调强放疗计划多目标优化算法比较研究

目的 探讨多目标优化(MCO)算法在调强放疗计划优化中的应用。方法 随机抽取已接受治疗的10例前列腺癌和10例肺癌患者的调强治疗计划,这些计划都是基于直接子野优化算法进行优化的。在射野方向等设置条件不变前提下,改用MCO算法重新优化治疗计划。比较两种优化算法得到的剂量体积直方图参数、计划优化时间和机器跳数,并行配对t检验。结果 两种优化算法得到的调强计划均满足临床要求。与DMPO算法相比,在靶区剂量分布无差别下MCO算法使得前列腺癌计划中的直肠、膀胱及小肠受量均有不同程度降低,计划优化时间减少58%,机器跳数平均增加32%;在肺癌计划中肺、心脏和脊髓受量均有不同程度降低,计划优化时间减少59%,机器跳数平均增加11%。结论 与DMPO算法相比,MCO算法可显著降低危及器官受照剂量、缩短计划优化时间。     

前列腺癌重碳离子放疗计划与调强放疗计划的比较

目的比较前列腺癌重碳离子放疗（C-ion RT）与调强放疗（IMRT）在剂量学方面的差异。方法随机选取5例前列腺癌患者,分别设计4野共面的C-ion RT计划和7野共面的IMRT计划。剂量均采用百分剂量,95％的等剂量面必须包括100％的计划靶体积（PTV）。比较靶区剂量分布的适形度指数（CI）和异质性指数（IC）,根据剂量体积直方图（DVH）,比较相同剂量水平下C-ion RT计划与IMRT计划中周围器官及非靶区正常组织的照射体积。结果在C—-ion RT计划中,CI50%、CI94%、IC分别为3．36、1．20和0．03,与IMRT计划比较差异有统计学意义（P均〈0．01）,靶区剂量分布的CI和IC均优于IMRT计划。除了95％的剂量水平外,在10％、30％、50％、70％和90％剂量水平,采用C—ion RT均可明显减少直肠的受照射体积（P均〈0．05）,同时完全保护直肠的后壁;在任何剂量水平,C—ion RT可明显减少膀胱和非靶区正常组织的受照射体积（P均〈0．05）;在10％、20％、30％和40％剂量水平,C—ion RT可明显减少双侧股骨头的受照射体积（P均〈0．05）。结论在前列腺癌的放射治疗中,与IMRT计划相比,C—ion RT计划在剂量学方面有明显优势,C—ion RT的这些优势将能够进一步提高前列腺癌的局部控制率,减少放疗引起的并发症。     

鼻咽癌调强放疗剂量学边际效应研究

目的 分析鼻咽癌调强放疗计划参数中子野个数、面积、机器跳数的剂量学边际效应。方法 对2011—2012年间收治的17例鼻咽癌病例依次改变其中一个物理参数形式进行计划重新优化,从边际效应评价角度建立调强放疗计划技术投入和剂量学产出间的边际效应函数,并对3种优化方法剂量学结果进行统计分析。结果 17例患者原发灶计划的大体肿瘤体积在子野个数、面积、机器跳数优化下,平均适形指数的边际效应函数系数分别为0.02、0.74、0.55,平均均匀性指数的边际效应函数系数分别为0.56、0.89、0.73。危及器官的边际效应函数系数中左和右腮腺平均剂量的分别为0.01和0.02、－0.71和1.62、－0.40和0.71,左和右腮腺V₃₀的分别为0.01和0.01、0.08 和 0.05、0.02和0.03,脑干最大剂量的分别为0.13、1.20、1.72,脊髓最大剂量的分别为0.09、1.46、1.30、视交叉最大剂量的分别为0.03、0.22、0.01、左和右晶体最大剂量的分别为0.01和0.02、0.28和0.34、0.02和0.04。结论 鼻咽癌调强放疗计划优化中子野面积和机器跳数参数的设置对靶区和危及器官剂量的影响远大于子野个数。因此减少子野个数和优先给出较好的子野面积和机器跳数可以减少治疗时间,同时改善放射生物效应。     

两种子野分割算法制定食管癌调强计划比较

目的探讨Elekta Xio TPS(CMS5. 0)两种不同子野分割算法(Sliding Wnd和Smart Sequence)对食管癌患者(IMRT)计划有效性的影响。方法选取2017年8月至2018年8月间南方医科大学附属小榄医院收治的20例食管癌患者进行调强计划设计,初步进行通量优化,再采用两种子野分割算法行子野权重优化(segment weight optimization),比较二者的靶区和危机器官剂量分布、总子野数、机器跳数和治疗时间的差异。结果两种算法计算得到的IMRT计划比较,靶区及危机器官的剂量分布均能满足临床要求,采用Smart Sequence算法的计划总子野数平均减少27%,机器总跳数减少18%,治疗总时间二者没有太大区别。结论食管癌划在满足临床要求的前提下,采用SmartSequence算法得到的计划能显著减少总子野数和机器跳数。     

139例鼻咽癌调强放疗的临床研究

目的 观察调强放疗（IMRT）鼻咽癌的临床疗效、急性反应和晚期损伤。方法 初治鼻咽癌患者139例中，Ⅰ期9例，Ⅱ期30例，Ⅲ期71例，Ⅳa期29例；97例单纯根治性放疗，42例放化综合治疗。将鼻咽和颈部的靶体积划分为鼻咽大体肿瘤体积（GTVnx）、颈部大体肿瘤体积（GTVnd）、临床靶体积1（CTV1）和临床靶体积2（CT2）。GTVnx、GTVnd、CTV1、CTV2处方剂量分别为68、60-66、60、54Gv，均30分次。鼻咽和上颈部靶体积采用IMRT技术照射，下颈部靶体积采用下颈前野常规照射。采用Kaplan-Meier法进行生存分析，RTOG／EORTC标准评价急性反应和晚期损伤。结果 中位随访时间19个月，1、2,3年局部区域无进展和无远处转移生存率及总生存率分别为97．8％、94．4％、94．4％和90．8％、86．4％、81．0％及94．5％、91．0％、85．6％。多数患者仅表现为1～2级急性反应和0～1级晚期损伤，未观察到4级急性反应和晚期损伤。对随访超过2年的48例患者口干症状的动态观察表明，随着治疗后时间的延长口干逐渐减轻。DVH分析显示IMRT提高了靶体积照射总剂量和分次剂量，减少了危及器官受照总剂量和分次剂量。结论 IMRT初治鼻咽癌可获得理想的局部区域控制，对正常组织器官有较好的保护作用。远处转移是治疗失败的主要原因。     

初治鼻咽癌调强放疗的初步结果

目的分析调强放疗（IMRT）在初治鼻咽癌应用的初步结果.方法76例经病理证实的初治鼻咽癌患者接受了全程IMRT.根据1992年福州分期标准,Ⅰ期2例,Ⅱ期20例,Ⅲ期29例,Ⅳ期25例.采用多叶光栅的静态调强技术实施IMRT,采用的逆向治疗计划系统分别为TMS、CMS和Pinnacle.各靶区处方剂量均以其PTV定义给予,鼻咽肿瘤（GTV）和颈部淋巴结（GTV-LN）处方剂量为68～76Gy,鼻咽区域及上颈部临床靶区（CTV1）处方剂量为58～66Gy.下颈部锁骨上区域（CTV2）37例采用IMRT技术,处方剂量为50～60Gy,39例采用常规技术单前切线野照射.晶体、脑干、脊髓、视神经和视交叉的最高限量（99%体积低于此剂量）分别为8、54、40、54、54 Gy.7例合并同时化疗,4例IMRT后鼻咽局部予以立体定向放疗加量.采用Kaplan-Meier法计算生存率,RTOG标准评价急性副反应.结果中位随访期为10个月,全组死亡3例,分别死于鼻咽肿瘤未控大出血、肝转移和治疗相关并发症.1、2年总生存率分别为92%、92%;鼻咽和颈部1、2年局部控制率均为95%,4例出现了远处转移;1、2年无瘤生存率分别为95%、86%.急性反应以1、2级为主,其中唾液腺为99%,咽部和黏膜分别为88%和72%.GTV、GTV-LN、CTV1、CTV2的平均剂量均值分别为74.3、74.1、67.2、60.2Gy,平均低于95%处方剂量的靶区体积分别为0.58%、0.31%、0.67%、0.59%.左、右腮腺的中位剂量分别为33.9、34.0 Gy,晶体、脑干、脊髓、视神经、交叉最高剂量平均值分别为7.2、53.4、41.6、53.4、55.6 Gy.结论调强放疗技术能对初治鼻咽癌的各靶区达到很好的剂量分布,达到较高局部控制率,并降低了周围危及器官剂量和急性治疗反应,远期结果需进一步观察.     

鼻咽癌螺旋断层放疗与常规加速器调强放疗的剂量学比较

目的 通过比较鼻咽癌螺旋断层放疗与常规直线加速器静态调强治疗计划,研究其剂量学特性.方法 选10例鼻咽癌患者的CT图像,统一勾画靶区及正常器官后,分别传输至螺旋断层放疗、常规调强放疗逆向调强计划系统.统一给予肿瘤靶区(pGTV、PTVnd)处方剂量70 Gy分33次,亚临床病灶区(PTV1)60 Gy分33次,预防照射区(PTV2)54 Gy分33次.正常器官限制体积与剂量为腮腺V35＜50%,脑干＜54 Gy,脊髓＜45 Gy,晶体＜9 Gy等.对两组数据进行配对t检验.结果 两组计划均有较好靶区处方剂量分布,但螺旋断层放疗组的均匀性好于常规调强放疗组;PTV1平均剂量(63.84 Gy)也显著低于常规调强放疗组(70.30 Gy);腮腺平均剂量较常规常规调强放疗组低5.3Gy,V30及V35显著低于常规调强放疗组;喉-气管-食管的最大剂量也较常规调强放疗组明显降低.结论 在鼻咽癌调强放疗中,螺旋断层放疗较常规直线加速器静态调强放疗有更好的剂量均匀性及更陡峭的剂量梯度,并可更好地保护正常器官.     

122例鼻咽癌单纯根治性调强放疗疗效分析

目的分析单纯根治性调强放疗初治鼻咽癌的临床疗效。方法122例患者中，Ⅰ期11例，Ⅱ期34例，Ⅲ期62例，Ⅳa期15例。调强放疗计划与实施由PEACOCK系统完成。鼻咽大体肿瘤体积（GTVnx）处方剂量68Gy分30次；颈部转移淋巴结（GTVnd）60—66Gy分30次；临床靶体积1（CTV1）60Gy分30次；临床靶体积2（CTV2）54Gy分30次。采用Kaplan—Meier法进行生存分析和局部或区域控制率计算，Logrank检验组间差异。结果中位随访时间20个月（6～46个月）。全组1、2、3年总生存率分别为95．2％、91．4％、85．1％，无远处转移生存率分别为91．9％、88．6％和85．6％，局部和区域控制率分别为96．5％、93．2％、93．2％。T晚期（T3＋T4期）与T早期（T1＋T2期）的局部控制率比较差异无统计学意义（x^2=2．09，P=0．148）。颈淋巴结阳性与阴性的区域控制率比较差异无统计学意义（x^2=2．80，P=0．094），但其无远处转移生存率比较差异有统计学意义（x^2=8．48，P=0．004）。在治疗失败的17例中，局部和区域失败各占17．6％，远处转移占70．6％。结论单纯根治性调强适形放疗提高了初治特别是T晚期和颈淋巴结阳性鼻咽癌患者的局部和区域控制。治疗失败最主要的原因是远处转移，其发生率与颈淋巴结转移密切相关。     

鼻咽癌患者调强放疗与常规放疗所受剂量的比较

目的 估算和比较鼻咽癌患者在调强放疗和常规放疗过程中所受的辐射当量剂量.方法 使用热释光剂量仪对鼻咽癌患者在调强放疗和常规放疗过程中所受的周边剂量进行了测量,并推算出了患者全身当量剂量.结果 鼻咽癌患者靶区剂量给予70 Gy时调强放疗加速器的平均输出量为25235 MU,患者所受全身当量剂量为73.65 mSv;常规放疗加速器的平均输出量为8575 MU,患者所受全身当量剂量为15.28 mSv.结论 鼻咽癌调强放疗患者所受当量剂量高于常规放疗4.8倍.     

放疗后局部复发的鼻咽癌调强放疗的预后分析

目的回顾性分析和评价局部复发鼻咽癌调强放疗的临床结果和预后因素.方法共132例进入分析,其中男104例,女28例,中位年龄44.5岁（21～73岁）.全组中位复发时间为24个月（6～184个月）.依1992年福州分期标准再进行临床分期,Ⅰ、Ⅱ、Ⅲ、Ⅳa期分别为5、14、29、84例,其中T1、T2、T3、T4期各7、14、30、81例.22例同时伴有颈淋巴结复发.鼻咽大体肿瘤体积（GTV）处方剂量60～70Gy,分次剂量1.94～2.80Gy.60例接受了2～6个疗程的化疗.结果GTV中位体积为39.5 cm3（0.8～158.9 cm3）,治疗计划显示平均D95和V95分别达66.9Gy和98.3%,平均剂量和分次剂量均值分别为69.8、2.32Gy.全组中位随访时间12个月（2～47个月）.1、2、3年局部无进展生存率和总生存率分别为96.4%、88.4%、85.3%和65.9%、49.6%、41.6%.11例治疗后发生远处转移,47例治疗后出现鼻咽坏死或大出血,死亡57例.单因素及多因素分析显示分次剂量（P=0.016）和GTV体积（P=0.009）显著影响了患者的生存时间.结论IMRT可提高复发鼻咽癌患者的局部控制率和生存率.分次剂量和GTV体积为影响患者生存时间的独立预后因素.复发鼻咽癌治疗后的主要死亡原因为鼻咽坏死和大出血.     

调强放射治疗自动计划技术的研究进展

逆向调强放疗（intensity-modulated radiation therapy,IMRT）技术在保证靶区接收足够照射剂量的同时极大地降低了正常组织的受照剂量。在IMRT治疗计划的设计过程中,需要进行多次尝试与优化才能在提高靶区覆盖率与减少正常组织受照剂量的矛盾中找到平衡点。这种常规的计划设计过程十分繁杂,而且很大程度上依赖于设计者自身的经验,缺乏统一的规范和评判标准。因此,如果可以在复杂的优化过程之前就利用某些方法（例如自动计划算法）预测出最终的计划结果,将会提高计划的设计效率和质量。该研究将对放射治疗中自动计划技术的研究进展做一综述。     

Current status of intensity-modulated radiation therapy (IMRT)

External-beam radiation therapy has been one of the treatment options for prostate cancer. The dose response has been observed for a dose range of 64.8–81 Gy. The problem of external-beam RT for prostate cancer is that as the dose increases, adverse effects also increase. Three-dimensional conformal radiation therapy (3D-CRT) has enabled us to treat patients with up to 72–76 Gy to the prostate, with a relatively acceptable risk of late rectal bleeding. Recently, intensity-modulated radiation therapy (IMRT) has been shown to deliver a higher dose to the target with acceptable low rates of rectal and bladder complications. The most important things to keep in mind when using an IMRT technique are that there is a significant trade-off between coverage of the target, avoidance of adjacent critical structures, and the inhomogeneity of the dose within the target. Lastly, even with IMRT, it should be kept in mind that a “perfect” plan that creates completely homogeneous coverage of the target volume and zero or small dose to the adjacent organs at risk is not always obtained. Participating in many treatment planning sessions and arranging the beams and beam weights create the best approach to the best IMRT plan.     

Applicator-guided intensity-modulated radiation therapy

: We are introducing a novel method for delivering highly conformal dose distributions to cervical cancer tumors using external beam intensity-modulated radiation therapy. The method, termed applicator-guided intensity-modulated radiation therapy (AGIMRT), will use an applicator substitute placed in the vagina and uterus to provide spatial registration and immobilization of the gynecologic organs. The main reason for the applicator substitute will be to localize the fornices, cervix, and uterus with the expectation that the other nearby organs will also be reproducibly positioned with respect to the applicator substitute. Intensity-modulated radiation therapy (IMRT) dose distributions will be used as a substitute for high-dose-rate intracavitary brachytherapy procedures. The flexibility of IMRT will enable customized dose distributions that have the potential to reduce complications and improve local control, especially for locally advanced disease.

: To test the advantages of IMRT over intracavitary brachytherapy, volumetric scans of three cervical cancer patients were obtained with implanted CT-compatible applicators. IMRT dose distribution simulations using tomotherapy, were compared against intracavitary brachytherapy using cesium tubes to investigate the dosimetric differences of the two modalities. Because these tumor volumes do not image well on CT, the target volumes were defined as the isodose surface containing the traditional point A, defined as 2 cm superior to the vaginal fornices and 2 cm lateral to the intrauterine canal. One patient had a uterus that wrapped superior and anterior to the bladder. For this case, the cervix and uterus were selected as the target volume. To determine the potential for using an applicator substitute to localize internal organs, the posterior bladder and anterior rectal surfaces were localized relative to the colpostats. Comparisons of the colpostat-localized surfaces were conducted for two scan studies for 3 patients.

: The IMRT distributions covered the point-A isodose surfaces while reducing doses to the bladder and rectum. Brachytherapy showed extensive underdose regions in the target volume for the wrapped-around target. Spatial positioning was better than 0.7 and 1.3 cm in the rectum and bladder, respectively, indicating the potential that an applicator substitute may be able to localize these structures.

: AGIMRT has the potential for improving critical structure avoidance while maintaining highly reproducible and accurate internal organ registration found with brachytherapy.     

Use of benchmark dose-volume histograms for selection of the optimal technique between three-dimensional conformal radiation therapy and intensity-modulated radiation therapy in prostate cancer

PURPOSE: The aim of this study was to develop and validate our own benchmark dose-volume histograms (DVHs) of bladder and rectum for both conventional three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT), and to evaluate quantitatively the benefits of using IMRT vs. 3D-CRT in treating localized prostate cancer. METHODS AND MATERIALS: During the implementation of IMRT for prostate cancer, our policy was to plan each patient with both 3D-CRT and IMRT. This study included 31 patients with T1b to T2c localized prostate cancer, for whom we completed double-planning using both 3D-CRT and IMRT techniques. The target volumes included prostate, either with or without proximal seminal vesicles. Bladder and rectum DVH data were summarized to obtain an average DVH for each technique and then compared using two-tailed paired t test analysis. RESULTS: For 3D-CRT our bladder doses were as follows: mean 28.8 Gy, v60 16.4%, v70 10.9%; rectal doses were: mean 39.3 Gy, v60 21.8%, v70 13.6%. IMRT plans resulted in similar mean dose values: bladder 26.4 Gy, rectum 34.9 Gy, but lower values of v70 for the bladder (7.8%) and rectum (9.3%). These benchmark DVHs have resulted in a critical evaluation of our 3D-CRT techniques over time. CONCLUSION: Our institution has developed benchmark DVHs for bladder and rectum based on our clinical experience with 3D-CRT and IMRT. We use these standards as well as differences in individual cases to make decisions on whether patients may benefit from IMRT treatment rather than 3D-CRT.     

Using decision analysis to determine the cost-effectiveness of intensity-modulated radiation therapy in the treatment of intermediate risk prostate cancer

BACKGROUND: The specific aim of this study is to evaluate the cost-effectiveness of intensity-modulated radiation therapy (IMRT) compared with three-dimensional conformal radiation therapy (3D-CRT) in the treatment of a 70-year-old with intermediate-risk prostate cancer. METHODS: A Markov model was designed with the following states; posttreatment, hormone therapy, chemotherapy, and death. Transition probabilities from one state to another were calculated from rates derived from the literature for IMRT and 3D-CRT. Utility values for each health state were obtained from preliminary studies of preferences conducted at Fox Chase Cancer Center. The analysis took a payer's perspective. Expected mean costs, cost-effectiveness scatterplots, and cost acceptability curves were calculated with commercially available software. RESULTS: The expected mean cost of patients undergoing IMRT was $47,931 with a survival of 6.27 quality-adjusted life years (QALYs). The expected mean cost of patients having 3D-CRT was $21,865 with a survival of 5.62 QALYs. The incremental cost-effectiveness comparing IMRT with CRT was $40,101/QALYs. Cost-effectiveness acceptability curve analysis revealed a 55.1% probability of IMRT being cost-effective at a $50,000/QALY willingness to pay. CONCLUSION: Intensity-modulated radiation therapy was found to be cost-effective, however, at the upper limits of acceptability. The results, however, are dependent on the assumptions of improved biochemical disease-free survival with fewer patients undergoing subsequent salvage therapy and improved quality of life after the treatment. In the absence of prospective randomized trials, decision analysis can help inform physicians and health policy experts on the cost-effectiveness of emerging technologies.     

鼻咽癌调强放射治疗后发生椎动脉狭窄的危险因素

目的 探讨鼻咽癌调强放射治疗后发生椎动脉狭窄的危险因素。方法 回顾性分析2013年8月—2017年8月在广西柳州市工人医院就诊的148例鼻咽癌患者的临床资料。采用彩色多普勒超声检测双侧椎动脉血管内径、收缩期峰值流速及舒张末期血流速度以评估其狭窄情况，采用Logistic回归分析放射治疗后椎动脉狭窄的相关因素。结果 放疗后椎动脉狭窄发生率较放疗前高（47.3% vs 8.1%，P<0.001）。单因素分析显示，高血压、吸烟、高脂血症和椎动脉平均受照射剂量与椎动脉狭窄有关（均P<0.05）。多因素分析显示，椎动脉平均受照射剂量>60 Gy（OR=3.130，95%CI：1.417~6.914，P=0.005）、高脂血症（OR=2.549，95%CI：1.118~5.812，P=0.026）、高血压（OR=2.407，95%CI：1.130~5.127，P=0.023）、吸烟（OR=1.041，95%CI：1.006~1.077，P=0.022）是椎动脉狭窄的独立危险因素。结论 椎动脉平均受照射剂量>60 Gy、高脂血症、高血压和吸烟是鼻咽癌患者调强放射治疗后椎动脉狭窄的危险因素，应采取相应措施进行防治。     

Spinal cord planning risk volumes for intensity-modulated radiation therapy of head-and-neck cancer

PURPOSE: To assess planning organ at risk volume (PRV) margins of the spinal cord in intensity-modulated radiotherapy (IMRT) of oropharyngeal cancers, by modeling the effect of geometric uncertainties to estimate the probability of the spinal cord receiving a particular dose. METHODS AND MATERIALS: Five patients with oropharyngeal cancer were treated by IMRT with simultaneous doses of 66 Gy (gross disease) and 54 Gy (subclinical disease) in 30 fractions. Spinal cord doses were limited to 45 Gy. The probability, due to random and systematic patient positioning uncertainties (3-mm standard deviation), of the cord receiving a particular dose was determined. The effect of an on-line setup correction protocol was also modeled. RESULTS: The mean probability of a maximum spinal cord dose of 45 Gy was 1%, with a 6-mm PRV margin. The mean probability of a maximum dose exceeding 40 Gy was 37% (range, 13-77%); this probability is reduced with a setup correction protocol. CONCLUSION: A spinal cord PRV generated with a 6-mm margin leads to a 99% probability of maintaining the maximum spinal cord dose below 45 Gy. The application of an on-line setup correction protocol reduces the cord dose by approximately 5 Gy.     

Beam angle optimization and reduction for intensity-modulated radiation therapy of non-small-cell lung cancers

PURPOSE: To optimize beam angles and reduce the number of beams used for intensity-modulated radiation therapy (IMRT) of non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: An exhaustive search scheme was used to perform beam angle optimization (BAO) for IMRT of NSCLC. This approach involved intercomparison of all possible beam angle combinations and selection of the best angles based on the scores or costs of the objective functions used in the treatment plan optimization. Ten Stage III NSCLC cases were selected to evaluate the BAO algorithm and dosimetry benefits of IMRT-BAO. IMRT plans using five or seven coplanar beams were optimized and compared with those using nine equal-spaced beams. Results of BAO were also compared between plans using different numbers of beams with or without fluence modulation. RESULTS: Each anatomic structure, e.g., tumor or lung, had its own preferred beam angles. Thus, BAO required appropriate balance of competing objective functions. Plans using fewer angles (five or seven beams) could achieve plan quality similar to those using nine equal-spaced beams, however with reduced monitor units and field segments. The number of beams used for the treatment (five vs. seven) and the fluence modulation (open or IMRT beams) did not have a significant impact on the results of the BAO. CONCLUSIONS: Use of fewer beams (e.g., five) for lung IMRT could result in acceptable plan quality but improved treatment efficiency. A multiresolution search scheme could be developed for BAO using fewer and nonmodulated beams to reduce the computation cost of BAO.     

Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: update of the Memorial Sloan-Kettering experience

PURPOSE: We previously demonstrated that intensity-modulated radiation therapy (IMRT) significantly improves radiation dose distribution over three-dimensional planning for nasopharynx cancer and reported positive early clinical results. We now evaluate whether IMRT has resulted in improved outcomes for a larger cohort of patients with longer follow-up. METHODS AND MATERIALS: Since 1998, all 74 patients with newly diagnosed, nonmetastatic nasopharynx cancer were treated with IMRT using accelerated fractionation to 70 Gy; 59 received a hyperfractionated concomitant boost, and more recently 15 received once-daily treatment with dose painting. With the exception of Stage I disease (n = 5) and patient preference (n = 1), 69 patients received concurrent and adjuvant platinum-based chemotherapy similar to that in the Intergroup 0099 trial. RESULTS: Patient characteristics: median age 45; 32% Asian; 72% male; 65% World Health Organization III; 6% Stage I, 16% Stage II, 30% Stage III, 47% Stage IV. Median follow-up is 35 months. The 3-year actuarial rate of local control is 91%, and regional control is 93%; freedom from distant metastases, progression-free survival, and overall survival at 3 years are 78%, 67%, and 83%, respectively. There was 100% local control for Stage T1/T2 disease, compared to 83% for T3/T4 disease (p = 0.01). Six patients failed at the primary site, with median time to local tumor progression 16 months; 5 were exclusively within the 70 Gy volume, and 1 was both within and outside the target volume. There is a trend for improved local control with IMRT when compared to local control of 79% for 35 patients treated before 1998 with three-dimensional planning and chemotherapy (p = 0.11). Six months posttherapy, 21%, 13%, 15%, and 0% of patients with follow-up audiograms (n = 24 patients) had Grade 1, 2, 3, and 4 sensorineural hearing loss, respectively. For patients with >1 year follow-up (n = 59), rates of long-term xerostomia were as follows: 26% none, 42% Grade 1, 32% Grade 2, and zero Grade 3. CONCLUSIONS: The pattern of primary site failure within the target volume suggests locally advanced T stage disease may require a higher biologic dose to gross tumor. Rates of severe (Grade 3-4) ototoxicity and xerostomia are low with IMRT as a result of normal-tissue protection. Distant metastases are now the dominant form of failure, emphasizing the need for improved systemic therapy.