头颈部肿瘤涎腺放射性损伤的防治研究进展

放射性涎腺损伤是头颈部肿瘤患者放射治疗后最常见的并发症之一,表现为口腔疼痛,说话、吞咽困难等症状,严重影响患者的生存质量。因此,涎腺放射性损伤的防治十分重要。本文从放疗保护药物、放疗技术、分子生物学等方面,针对头颈部肿瘤涎腺放射性损伤的预防与治疗予以综述。     

CT-guided lymphoscintigraphy in patients with squamous cell carcinoma of the head and neck: a feasibility study

Accurate knowledge of lymphatic drainage facilitates planning of surgery for patients with squamous cell carcinoma of the head and neck. The aim of this study was to evaluate the feasibility of a new injection technique for lymph node detection in patients with squamous cell carcinoma of the hypopharynx and larynx, in whom simple peritumoural injection is hampered by the tumour localisation. Computed tomography (CT)-guided lymphoscintigraphy was performed in a total of 13 patients with squamous cell carcinoma of the hypopharynx and larynx who could not be injected by simple visual inspection. In a first step, contrast medium-enhanced axial 5-mm-thick CT slices of the neck were obtained. After tumour localisation on these CT images, 1–2 ml contrast medium and, in the event of appropriate distribution, subsequently 50 MBq technetium-99m colloid were injected at one to three peritumoural sites under CT guidance. Peritumoural tracer distribution was controlled by thin-slice CT. Subsequently, planar scintigrams from anterior, right and left lateral views were obtained. In all patients, peritumoural colloid application was feasible, as shown on control CT scans. Post injection, neither severe nor minor complications were noted. The patients complained of only low pain sensations with an average score of 1.8 on a pain scale from 0 to 10. Lymphatic drainage was identified in nine of the 13 patients, with a total of 14 detected lymph nodes. In six patients, ipsilateral sentinel lymph nodes were visualised; bilateral sentinel lymph nodes were identified in one patient and contralateral lymphatic drainage was observed in two patients. CT-guided lymphoscintigraphy is a feasible and minimally invasive diagnostic tool for sentinel lymph node detection in patients with squamous cell carcinoma of the hypopharynx and the larynx. In contrast to endoscopic colloid injection under general anaesthesia, this technique seems to be a well-tolerated method for lymphatic mapping prior to surgical procedures.     

头颈部肿瘤放疗相关口腔并发症和治疗

放疗是头颈部肿瘤患者常见的治疗方式。头颈部放疗常会导致口腔颌面部并发症, 因该部位组织结构复杂, 发病机制多样, 现有的治疗方案和研究进展较为局限。本文重点对最常见的放射性口腔黏膜炎、放射性唾液腺损伤及放射性龋齿进行系统总结, 回顾了现有发病机制假说、治疗及研究进展, 以期为深入研究相关病理机制和新的预防、治疗手段提供一定的参考。     

头颈部恶性肿瘤放疗后颈动脉狭窄的研究进展

头颈部恶性肿瘤是常见的恶性肿瘤,放射治疗是头颈部恶性肿瘤的重要治疗手段之一。随着治疗手段的进步,患者生存期明显延长,同时放疗引起的颈动脉狭窄也越来越受到医生及患者的关注。放疗引起的颈动脉狭窄是多种因素作用的结果,目前应用比较广泛的检查手段为彩色超声多普勒及颈动脉听诊,经皮血管成形术及支架植入术为主要的治疗手段。笔者主要针对头颈部恶性肿瘤放疗后引起颈动脉狭窄的发病率、发病机制、相关危险因素、诊断及治疗原则等方面进行综述。     

The impact of missed fractions in head and neck radiotherapy and how they can be minimised

Radiotherapy is an effective treatment for cancer, especially in cases of early stage disease, hence its continued routine use in Oncology. Overall treatment time is a significant factor which influences the efficacy of radiotherapy treatment. The accelerated reproduction of tumour clonogenic cells is considered to be a major contributory cause for reduced local control when treatment time is extended without dose compensation.It has been reported that even a one day gap can be damaging to treatment outcome with a reduction in local control being estimated at 1.4% per day of missed radiotherapy. With recent treatment compliance rates of 48.9% being observed in head and neck radiotherapy patients these factors provide the rationale for such a review. This paper reviews the current literature on the impact of missed fractions in radiotherapy for SCC head and neck and provide recommendations as to how missed fractions can be minimised.     

头颈部肿瘤放疗后吞咽困难防治的研究现状

吞咽困难是头颈部肿瘤放疗后常见的不良反应,在接受放化疗的头颈部肿瘤患者中,超过76%的患者会出现吞咽困难,轻者降低生活质量,重者可能危及生命。吞咽困难的形成与肿瘤分期、治疗方法和康复计划等相关,其预防和治疗是保障头颈部肿瘤患者生活质量的关键,但是目前临床防治措施明显不完善。笔者从吞咽系统的解剖及生理过程、放疗后头颈部肿瘤患者吞咽困难的形成原因、放疗对头颈部肿瘤患者吞咽困难发生发展过程的影响、吞咽困难的评估以及吞咽功能训练等方面进行综述,以期进一步为头颈部肿瘤患者放疗后出现吞咽困难的防治提供思路。     

Evaluation of diagnostic abilities of Ga-SPECT for head and neck lesions

OBJECTIVE: Single-photon emission computed tomography (SPECT) using gallium (Ga) has been frequently used for diagnosing head and neck tumors in patients. Although the usefulness of Ga-SPECT is well known, the degree of the increase in diagnostic ability with Ga-SPECT for head and neck tumors has not been reported. We compared the ability of the planar images of Ga scintigraphy, SPECT images of Ga scintigraphy, and CT images to diagnose head and neck primary tumors and neck metastases. METHODS: The subjects of this study were 167 patients with malignant head/neck lesions. For Ga scintigraphy, Ga-67-citrate (74 MBq) was injected via a cubital vein. Planar and SPECT images were taken 72 h after the Ga-67-citrate injection. The rate of detection of the primary lesions was compared first between SPECT and planar images then between SPECT and CT images. The rate of detection for each stage of disease according to the TNM classification was also analyzed. RESULTS: The rate of detection of primary lesions was 50% with planar imaging and 69% with SPECT. And similarly, regarding the rate of detection of lymph node metastases, there was a significant difference between planar imaging and SPECT. The rate of detection of primary lesions was 70% for both CT and SPECT. At T stage, the rates of detection of primary lesions with each imaging technique were 11% with planar imaging and 39% with SPECT, and 22% with CT for stage T1. CONCLUSIONS: This study revealed the marked superiority of SPECT images over planar images in terms of the ability to detect primary tumors and tumor metastasis to cervical lymph nodes. Furthermore, the primary T1 tumor detection rate of SPECT images was higher than that of CT images. On the basis of these results, the concomitant use of SPECT is highly recommended when Ga scintigraphy is performed to check for malignant head/neck tumors.     

Interstitial brachytherapy in the management of persistent head and neck disease after definitive external beam radiation therapy

PurposePersistent disease after definitive external beam radiation therapy for head and neck (H&;N) malignancies negatively impacts survival. In this series, the effectiveness of low-dose-rate brachytherapy in the management of persistent H&;N disease is explored.MethodsAll patients who received brachytherapy for persistent H&;N disease between 1987 and 2002 were identified. Tumor and treatment characteristics and toxicities were recorded. Progression-free survival and overall survival estimates were generated. The influence of prognostic factors was determined.ResultsTwelve patients were analyzable. Brachytherapy was given curatively (n = 4) in patients not amenable to surgery or in combination with surgical dissection to avoid carotid resection (n = 8). Seven patients had disease progression with a median time to progression of 11 months (95% confidence interval: 0–22.9). The only negative prognostic factor was time to re-treatment (brachytherapy >4 months) after definitive treatment (p = 0.003). Overall survival at 1 and 5 years was 50% and 21%, respectively. Toxicity was limited to one major complication (fistula) and five minor toxicities: low-grade radionecrosis (n = 2), cellulitis (n = 1), and wound dehiscence (n = 2).ConclusionIn patients with persistent disease, brachytherapy is an appealing re-treatment alternative. When combined with neck dissection, brachytherapy yields less morbidity than the surgical alternative of carotid resection.     

FDG-PET delayed imaging for the detection of head and neck cancer recurrence after radio-chemotherapy: comparison with MRI/CT

In advanced head and neck cancer, an organ-sparing approach comprising radiation therapy combined with intra-arterial chemotherapy has become an important technique. However, the high incidence of residual masses after therapy remains a problem. In this study, we prospectively evaluated the use of 2-[¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) delayed imaging for the detection of recurrence of head and neck cancer after radio-chemotherapy, and compared the FDG-PET results with those of magnetic resonance imaging (MRI) or computed tomography (CT). Forty-three lesions from 36 patients with head and neck cancer suspected to represent recurrence after radio-chemotherapy (median interval from therapy, 4 months) were studied. PET was performed at 2 h after FDG injection, and evaluated. The results were compared to those of contrast studies with MRI or CT performed within 2 weeks of the PET study, and to histological diagnosis (in all patients suspected of having recurrence) or clinical diagnosis. The lesion-based sensitivity (visual interpretation) and negative predictive value of FDG-PET (88% and 91%, respectively) were higher than those of MRI/CT (75% and 67% respectively). The specificity, accuracy and positive predictive value of FDG-PET (78%, 81% and 70%, respectively) were significantly (P<0.05) higher than those of MRI/CT (30%, 47% and 39% respectively). Three of six patients with false positive findings had post-therapy inflammation. Receiver operating characteristic (ROC) analysis showed that retrospective evaluation with the standardised uptake ratio yielded the best results (sensitivity 87.5%, specificity 81.5%), followed by visual interpretation and then the tumour/neck muscle ratio. An FDG-PET delayed imaging protocol yielded significantly better results for the detection of recurrence of head and neck cancer after radio-chemotherapy than MRI/CT. Because of the high negative predictive value of FDG-PET (91.3%), if PET is negative, further invasive procedures may be unnecessary.     

头颈部肿瘤放疗中转化医学相关机制的研究进展

头颈部肿瘤是目前世界上最常见的肿瘤之一,超过90%的头颈部肿瘤为鳞状细胞癌。放疗在头颈部肿瘤的治疗中显得尤为重要,目前国内治疗早期肿瘤可以单纯放疗为主,晚期肿瘤则选择综合性治疗。转化医学是近些年来新的研究重点,将科研过程及其成果与临床紧密结合,尤其体现在通过检测患者肿瘤组织中的基因突变靶点及基因单核苷酸多态性分型、mRNA基因定量表达,为临床提供靶向及个体化放疗的依据,能显著提高治疗的有效率。     

Retrospective analysis of self-reporting pain scores and pain management during head and neck IMRT radiotherapy: A single institution experience

AimsHead and neck carcinomas are relatively rare in the United Kingdom with an estimated 9000 cases diagnosed annually. However, pain associated with disease and treatment side effects such as oral mucositis present a major issue for therapy radiographers in providing effective care and maintaining radiotherapy treatment compliance, all factors that can compromise patient outcome if not managed appropriately.MethodThis retrospective analysis of self-reporting pain scores collected during a course of radiotherapy aims to assess the perceived pain intensity scores in 30 patients. Data was collected during radiographer review sessions held weekly to determine if any variables to perceived pain scores occurred during a course of radiotherapy.ResultsAs treatment progressed, the self-reporting pain scores within the cohort increased, in week one the total cohort pain score was 35, this increased to 114 in week 3 and in the final week had totalled 151. An escalation in pain was observed in week 3 of treatment possibly as a result of radiation induced inflammation alongside cytotoxic chemotherapy.ConclusionsThe findings of this study provide further evidence to an individualised approach to patient pain relief and providing regular on treatment reviews, thus maintaining patient comfort and ensuring continued treatment compliance.     

蛋白质摄入水平在头颈肿瘤放化疗中的应用研究

目的 探讨蛋白质摄入量对头颈肿瘤患者根治性放化疗期间黏膜损伤和营养状况的影响。 方法 选取2018年7月至2019年12月南京大学医学院附属鼓楼医院收治的72例头颈肿瘤患者的临床资料进行前瞻性研究。采用数字随机表法将患者分为2组,根据剔除标准,最终干预组纳入患者32例[男性27例、女性5例,年龄（51.67±12.92）岁]、对照组29例[男性23例、女性6例,年龄（56.03±8.26）岁]。干预组在常规膳食基础上接受在院蛋白质补充方案[补充乳清蛋白粉50 g/d,使总蛋白质摄入量达1.5~2.0 g/（kg·d）];对照组采用在院常规膳食方案[蛋白质摄入量为1.0~1.2 g/（kg·d）]。所有患者均采用根治性同步放化疗方案。比较治疗前后2组患者的黏膜损伤程度、营养指标变化、治疗疗效和相关并发症。计数资料的比较采用四格表χ2检验;两样本均数的比较采用成组t检验。 结果 2组患者在年龄、身高、血压、心率（t=−1.59~1.26）、性别、学历和病种（鼻咽癌与其他疾病）（χ2=0.01~0.45）方面的差异均无统计学意义（均P>0.05）。在口腔黏膜损伤方面,干预组患者的损伤程度低于对照组[16%（5/32）对38%（11/29）],且差异有统计学意义（χ2=3.913,P=0.04）;在营养指标方面,干预组与对照组比较,除了骨骼肌、体脂肪和血红蛋白外,干预组在体重[（−2.80±2.66） kg对（−4.85±2.35） kg,t=3.18,P＜0.01]、体重指数[（−1.00±0.95） kg/m2对（−1.81±0.89） kg/m2,t=3.38,P＜0.01]、握力[（5.59±4.20） kg对（2.59±5.32） kg,t=2.46,P=0.02]和血清白蛋白[（−1.40±3.37）g/L对（−3.07±2.92） g/L,t=2.06,P=0.04]指标的维持上均优于对照组。2组在疗效评价、腹泻、便秘和发热指标上的差异均无统计学意义（χ2=0.24~1.30,均P＞0.05）。 结论 在头颈肿瘤根治性放化疗中,补充蛋白质有缓解患者放射性黏膜损伤程度的作用,在保持患者营养指标上也具有优势。     

Dynamic MRI of tumours in head and neck with a contrast-enhanced FLASH-2D sequence

The purpose of this study was to evaluate the utility of a dynamic contrast enhanced FLASH-2D sequence for differential diagnosis of tumours in head and neck in 93 patients. Initially, the localization of the lesion and the selection of four representative slices for the dynamic study were obtained by a T2-weighted spin-echo sequence (TR 2000–3000 ms; TE 25/90 ms). After IV bolus injection of the contrast agent 10 images were acquired during a period of 3 min by a FLASH-2D sequence (TR 60 ms; TE 6 ms; flip angle 40° matrix 256 × 256; one acquisition). The percentage signal intensity (SI) increase (r) and the slope (S) of the curve were calculated on the basis of the SI time curve of the pathological lesion and of muscle. Inflammatory processes could be differentiated from malignant or benign tumours by means of a higher contrast enhancement. The time of the maximum SI was not specific for the different lesions. In comparison with muscle the maximum SI change was achieved earlier in a pathological process. Correspondence to: J. Mäurer     

吞咽功能训练在头颈部肿瘤放疗患者吞咽障碍中的应用进展

吞咽障碍是头颈部肿瘤（HNC）放疗后常见的不良反应之一,随着时间的延长病情加重,会导致患者营养不良、发生误吸性肺炎甚至死亡。虽然吞咽功能训练对HNC患者有一定的疗效,但训练方法尚未统一。笔者对HNC患者放疗后吞咽障碍的发生机制、影响因素、评估方法等进行综述,以期为HNC患者放疗后吞咽障碍的防治提供思路。     

Experience of high-dose-rate brachytherapy for head and neck cancer treated by a customized intraoral mold technique

Radiotherapy of head and neck cancer has become more successful with the advances in treatment modalities and use of a multidisciplinary approach. Higher quality treatment and a team approach to radiotherapy have thus been required for head and neck cancer. This study presents the clinical experience of high-dose-rate (HDR) brachytherapy for head and neck cancer treated by a customized intraoral mold technique. Two patients are reported for whom we created dental prostheses as the radiation carriers for HDR brachytherapy of their head and neck cancers. HDR brachytherapy with the dental prostheses reported here was feasible and effective for eradicating the head and neck cancer. It has been demonstrated that HDR brachytherapy using a customized intraoral technique can be a treatment option for patients who are not candidates for surgery or external irradiation. It is strongly suggested that specialized dentists are needed who are familiar with not only the anatomy and function of the head and neck region but also radiotherapy. Dental radiologists should take responsibility for constructing irradiation prostheses. If they do, they have the potential to improve the quality of life of patients who undergo radiotherapy for head and neck cancer.     

99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy

Purpose The purpose of this study was to determine the value of ^99mTc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. Methods TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6–8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (ΔU). Results In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean ΔU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. ΔU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum ΔU in primary tumour and in the lymph nodes. Conclusions Within the dose range of 0–8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic response.     

放射性125I粒子植入治疗头颈部肿瘤

目的 探讨超声或CT引导下放射性^125I粒子组织间植入治疗头颈部肿瘤的技术可行性和近期疗效。方法 40例头颈部癌和转移癌患者。4例采用全身麻醉，在CT引导下行^125I粒子植入术；36例采用局部麻醉，行超声引导下^125I粒子植入术。粒子针平行排列，间距1～1．5cm，原发肿瘤植入靶体积影像学边界外放lcm，转移瘤植入靶体积为影像学边界。粒子间距1cm。肿瘤周边匹配剂量（matched peripheral dose，MPD）90～145Gy，每颗粒子活度0．40～0．70mCi，每个病灶植入3～84颗粒子。5例患者术后1周加外放疗，每次200cGy，总剂量45～50Gy。术后24h拍头颈正侧位平片或CT，行质量验证。术后24～48h拍胸部x线片了解有无粒子移位或游走。结果 随访3～33月，10例舌癌3例完全缓解，3例部分缓解，3例稳定，1例进展；2例颈部淋巴结转移的患者经粒子治疗后完全缓解，局部控制率为60％，中位生存期11个月，1年和2年生存率分别为87．50％和35％。14例头颈部癌粒子治疗后，局部控制率为76．47％，中位生存期9个月，1年和2年生存率为66．08％和24％。16例头颈部转移癌粒子治疗后，局部控制率95．23％，中位生存期9个月，1年和2年生存率为54．55％和32．73％。没有1例发生严重的皮肤反应。结论 放射性^125I粒子粒子植入治疗头颈部癌疗效确切，尤其是为那些手术后或放疗复发患者提供了一种新的、可行的、安全和微创治疗手段。     

Manganese‐enhanced MRI of salivary glands and head and neck tumors in living subjects

Manganese‐enhanced MRI has previously been used for visualization of brain architecture and functional mapping of neural pathways. The present work investigated the potential of manganese‐enhanced MRI for noninvasive imaging of salivary glands in living subjects. Marked shortening of T₁ was observed in salivary glands of naïve mice (n = 5) 24–48 h after systemic administration of MnCl₂ (0.4 mmol/kg, intraperitoneally). Three‐dimensional MR microscopy confirmed selective contrast enhancement of salivary gland tissues post–MnCl₂ injection. Ectopic and orthotopic head and neck tumor xenografts also showed an increase in R₁ at 24 h following MnCl₂ injection (0.2 mmol/kg, intraperitoneally). However, tumor enhancement was minimal compared to salivary gland tissue. Salivary gland R₁ values were lower in mice bearing orthotopic head and neck tumors compared to naïve mice. These results demonstrate, for the first time, the usefulness of manganese‐enhanced MRI in the visualization of salivary glands and head and neck tumors in vivo. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: A treatment planning comparison

Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V₁₀, V₃₀, and V₅₀ values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life.     

In vivo proton MR spectroscopy of primary tumours,nodal and recurrent disease of the extracranial head and neck

Benign and malignant neoplasms as well as metastatic lymph nodes of 39 patients were examined using localized single voxel magnetic resonance spectroscopy (MRS) [repetition time (TR) 1500, echo time (TE) 135) at 1.5 T. New techniques with simultaneous correction of motion artefacts during the acquisition, three-dimensional saturation pulses, respiratory triggering and smaller volume of interest (VOI) size, were applied. Ratios of peak areas under the choline (Cho) and creatine (Cr) resonances were estimated in all cases and compared with those from samples of normal tissue. Ninety one spectra were acquired in 39 patients, 63 of which were suitable for further evaluation. The smallest VOI was 0.40 cm³. The Cho/Cr ratios in all malignant neoplasms (mean: 5.2, range: 1.7–17.8) were significantly elevated relative to those in the normal muscle structures (mean: 0.9, range: 0.2–1.4), while those in the benign neoplasms were elevated (mean: 24.4, range: 1.4–59.7) with respect to those in the malignant ones. The average Cho/Cr ratio in the metastatic lymph nodes was significantly higher (mean: 4.8, range: 3.3–5.6) than that for benign lymphoid hyperplasia (mean: 2.2, range: 1.0–3.0). MRS measurements were able to differentiate recurrent disease from post-therapeutic tissue changes in 11 out of 13 patients.