Advances in treatment techniques: arc-based and other intensity modulated therapies

Treatment planning and radiation delivery techniques have advanced significantly during the past 2 decades. The development of the multileaf collimator has changed the scope of radiotherapy. The dynamic conformal arc technique emerged from traditional cone-based conformal arc therapies, which aim to improve target dose uniformity and reduce normal tissue doses. With dynamic conformal arc, the multileaf collimator aperture is shaped dynamically to conform to the target. With the advent of intensity-modulated radiotherapy (IMRT), the concept of arc therapy in combination with IMRT has enabled better-quality dose distributions and more efficient delivery. Helical tomotherapy has been developed to treat targets sequentially by modulating the beam intensity in each "slice" of the patient. Helical tomotherapy offers improved dose distributions for complicated treatments, such as whole-body radiation. Intensity-modulated arc therapy has been studied to modulate fluences in a cone beam rather than fan beam geometry to improve delivery efficiency. This article reviews arc-based IMRT, intensity-modulated arc therapy, and helical tomotherapy techniques. We compare the dosimetric results reported in the literature for each technique in various treatment sites. We also review the application of these techniques in specialized clinical procedures including total marrow irradiation, simultaneous treatment of multiple brain metastases, dose painting, simultaneous integrated boost, and stereotactic radiosurgery.     

国产放疗设备集成应用专家共识——鼻咽癌同质化IMRT设备篇

目的 针对鼻咽癌IMRT存在严重同质化不足的问题,从国产加速器和IGRT图像引导设备等方面进行专家共识推荐。方法 在放疗调查分析、现有临床研究数据、国内放疗设备的实际情况及共识专家委员会的建议,采用列举循证医学等级的方式,就国产加速器的集成应用展开讨论并达成推荐级别共识。结果 以鼻咽癌IMRT为例,对国产加速器和IGRT图像引导设备等方面多角度进行专家共识推荐,为放疗医务工作者在患者诊疗的各个流程中提供参考依据。结论 国产放疗设备集成应用专家共识设备篇的形成,在一定程度上推动基层医院与三甲医院在鼻咽癌IMRT的同质化发展。     

Actual dose variation of parotid glands and spinal cord for nasopharyngeal cancer patients during radiotherapy

PURPOSE: For intensity-modulated radiotherapy of nasopharyngeal cancer, accurate dose delivery is crucial to the success of treatment. This study aimed to evaluate the significance of daily image-guided patient setup corrections and to quantify the parotid gland volume and dose variations for nasopharyngeal cancer patients using helical tomotherapy megavoltage computed tomography (CT). METHODS AND MATERIALS: Five nasopharyngeal cancer patients who underwent helical tomotherapy were selected retrospectively. Each patient had received 70 Gy in 35 fractions. Daily megavoltage CT scans were registered with the planning CT images to correct the patient setup errors. Contours of the spinal cord and parotid glands were drawn on the megavoltage CT images at fixed treatment intervals. The actual doses delivered to the critical structures were calculated using the helical tomotherapy Planned Adaptive application. RESULTS: The maximal dose to the spinal cord showed a significant increase and greater variation without daily setup corrections. The significant decrease in the parotid gland volume led to a greater median dose in the later phase of treatment. The average parotid gland volume had decreased from 20.5 to 13.2 cm3 by the end of treatment. On average, the median dose to the parotid glands was 83 cGy and 145 cGy for the first and the last treatment fractions, respectively. CONCLUSIONS: Daily image-guided setup corrections can eliminate significant dose variations to critical structures. Constant monitoring of patient anatomic changes and selective replanning should be used during radiotherapy to avoid critical structure complications.     

Adenoid cystic carcinoma of trachea treated with adjuvant hypofractionated tomotherapy. Case report and literature review

Adenoid cystic carcinoma, also called cylindroma, is the second most common histological type of tracheal malignancy but represents 1% of all respiratory tract cancers. We report a case of a 59-year-old patient submitted to an incomplete resection of the trachea and subsequently treated with adjuvant tomotherapy. There have been no reports in the literature regarding intensity-modulated radiation therapy with linac or tomotherapy systems in adenoid cystic carcinoma of the trachea. The present clinical case demonstrates the feasibility of adjuvant intensity-modulated radiation therapy techniques for optimizing the dose coverage of the tumor bed while sparing surrounding normal tissues. A dosimetric comparison between the tomotherapy plan and a 3-dimensional conformal radiotherapy plan is also reported. We demonstrate that tomotherapy permits an increase in the dose per fraction without important acute adverse effects. At 24 months' follow-up, our patient shows no evidence of disease with negative histological findings.     

The current status of intensity-modulated radiation therapy in the treatment of nasopharyngeal carcinoma

Radiation therapy is the mainstay of treatment in nasopharyngeal carcinoma, alone or in combination with chemotherapy. In the early stage, it can be managed by radiotherapy alone. For locally advanced-stage disease, several meta-analyses have demonstrated the role of concurrent chemoradiotherapy. Conventional radiation therapy results in significant side effects, particular xerostomia, leading to poor quality of life. With the maturity of intensity-modulated radiation therapy in the recent 10 years, more and more evidences have shown the advantages of intensity-modulated radiation therapy over conventional radiation therapy, regarding the local-regional control, survival rate and quality of life. This article reviews the utilization of intensity-modulated radiation therapy in the management of nasopharyngeal carcinoma with respect to its technical advantages, clinical outcome, critical organ sparing and quality of life, and the dilemma in target delineation. In particular, an issue of treatment-related dysphagia will also be discussed.     

鼻咽癌调强放疗标准流程的同质化与优化策略

放疗是鼻咽癌最主要的治疗手段,放疗技术与水平对鼻咽癌预后至关重要。由于调强放疗设备结构的复杂性以及放疗临床要求的精确性,必然对调强放疗流程提出了更高的要求。目前我国各放疗单位在设备配置、人员结构组成等方面存在差距,放疗同质化有待加强。且随着放疗信息管理系统、数字医学及人工智能技术在放疗领域的应用,原有流程已经满足不了新型精确放疗技术的应用需要。本流程旨在依据现有鼻咽癌放疗流程的基础上,结合目前放疗领域的最新进展,建立新的标准流程推荐,有力保证放疗的规范化、同质化,并实现鼻咽癌调强放疗的个体化。     

鼻咽癌螺旋断层放射治疗过程中实际受照射剂量的研究

  目的  通过螺旋断层放射治疗（tomotherapy）系统的自适应模块,分析鼻咽癌患者靶区和危及器官的剂量在治疗过程中与初始计划的差异,为临床提供帮助。  方法  回顾性分析2014年2月至2015年2月昆明医科大学第一附属医院运用tomotherapy系统治疗的10例鼻咽癌患者,通过tomotherapy系统中的自适应模块和Mimvista 6.50软件的计算,将初始计划定义为Plan 1;进行图像引导患者总的实际受照射剂量定义为Plan 2。比较两项计划中肿瘤靶区及危及器官的剂量学差异。  结果  Plan 2中计划靶区体积（planning gross target volume,PGTV）的D98、D95的剂量较Plan 1分别下降11.91%、6.88%（P=0.001,P=0.006）。Plan 2中左侧腮腺的Dmean、D50较Plan 1分别增加42.23%、63.82%（P＜0.001、P=0.001）;Plan 2中右侧腮腺的Dmean、D50较Plan 1分别增加38.64%、66.76%（P=0.002,P=0.004）。Plan 2中脊髓的D2剂量较Plan 1也明显增加,增加了16.49%（P=0.026）。  结论  鼻咽癌患者在行tomotherapy过程中,非常有必要进一步纠正因解剖结构和摆位所带来的误差,保证放疗计划的精准性。      

Evaluating target coverage and normal tissue sparing in the adjuvant radiotherapy of malignant pleural mesothelioma: helical tomotherapy compared with step-and-shoot IMRT.

PURPOSE: To evaluate the potential of helical tomotherapy in the adjuvant treatment of malignant pleural mesothelioma and compare target homogeneity, conformity and normal tissue dose with step-and-shoot intensity-modulated radiotherapy. METHODS AND MATERIALS: Ten patients with malignant pleural mesothelioma who had undergone neoadjuvant chemotherapy with cisplatin and permetrexed followed by extrapleural pneumonectomy (EPP) were treated in our department with 54 Gy to the hemithorax delivered by step-and-shoot IMRT. A planning comparison was performed by creating radiation plans for helical tomotherapy. The different plans were compared by analysing target homogeneity using the homogeneity indices HI(max) and HI(min) and target conformity by using the conformity index CI(95). To assess target coverage and normal tissue sparing TV(90), TV(95) and mean and maximum doses were compared. RESULTS: Both modalities achieved excellent dose distributions while sparing organs at risk. Target coverage and homogeneity could be increased significantly with helical tomotherapy compared with step-and-shoot IMRT. Mean dose to the contralateral lung could be lowered beyond 5 Gy. CONCLUSIONS: Our planning study showed that helical tomotherapy is an excellent option for the adjuvant intensity-modulated radiotherapy of MPM. It is capable of improving target coverage and homogeneity.     

三种放疗技术对早期鼻咽癌颈部皮肤设定限制剂量差异研究

目的 比较固定野dIMRT、VMAT和HT技术在早期鼻咽癌放疗过程中颈部皮肤受量情况。方法 选取 16例完成放疗的早期鼻咽癌病例,将颈部外轮廓内缩3 mm生成皮肤。分别以传统方式(TP组)和将颈部皮肤作为OAR (NP组)进行剂量限制设计计划。统计各组计划中颈部皮肤 Dmean、V5—V70。对同一放疗技术的两组计划行配对t检验;对3种放疗技术的同一处理方法三组行方差分析。结果 HT组皮肤 Dmean、V5、V10、V30—V70均高于dIMRT和VMAT组(P=0.00、0.00、0.00、0.00、0.00、0.00、0.00、0.02)。dIMRT技术NP组皮肤 Dmean、V10—V60较TP组分别降低7%、8%、22%、25%、38%、59%、85%(P=0.00、0.00、0.00、0.00、0.00、0.00、0.00);VMAT技术NP组皮肤 Dmean、V20—V40较TP组分别降低4%、19%、29%、34%(P=0.02、0.01、0.02、0.01);HT技术NP组皮 肤V30—V70较TP组分别降低20%、29%、50%、67%、100%(P=0.00、0.00、0.00、0.00、0.03)。结论 早期鼻咽癌放疗计划设计中HT较dIMRT和VMAT引起的颈部皮肤受量高,dIMRT和VMAT结果近似;在进行早期鼻咽癌计划设计时将颈部皮肤作为OAR进行剂量限制可明显降低颈部皮肤受量。     

局部晚期鼻咽癌新辅助化疗研究进展

鼻咽癌的治疗手段是以放射治疗为主的综合治疗,随着调强放疗等精确放疗技术和放化综合治疗的广泛应用,初治鼻咽的局部控制率已经提高到90%以上。为了提高局部晚期鼻咽癌的治愈率、降低复发或远处转移,放疗与化疗的结合一直是学者们研究热点。由于同步放化疗已成为局部晚期鼻咽的标准治疗,新辅助化疗是鼻咽癌综合治疗研究的热点,新辅助联合同步放化疗是否获益一直存在争议。同时调强放疗的大量应用,同步化疗的地位受到怀疑,新辅助化疗在调强时代能否替代同步化疗及新辅助化疗后靶区应如何勾画值得进一步研究。因此,本文就新辅助化疗治疗局部晚期鼻咽癌的进展进行综述。     

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

PURPOSE: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. METHODS AND MATERIALS: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. RESULTS: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. CONCLUSION: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.     

Advances in nasopharyngeal carcinoma

PURPOSE OF REVIEW: Intergroup 0099 established the role of concurrent chemotherapy with radiation therapy in the treatment of locally advanced nasopharyngeal carcinoma, but its reproducibility was unclear and chemotherapy compliance was poor. Multiple concurrent chemoradiation phase III trials were initiated in response to the Intergroup trial, and technologic advances in radiotherapy were explored to improve the therapeutic ratio. This review highlights recent advances in the management of nasopharyngeal carcinoma as a result of these endeavors. RECENT FINDINGS: Five randomized phase III trials confirmed the benefit of concurrent chemoradiation over radiation therapy alone, firmly establishing concurrent chemoradiation as the standard of care in locally advanced nasopharyngeal carcinoma. Each of these studies used conventional radiation therapy and noted an increase in toxicity over radiation therapy alone. Intensity-modulated radiation therapy is an advanced form of three-dimensional conformal radiotherapy which allows delivery of high doses of radiation to the tumor while sparing adjacent normal tissues, leading to improved local control and decreased radiation therapy-induced toxicities. Distant metastasis remains a significant problem despite intensity-modulated radiation therapy. Taxane-based induction chemotherapy seems promising in phase II studies. Targeted therapies remain a major area of interest and require further investigation. SUMMARY: Cisplatin-based concurrent chemoradiation followed by adjuvant chemotherapy is the standard of care for locally advanced nasopharyngeal carcinoma. Intensity-modulated radiation therapy has undergone a rapid evolution and is replacing conventional radiation therapy in many institutions. A multidisciplinary effort is under way to explore more effective systemic therapy to improve the distant metastasis free rates.     

IMRT、VMAT及HT技术在肺癌SBRT应用中的比较

肺癌立体定向放疗的主要技术包括调强放疗(IMRT)、容积旋转调强放疗(VMAT)和螺旋断层放疗(HT).3种技术在靶区适形度及剂量均匀性方面,HT和VMAT要优于IMRT,但HT和VMAT技术会增加肺的低剂量区受照体积.VMAT较其他两种技术可明显缩短治疗时间.目前,对于不同位置、不同分期的肺部肿瘤,如何个体化地选择最佳放疗技术仍存有一定的争议.     

鼻咽癌不同外照射设野放疗后局部区域复发部位的分析

[目的]探讨不同外照射设野放疗后局部区域复发部位的特点,为临床合理设野提供参考。[方法]对2002年1月￣2004年12月131例鼻咽癌复发病人,按传统、常规、三维适形放疗和调强放射治疗三种设野分别统计局部区域复发部位,并进行比较分析。[结果]常规设野在颈动脉鞘复发低于传统设野(32.4%vs.52.5%,P<0.05),而在单纯鼻咽复发、颅底复发、上颈淋巴结复发无明显差异(P>0.05)。三维及调强放疗组8例中6例病人局部复发,3例病人区域淋巴结复发。[结论]鼻咽癌放疗后局部区域复发以颈动脉鞘区、颅底及颈部为主;常规设野符合鼻咽癌的临床行为特性及剂量学原则,与传统设野相比,显示出一定的优势;三维和调强放疗具有潜在的优势,但还需要进一步的病例积累后才能得出结果。     

鼻咽癌放疗后复发再程调强放疗的疗效分析

目的　研究鼻咽癌放疗后复发再程调强放疗的疗效及影响预后的因素。方法　回顾性分析６２例鼻咽癌放疗后复发患者,男性４６例,女性１８例,中位年龄４９岁（３７～６５岁）,中位复发时间为２５个月（１０～５７个月）。全组患者均行调强放疗,肿瘤靶体积ＧＴＶ总剂量为６０～７０Ｇｙ,每次分割剂量１.８～２.３Ｇｙ。结果　全组患者的中位随访时间为１４个月,１、３年生存率分别为６２.２％和４１.８％。至随访截止日期,死亡２８例,再复发３例,再复发同时转移２例,转移５例。单因素分析结果显示,仅化疗（Ｐ＝０.００３）与生存期相关;多因素分析提示,化疗（Ｐ＝０.０００）和ＧＴＶ体积（Ｐ＝０.０１９）是影响复发鼻咽癌的独立预后因素。毒副反应可耐受。结论　鼻咽癌放疗后复发患者再程调强放疗有效、可靠,化疗与ＧＴＶ体积是影响预后的主要因素。     

Tomotherapy

Tomotherapy is delivery of intensity-modulated, rotational radiation therapy using a fan-beam delivery. The NOMOS (Sewickley, PA) Peacock system is an example of sequential (or serial) tomotherapy that uses a fast-moving, actuator-driven multileaf collimator attached to a conventional C-arm gantry to modulate the beam intensity. In helical tomotherapy, the patient is continuously translated through a ring gantry as the fan beam rotates. The beam delivery geometry is similar to that of helical computed tomography (CT) and requires the use of slip rings to transmit power and data. A ring gantry provides a stable and accurate platform to perform tomographic verification using an unmodulated megavoltage beam. Moreover, megavoltage tomograms have adequate tissue contrast and resolution to provide setup verification. Assuming only translational and rotational offset errors, it is also possible to determine the offsets directly from tomographic projections, avoiding the time-consuming image reconstruction operation. The offsets can be used to modify the leaf delivery pattern to match the beam to the patient's anatomy on each day of a course of treatment. If tomographic representations of the patient are generated, this information can also be used to perform dose reconstruction. In this way, the actual dose distribution delivered can be superimposed onto the tomographic representation of the patient obtained at the time of treatment. The results can be compared with the planned isodose on the planning CT. This comparison may be used as an accurate basis for adaptive radiotherapy whereby the optimized delivery is modified before subsequent fractions. The verification afforded tomotherapy allows more precise conformal therapy. It also enables conformal avoidance radiotherapy, the complement to conformal therapy, for cases in which the tumor volume is ill-defined, but the locations of sensitive structures are adequately determined. A clinical tomotherapy unit is under construction at the University of Wisconsin.     

Intensity-modulated radiation therapy (IMRT) dosimetry of the head and neck: a comparison of treatment plans using linear accelerator-based IMRT and helical tomotherapy

PURPOSE: To date, most intensity-modulated radiation therapy (IMRT) delivery has occurred using linear accelerators (linacs), although helical tomotherapy has become commercially available. To quantify the dosimetric difference, we compared linac-based and helical tomotherapy-based treatment plans for IMRT of the oropharynx. METHODS AND MATERIALS: We compared the dosimetry findings of 10 patients who had oropharyngeal carcinoma. Five patients each had cancers in the base of the tongue and tonsil. Each plan was independently optimized using either the CORVUS planning system (Nomos Corporation, Sewickly, PA), commissioned for a Varian 2300 CD linear accelerator (Varian Medical Systems, Palo Alto, CA) with 1-cm multileaf collimator leaves, or helical tomotherapy. The resulting treatment plans were evaluated by comparing the dose-volume histograms, equivalent uniform dose (EUD), dose uniformity, and normal tissue complication probabilities. RESULTS: Helical tomotherapy plans showed improvement of critical structure avoidance and target dose uniformity for all patients. The average equivalent uniform dose reduction for organs at risk (OARs) surrounding the base of tongue and the tonsil were 17.4% and 27.14% respectively. An 80% reduction in normal tissue complication probabilities for the parotid glands was observed in the tomotherapy plans relative to the linac-based plans. The standard deviation of the planning target volume dose was reduced by 71%. In our clinic, we use the combined dose-volume histograms for each class of plans as a reference goal for helical tomotherapy treatment planning optimization. CONCLUSIONS: Helical tomotherapy provides improved dose homogeneity and normal structure dose compared with linac-based IMRT in the treatment of oropharyngeal carcinoma resulting in a reduced risk for complications from focal hotspots within the planning target volume and for the adjacent parotid glands.     

局部晚期鼻咽癌的治疗研究进展

鼻咽癌是我国一种高发的恶性肿瘤,尤其在华南地区,其中约四分之三的患者诊断时即为局部晚期。其中调强放疗和全身化疗是目前鼻咽癌患者的重要治疗方法,但大部分患者治疗后仍会复发或转移。而同期放化疗后辅助性化疗或诱导化疗后同期放化疗是目前临床较常用的治疗方案,而其他新的治疗方法,如靶向治疗、免疫治疗、节律化疗等也为治疗提供了更多的选择,有望进一步提高患者的生存率。因此,本文就局部晚期鼻咽癌的治疗研究进展进行综述。