例,行经直肠超声引导¹²⁵I粒子植入联合内分泌治疗。靶区最小周边剂量为140~160 Gy,尿道剂量<400 Gy。中位粒子数74颗(26~90颗),中位粒子活度1.55×10⁷ Bq(1.30×10⁷~1.85×10⁷)Bq。11例行去势手术,11例行药物去势联合抗雄激素治疗。结果 22例患者均顺利完成粒子植入治疗。5年无生化失败生存率为70.6%,总生存率为81.8%。2例于粒子植入术后12个月出现生化失败,1例在术后90个月出现生化失败,重新给予内分泌治疗。粒子植入治疗后1级、2级尿道不良反应发生率分别为54.5%、9.1%,1级和2直肠不良反应发生率分别为22.7%和9.1%,1例出现4级直肠反应。结论 放射性¹²⁵I粒子植入联合内分泌治疗T₃N₀M₀期前列腺癌创伤小、疗效好,可以考虑应用于不愿接受外放疗的患者。     

CT引导下125I粒子永久植入治疗肝转移癌

目的探讨CT引导下125I粒子植入治疗在肝转移癌治疗中的意义。方法 2007年8月～2008年10月31例结肠癌肝转移患者,共67个转移灶,均采用CT导向下125I放射性粒子植入,粒子植入之前采用治疗计划系统(treat-ment planning system,TPS)模拟布源或遵循Halarism的125I经验公式(mCi=Da×5),粒子按照0.5～1.0cm平面插植。在螺旋CT导向下将125I放射性粒子植入肝转移癌实质内及肿瘤边缘。结果治疗后2个月进行肿瘤影像学评价,31例患者中,完全缓解(complete remission,CR)7例,部分缓解(partial remission,PR)15例,稳定(no change,NC)9例。全组31例目前全部存活,随访时间最长14个月,最短6个月,近期平均生存期10.5个月。结论 CT导向下125I粒子植入治疗肝转移癌疗效确切、创伤小、并发症少,是一种比较安全、微创、有效的方法。     

脊柱转移癌经皮椎体成形术联合125I粒子植入治疗

经皮椎体成形术（percutaneous vertebroplasty，PVP）是在影像学技术（DSA机、X线或CT等）引导下应用特殊穿刺针经过皮肤穿刺到病变椎体，然后将骨水泥注入，加固病变椎体、恢复脊柱稳定性的一种介入新技术。笔者自2004年7月开展PVP联合^151I粒子植入椎体内治疗脊柱转移癌，发现局部抗肿瘤作用明显，现报道临床观察的初步结果。     

3D打印模板辅助CT引导放射性125I粒子植入治疗肿瘤专家共识

放射性粒子组织间永久植入治疗（简称粒子植入）肿瘤属于近距离范畴,它具有局部剂量高和周围正常组织损伤小的特点,已成为早期前列腺癌标准治疗手段之一。粒子植入借助超声、CT、MRI影像引导将放射性粒子送入到肿瘤靶区,因此,放射性粒子治疗兼具外科和介入治疗的特点。而粒子植入治疗的剂量学评估、危及器官剂量控制又隶属放射治疗范畴,因此,粒子治疗是跨学科、跨专业的技术。建立一支多学科合作团队,才有可能实现精准的粒子植入治疗。目前前列腺癌粒子植入技术已经非常成熟,而其他部位肿瘤粒子植入技术流程、标准尚处于研究阶段。本文主要基于3D打印模板技术建立起的规范和共识,内容包括：粒子物理学、剂量学、技术流程、适应证、不良反应。粒子治疗是非常有效的局部治疗手段,但是鉴于目前尚缺少大规模循证医学证据,还需要多中心的前瞻性、随机Ⅲ期临床研究,以及发表高水平文章,提高循证医学等级,确立粒子植入治疗在肿瘤综合治疗中的地位和作用。     

老年头颈癌患者125I粒子植入治疗后的生存质量研究

目的 评价老年头颈癌患者碘-125(¹²⁵I)粒子植入治疗后生存质量状况。方法 选择2005年至2011年就诊于本院因头颈癌行¹²⁵I粒子植入治疗的老年患者40例,采用QOL-RTI问卷对生存质量进行调查。评价其生存质量情况,并分析治疗后影响生存质量的因素。结果 40例入选患者,治疗后维持了良好的生存质量。老年舌根癌患者粒子植入后生存质量低于其他部位癌患者;老年患者功能状况和整体生存质量随年龄增加而降低;术后辅助¹²⁵I粒子植入治疗患者生存质量(QOL)高于未能完全切除或难以手术的患者;病理类型、粒子植入数量以及治疗后时长对患者生存质量无明显影响。结论 老年头颈癌患者行¹²⁵I粒子植入术后,维持有良好的生存质量。肿瘤靶区和临床分期是影响患者生存质量的重要因素。     

Efficacy and safety of CT-guided 125I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma after surgery and external beam radiotherapy: A 12-year study at a single institution

ObjectivesThe objective of this study was to evaluate the efficacy and safety of CT-guided radioactive ¹²⁵I seed implantation as a salvage treatment for locally recurrent head and neck soft tissue sarcoma (HNSTS) after surgery and external beam radiotherapy.Methods and MaterialsFrom December 2006 to February 2018, 25 patients with locally recurrent HNSTS after surgery and external beam radiotherapy were enrolled. All the patients successfully underwent CT-guided ¹²⁵I seed implantation. The primary end points included the objective response rate (ORR) and local progression-free survival (LPFS). The secondary end points were survival (OS) and safety profiles.ResultsAfter ¹²⁵I seed implantation, the ORR was 76.0%. The 1-, 3-, and 5-year LPFS rates were 65.6%, 34.4%, and 22.9%, respectively, with the median LPFS of 16.0 months. The 1-, 3-, and 5-year OS rates were 70.8%, 46.6%, and 34.0%, respectively, with the median OS of 28.0 months. Furthermore, univariate analyses showed that the recurrent T stage and histological grade were prognostic factors of LPFS, whereas only the histological grade was a predictor of OS. The major adverse events were skin/mucosal toxicities, which were generally of lower grade (≤Grade 2) and were well tolerated.ConclusionsRadioactive ¹²⁵I seed implantation could be an effective and safe alternative treatment for locally recurrent HNSTS after failure of surgery and radiotherapy. Recurrent T stage and histological grade were the main factors influencing the efficacy.     

Evaluation of suspected local recurrence in head and neck cancer: a comparison between PET and PET/CT for biopsy proven lesions

Background

¹⁸F-FDG PET has a high accuracy for re-staging of head and neck cancer. The purpose of this study was to determine whether the diagnostic accuracy can be further improved with integrated PET/CT.

Materials and methods

Forty-nine patients with a mean age of 59 ± 18 years were studied retrospectively. Histo-pathological verification was available either from complete tumor resection with or without lymph node dissection (n = 27) or direct endoscopic biopsy (n = 16) or ultrasound guided biopsy (n = 6). Two reviewers blinded to the pathological findings read all PET images in consensus. An experienced radiologist was added for the interpretation of the PET/CT images.

Results

Tissue verification was available for 110 lesions in 49 patients. Sixty-seven lesions (61%) were biopsy positive and 43 (39%) were negative for malignant disease. PET and PET/CT showed an overall accuracy for cancer detection of 84 and 88% (p = 0.06), respectively. Sensitivity and specificity for PET were 78 and 93% versus 84 (p = NS) and 95% (p = NS) with PET/CT. A patient-by-patient analysis yielded a sensitivity, specificity and accuracy for PET of 80, 56 and 76%, compared to 88% (p = NS), 78% (p = NS) and 86% (p = 0.06) for PET/CT.

Conclusion

The results of this study indicate that PET/CT does not significantly improve the detection of recurrence of head and neck cancer. However, a trend towards improved accuracy was observed (p = 0.06).     

Iodine-125 brachytherapy in the management of squamous cell carcinoma of the oral cavity and oropharynx

PurposeBrachytherapy is an acknowledged modality for treating head and neck cancers and has moved from low-dose-rate (LDR) to high-dose-rate remote afterloading to reduce staff exposure. Iodine-125 (¹²⁵I) is a low-energy source and can be used for LDR brachytherapy with minimal staff exposure. The results of treating with this isotope at Groote Schuur Hospital, Cape Town, are reported here.Methods and Materials¹²⁵I brachytherapy was used to treat 114 tumors from 1994 to 2010. Brachytherapy alone was used for 72 tumors, 39 postsurgery and 33 de novo. A brachytherapy boost together with external beam radiotherapy was used for 42 tumors, eight postsurgery and 34 de novo. Tumors were in the tongue, floor of mouth, soft palate, and tonsil, and mainly T1 or T2 classification. Brachytherapy was administered via an applicator or in plastic tubes implanted into the soft tissues or through the submandibular region.ResultsLocal control rates of 80.7% at 5 years and 80% at 10 years were comparable to LDR, pulsed-dose-rate, and high-dose-rate results with iridium-192, likewise the 5- and 10-year disease-specific survival rate of 74.3%. Complications of soft tissue ulceration occurred in 21 patients (18.4%) and healed spontaneously in 20 patients. There was no mandibular necrosis.Conclusions¹²⁵I can be used as the sole treatment or as a boost to external beam radiotherapy, with or without surgery for early mouth cancer. It combines the radiobiological advantages of LDR brachytherapy with minimum staff exposure. It is a flexible system. Local control is excellent with acceptable morbidity, and the treatment time is short.     

125I粒子治疗儿少期头颈部交界瘤的靶区与剂量设计

目的总结并评价儿少期头颈部交界性肿瘤125I放射性粒子植入方案的靶区与剂量设计。方法选择2010年1月至2018年12月间于北京大学口腔医院就诊经单纯125I放射性粒子组织间植入近距离治疗或联合手术治疗的儿少期交界性肿瘤患者11例, 以大体肿瘤靶区外扩0.5～1.0 cm为计划靶区, 处方剂量80～120 Gy, 活度为18.5 MBq, 全麻下按治疗计划将125I放射性粒子植入靶区。术后进行随访, 记录疗效及不良反应。评析粒子植入前、后剂量学参数以及局部控制率、客观缓解率和不良反应发生率。结果 11例儿少期患者粒子植入前、后剂量学参数差异无统计学意义(P>0.05)。随访33～131个月, 中位时间48个月。局部控制率100%, 完全缓解率71.4%, 客观缓解率100%, 急性不良反应率81.8%。结论 125I放射性粒子植入治疗儿少期头颈部交界瘤, 在合理的靶区及剂量设计下, 可获得满意的临床疗效且不良反应较低, 是一种可行的治疗手段。     

Clinical values for abnormal F-FDG uptake in the head and neck region of patients with head and neck squamous cell carcinoma

Purpose

Fluorine 18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) is used to identify index or second primary cancer (SP) of the head and neck (HN) through changes in ¹⁸F-FDG uptake. However, both physiologic and abnormal lesions increase ¹⁸F-FDG uptake. Therefore, we evaluated ¹⁸F-FDG uptake in the HN region to determine clinical values of abnormal tracer uptake.

Methods

A prospective study approved by the institutional review board was conducted in 314 patients with newly diagnosed HN squamous cell carcinoma (HNSCC) and informed consent was obtained from all enrolled patients. The patients received initial staging workups including ¹⁸F-FDG PET/CT and biopsies. All lesions with abnormal HN ¹⁸F-FDG uptake were recorded and most of those were confirmed by biopsies. Diagnostic values for abnormal ¹⁸F-FDG uptake were calculated.

Results

Abnormal ¹⁸F-FDG uptake was identified in primary tumors from 285 (91.9%) patients. False-negative results were obtained for 22.3% (23/103) T1 tumors and 2.2% (2/93) T2 tumors (P < 0.001). Thirty-eight regions of abnormal ¹⁸F-FDG uptake were identified in 36 (11.5%) patients: the thyroid (n = 13), maxillary sinus (n = 7), palatine tonsil (n = 6), nasopharynx (n = 5), parotid gland (n = 2) and others (n = 5). Synchronous SP of the HN was identified in eight (2.5%) patients: the thyroid (n = 5), palatine tonsil (n = 2), and epiglottis (n = 1). The sensitivity and specificity of ¹⁸F-FDG PET/CT for identification of SPs were 75.0% and 98.7%, respectively.

Conclusions

¹⁸F-FDG PET/CT is a reliable method for tumor staging and identify SP in HN region, promoting appropriate therapeutic planning. Additional examinations may be required to identify superficial or small-volume tumors.     

基于锥形束CT的头颈部肿瘤在线与离线结合图像引导放疗的研究

目的 分析锥形束CT(CBCT)在线摆位校正与离线自适应校正在减小头颈部肿瘤临床靶区(CTV)外放,从而减轻正常组织并发症中的作用.方法 16例行三维适形放疗的头颈部癌症患者入组.分次放疗前后均行在线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.放疗前后的配准差值分别作为放疗分次间误差和分次内误差,用于计算每例患者的系统误差和随机误差.利用CTV外放计算公式,计算在线校正前后CTV外放;以0.5 mm为允许的最大残余系统误差,计算离线校正系统摆位误差后CTV外放.结果 未经在线校正,左右、头脚和前后方向上群体化CTV外放分别为5.7mm、5.6 mm和7.3 mm;每分次放疗均行在线校正,3个方向上群体化CTV外放分别为1.7 mm、1.7 mm和2.3 mm;对系统摆位误差进行离线自适应校正,3个方向上群体化CTV外放分别为2.7 mm、2.5mm和3.6 mm.结论 基于CBCT图像分析的在线校正和离线自适应校正均能明显减小摆位误差,有助于缩小CTV外放,并有望减轻正常组织并发症.     

基于锥形束CT的头颈部肿瘤在线与离线结合图像引导放疗的研究

目的 分析锥形束CT(CBCT)在线摆位校正与离线自适应校正在减小头颈部肿瘤临床靶区(CTV)外放,从而减轻正常组织并发症中的作用.方法 16例行三维适形放疗的头颈部癌症患者入组.分次放疗前后均行在线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.放疗前后的配准差值分别作为放疗分次间误差和分次内误差,用于计算每例患者的系统误差和随机误差.利用CTV外放计算公式,计算在线校正前后CTV外放;以0.5 mm为允许的最大残余系统误差,计算离线校正系统摆位误差后CTV外放.结果 未经在线校正,左右、头脚和前后方向上群体化CTV外放分别为5.7mm、5.6 mm和7.3 mm;每分次放疗均行在线校正,3个方向上群体化CTV外放分别为1.7 mm、1.7 mm和2.3 mm;对系统摆位误差进行离线自适应校正,3个方向上群体化CTV外放分别为2.7 mm、2.5mm和3.6 mm.结论 基于CBCT图像分析的在线校正和离线自适应校正均能明显减小摆位误差,有助于缩小CTV外放,并有望减轻正常组织并发症.