Clinical review of the Japanese experience with boron neutron capture therapy and a proposed strategy using epithermal neutron beams

Summary Our concept of boron neutron capture therapy (BNCT) is selective destruction of tumor cells using the heavy-charged particles yielded through¹⁰B(n, α)⁷Li reactions. To design a new protocol that employs epithermal neutron beams in the treatment of glioma patients, we examined the relationship between the radiation dose, histological tumor grade, and clinical outcome. Since 1968, 183 patients with different kinds of brain tumors were treated by BNCT; for this retrospective study, we selected 105 patients with glial tumors who were treated in Japan between 1978 and 1997. In the analysis of side effects due to radiation, we included all the 159 patients treated between 1977 and 2001. With respect to the radiation dose (i.e. physical dose of boron n-alpha reaction), the new protocol prescribes a minimum tumor volume dose of 15 Gy or, alternatively, a minimum target volume dose of 18 Gy. The maximum vascular dose should not exceed 15 Gy (physical dose of boron n-alpha reaction) and the total amount of gamma rays should remain below 10 Gy, including core gamma rays from the reactor and capture gamma in brain tissue. The outcomes for 10 patients who were treated by the new protocol using a new mode composed of thermal and epithermal neutrons are reported.     

Boron neutron capture therapy of brain tumors: clinical trials at the finnish facility using boronophenylalanine

Summary Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400 mg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61 Gy (W), and the average normal brain dose from 3 to 6 Gy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50–60 Gy, were treated with BPA-based BNCT using the BPA dosage of 290 mg/kg. The average planning target dose in these patients was 25–29 Gy (W), and the average whole brain dose 2–3 Gy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photo radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.     

鼻咽癌调强放疗初步结果

目的:探讨鼻咽癌三维适形调强放射治疗(intensity-modulatedradiotherapy,IMRT)的初步疗效。方法:对91例经病理确诊的鼻咽低分化鳞癌患者进行调强放疗。处方剂量分别为GTV(鼻咽部和颈部淋巴结肿瘤靶区)66~70Gy,CTV1(临床靶区)60~62Gy,CTV2和CTVn(颈部淋巴结区域)54~56Gy。11例患者IMRT结束后有局部残留,1例采用IMRT追量照射10Gy/4次,其余给予鼻咽腔内后装追量照射9~15Gy/3~5次。分析疗效及放射治疗毒性。结果:中位随访时间12个月,1和2年生存率为97·1%和97·1%,局控率为97·1%和92·5%。急性放射反应多为Ⅰ度和Ⅱ度以口干和放射性口腔炎为主,分别占72·5%和58·2%。远期放射反应表现为不同程度的口干和听力下降,占患者的39·6%和17·6%。GTV、CTV1及CTV2的平均剂量分别为70·6、67·9和65·0Gy;5%体积的正常器官受照射剂量的平均值为:脑干41·4Gy,脊髓35·4Gy,左腮腺46·5Gy,右腮腺51·8Gy。结论:调强放疗能使得鼻咽癌各靶区得到很好的剂量分布,提高了初治鼻咽癌的局部控制率,明显减轻了急性放射反应。鼻咽癌IMRT处方剂量70Gy以上,CTV2预防照射的范围有待于进一步探讨。     

49例复发鼻咽癌的调强适形放射治疗

目的 评价调强适形放射治疗(IMRT)对复发性鼻咽癌的疗效、放射反应以及对肿瘤的控制。方法 49例鼻咽局部复发的鼻咽癌患者(KPS≥80)均采用全程IMRT,其中伴有颈淋巴结转移的3例患者(N12例,N3l例)在IMRT后,给予PDD 5-Fu方案5～6个疗程化疗。结果 治疗计划结果显示,覆盖鼻咽GTV D95的平均剂量为68．09Gy,GTV V95的平均体积为98．46％,靶区内GTV、CTV1和CTV2的平均剂量分别为71．40Gy、63．63Gy和59．81Gy。49例患者的中位随访时间为9个月(3～16个月)。局部无进展生存率100％,IMRT结束时有3例(6．1％)出现局部残留,14例(28．6％)出现鼻咽腔黏膜坏死。结论 IMRT能有利覆盖肿瘤靶区而使邻近敏感器官获得有效分隔,对复发性鼻咽癌的再程放疗不失为一种有效方法。值得注意的是高剂量的鼻咽局部IMRT治疗对于复发性鼻咽癌容易导致鼻咽黏膜坏死,故应适当减少GTV的处方剂量以60～65Gv为宜。     

初治鼻咽癌调强放疗布野及联合化疗的临床研究

[目的]研究鼻咽癌调强放射治疗(IMRT)的投照方式、近期临床疗效,以及单纯放疗和放、化疗结合的耐受性。[方法]2003年12月￣2005年12月157例初治鼻咽癌患者鼻咽和全颈及锁骨上全程实施前7野IMRT。鼻咽大体肿瘤体积(GTV1)、颈部大体肿瘤体积(GTV2)、临床靶体积1(CTV1)和临床靶体积2(CTV2)处方剂量分别为70Gy、66Gy、60Gy、50Gy,共32分次。88例患者行联合化疗。采用Kaplan-Meier法进行生存分析,RTOG标准评价急性反应和晚期损伤。[结果]治疗计划结果显示,靶区内GTV1、GTV2、CTV1和CTV2的平均剂量分别为70.5Gy、67.0Gy、60.1Gy和51.2Gy。中位随访时间16个月,1、2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97.4%、94.9%和93.6%、89.4%及96.4%、92.7%。放化综合治疗组的口咽、黏膜反应及血液系统毒性明显高于单纯放疗组。患者近期毒副反应均可以耐受,口干症状随着治疗后时间的延长逐渐减轻。[结论]IMRT使靶体积照射剂量提高,而周围器官受照剂量降低,对初治鼻咽癌可获得理想的局部区域控制,放化综合治疗对控制远处转移有一定价值。     

中晚期非小细胞肺癌放疗临床靶区设置的必要性

目的:探讨中晚期非小细胞肺癌放疗时临床靶区设置的必要性。方法:2006年－2012年福建省肿瘤医院177例经病理组织学和(或)细胞学确诊的中晚期非小细胞肺癌患者接受三维适形放疗或者调强放疗,根据靶区勾画原则分为不勾画肺部肿瘤临床靶区组:勾画肿瘤靶区（GTV）和计划靶区（PTV）,勾画肺部肿瘤临床靶区组:勾画肿瘤靶区（GTV）、临床靶区（CTV）和计划靶区（PTV）。两组肺部病灶分割剂量200~220 cGy/次,5次/周,肺部病灶放疗剂量 DT 5 600~6 600 cGy。两组资料经统计学分析具有可比性。结果:不勾画肺部肿瘤临床靶区组和勾画肺部肿瘤临床靶区组相比,肺部肿瘤平均剂量分别为59.6 Gy、60.7 Gy。两组近期总有效率（CR+PR）分别为76.30%、83.33%（P=0.230）。1、2、3年无进展生存率分别为52.98%、35.35%、24.3%和38.95%、24.33%、11.5%（P=0.360）。1、2、3年总生存率分别为69.9%、45.3%、30.8%和62.18%、37.59%、26.58%（P=0.573）。1、2、3年远处转移率分别为61.07%、40.27%、30.4%和43.55%、32.03%、27.56%（P=0.481）。两组复发率分别为38.52%、59.52%,均为野内复发。两组放射性肺炎发生率分别为16.30%、33.33%（P=0.017）,放射性食管炎发生率分别为18.52%、21.43%（P=0.414）,骨髓抑制发生率分别为38.52%、33.33%（P=0.338）,两组均未出现3级以上放射性肺炎。结论:不勾画肺部肿瘤临床靶区使肺部放疗区域减少,治疗后并不减少局部肿瘤的无进展生存和总生存率,但明显减少放射性肺炎的发生率。     

肿瘤体积和放疗剂量对体部γ刀治疗肝细胞肝癌的预后影响

目的 探索GTV和放疗剂量对体部γ刀治疗肝细胞肝癌的预后影响。 方法 回顾分析2012—2015年间 69例体部γ刀治疗肝细胞肝癌患者临床资料。采用50%或60%等剂量曲线覆盖计划靶区,单次 4~5 Gy,边缘总剂量 36~50 Gy (中位数45 Gy)。观察其近期疗效、总生存期及不良反应。采用ROC曲线确定肿瘤体积最佳界值。采用Kaplan-Meier法计算生存率,Logrank检验和单因素分析,Cox模型多因素分析。 结果 69例患者放疗近期总有效率为67%。1、2年生存率分别为62%、40%,中位生存期18.6个月。多因素分析显示GTV<93 cm³(P=0.013)及放疗近期有效(P=0.000)是影响生存的因素。GTV<93 cm³时患者≥45 Gy亚组预后明显好于<45 Gy亚组(P=0.019),而GTV≥93 cm³组患者中剂量大小对生存期无明显影响(P=0.665)。 结论 肿瘤体积是影响局部晚期肝癌患者生存的独立预后因素。小体积肿瘤行大剂量放疗患者生存获益。对肿瘤体积较大患者不宜强行追求高剂量照射。     

鼻咽癌调强放射治疗的剂量学特点

[目的]分析鼻咽癌调强放疗各个靶区和周围正常器官的剂量学特点.[方法]2004年7月至10月入院的10例初治鼻咽癌调强放疗病人,用前7野方案,每野的照射范围从颅底到锁骨上淋巴预防区.剂量处方是:GTV1为2.18Gy/次,32次,GTV2为2.03Gy/次,32次,CTV1为1.88Gy/次,32次,CTV2为1.80Gy/次,28次.研究GTV的最大、最小和平均剂量,CTV的最小剂量,脊髓、脑干和晶状体的最大剂量,腮腺的50%体积受照剂量.[结果]10例病人GTV1的最大、最小和平均剂量(均值)分别是72.01Gy、68.65Gy、70.48Gy,GTV2的最大、最小和平均剂量(均值)分别是68.66y、65.50Gy、66.98Gy,CTV1的最小剂量为60.10Gy,CTV2的最小剂量为51.18Gy,脊髓、脑干和晶体状的最大剂量分别为44.7Gy、51.7Gy和6.8Gy,高剂量侧和低剂量侧,腮腺的50%体积的受照剂量分别为44.39Gy和39.36Gy.[结论]调强放疗可以使各个靶区得到足够的、均匀的剂量分布,周围的正常组织受到比较好的保护,腮腺50%体积受照剂量控制在40Gy～45Gy,显示已有较好的保护作用.     

Treatment planning and dosimetry for the Harvard-MIT Phase I clinical trial of cranial neutron capture therapy

: A Phase I trial of cranial neutron capture therapy (NCT) was conducted at Harvard-MIT. The trial was designed to determine maximum tolerated NCT radiation dose to normal brain.

: Twenty-two patients with brain tumors were treated by infusion of boronophenylalanine-fructose (BPA-f) followed by exposure to epithermal neutrons. The study began with a prescribed biologically weighted dose of 8.8 RBE (relative biologic effectiveness) Gy, escalated in compounding 10% increments, and ended at 14.2 RBE Gy. BPA-f was infused at a dose 250–350 mg/kg body weight. Treatments were planned using MacNCTPlan and MCNP 4B. Irradiations were delivered as one, two, or three fields in one or two fractions.

: Peak biologically weighted normal tissue dose ranged from 8.7 to 16.4 RBE Gy. The average dose to brain ranged from 2.7 to 7.4 RBE Gy. Average tumor dose was estimated to range from 14.5 to 43.9 RBE Gy, with a mean of 25.7 RBE Gy.

: We have demonstrated that BPA-f-mediated NCT can be precisely planned and delivered in a carefully controlled manner. Subsequent clinical trials of boron neutron capture therapy at Harvard and MIT will be initiated with a new high-intensity, high-quality epithermal neutron beam.     

Comparison with dose-volume histograms of two conformal irradiation techniques used for the treatment of T2N0M0 nasopharyngeal cancer, one with association of photons and protons and another with photons alone]

Purpose- There is a relationship between the local control rate of the nasopharyngeal cancer and the total dose delivered within the tumoral volume. In contrast, the relation between the dose and the irradiated volume and the risk of complication is not clearly defined. That is why, in patients presenting with a locally advanced nasopharyngeal cancer, we compared the dose-volume distribution of irradiated tissues, obtained from two 3D conformal irradiation techniques.Patients and methods- Between January 2000 and June 2001, 5 patients, 3 males and 2 females, with a median age of 32 years and presenting with a T4N0M0 nasopharyngeal cancer received a chemoradiotherapy. Radiotherapy combined photons and protons beams and the platin-based chemotherapy was delivered in three intravenous injections at d1, 22, 43 of the irradiation. To calculate the dosimetry, a CT scan and a MRI were performed in all the patients. The gross tumor volume (GTV) was delineated from the imagery, three clinical tumor volumes were defined, the CTV1 was the GTV and the whole nasopharynx, the CTV2 was the CTV plus a 10 mm-margin and the CTV3 was the CTV2 and the nodes areas (cervical and subclavicular). Prophylactic dose within node areas was 44 Gy. Prescribed doses within CTV2 and GTV or CTV1 were 54 Gy/CGE (Cobalt Gy Equivalent, for an EBR = 1,1) and 70 Gy/CGE, respectively. Irradiation was delivered with fractions of 1.8 or 2.0 Gy/CGE, with 44 Gy or 54 Gy by photons and with 16 or 26 CGE by protons. According to dose-volume histograms obtained from the dosimetry planning by protons and photons and from the theoretical dosimetry by photons lonely, for the different volumes of interest, GTV, CTV2, and organs at risk (optic nerves, chiasm, internal ears, brainstem, temporal lobes), we compared the averages of the maximum, minimum and mean doses and the averages of the volumes of organs of interest encompassed by different isodoses.Results- Calculated averages of minimum, maximum and mean doses delivered within GTV were superior for the treatment with combined photons and protons than with photons alone. The average GTV encompassed by the 70 Gy/CGE isodose was larger by 65% with the association compared to photons alone. The conformation ratio (tissue volume encompassed by the 95% isodose/GTV encompassed by the 95% isodose) was 3.1 with the association compared to 5.7 with photons alone. For the CTV2, there were no differences in different criteria according to the both irradiation techniques. For the critical, radiosensitive organs, the comparison of the majority of the criteria was in favour of the association of protons and photons. Overall, 78% of the criteria were in favour of the association.Conclusion- For locally advanced nasopharyngeal cancer without clinical adenopathy, irradiation by photons and protons increases the tumor volume irradiated at the prescribed dose and decreases the volume or critical organs irradiated and the total dose delivered within them.     

Boron neutron capture therapy: cellular targeting of high linear energy transfer radiation

Boron neutron capture therapy (BNCT) is based on the preferential targeting of tumor cells with (10)B and subsequent activation with thermal neutrons to produce a highly localized radiation. In theory, it is possible to selectively irradiate a tumor and the associated infiltrating tumor cells with large single doses of high-LET radiation while sparing the adjacent normal tissues. The mixture of high- and low-LET dose components created in tissue during neutron irradiation complicates the radiobiology of BNCT. Much of the complexity has been unravelled through a combination of preclinical experimentation and clinical dose escalation experience. Over 350 patients have been treated in a number of different facilities worldwide. The accumulated clinical experience has demonstrated that BNCT can be delivered safely but is still defining the limits of normal brain tolerance. Several independent BNCT clinical protocols have demonstrated that BNCT can produce median survivals in patients with glioblastoma that appear to be equivalent to conventional photon therapy. This review describes the individual components and methodologies required for effect BNCT: the boron delivery agents; the analytical techniques; the neutron beams; the dosimetry and radiation biology measurements; and how these components have been integrated into a series of clinical studies. The single greatest weakness of BNCT at the present time is non-uniform delivery of boron into all tumor cells. Future improvements in BNCT effectiveness will come from improved boron delivery agents, improved boron administration protocols, or through combination of BNCT with other modalities.     

Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology.

The second part of the GYN GEC ESTRO working group recommendations is focused on 3D dose-volume parameters for brachytherapy of cervical carcinoma. Methods and parameters have been developed and validated from dosimetric, imaging and clinical experience from different institutions (University of Vienna, IGR Paris, University of Leuven). Cumulative dose volume histograms (DVH) are recommended for evaluation of the complex dose heterogeneity. DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to 90 and 100% of the respective volume: D90, D100. The volume, which is enclosed by 150 or 200% of the prescribed dose (V150, V200), is recommended for overall assessment of high dose volumes. V100 is recommended for quality assessment only within a given treatment schedule. For Organs at Risk (OAR) the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3. Underlying assumptions are: full dose of external beam therapy in the volume of interest, identical location during fractionated brachytherapy, contiguous volumes and contouring of organ walls for >2 cm3. Dose values are reported as absorbed dose and also taking into account different dose rates. The linear-quadratic radiobiological model-equivalent dose (EQD2)-is applied for brachytherapy and is also used for calculating dose from external beam therapy. This formalism allows systematic assessment within one patient, one centre and comparison between different centres with analysis of dose volume relations for GTV, CTV, and OAR. Recommendations for the transition period from traditional to 3D image-based cervix cancer brachytherapy are formulated. Supplementary data (available in the electronic version of this paper) deals with aspects of 3D imaging, radiation physics, radiation biology, dose at reference points and dimensions and volumes for the GTV and CTV (adding to [Haie-Meder C, P?tter R, Van Limbergen E et al. Recommendations from Gynaecological (GYN) GEC ESTRO Working Group (I): concepts and terms in 3D image-based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235-245]). It is expected that the therapeutic ratio including target coverage and sparing of organs at risk can be significantly improved, if radiation dose is prescribed to a 3D image-based CTV taking into account dose volume constraints for OAR. However, prospective use of these recommendations in the clinical context is warranted, to further explore and develop the potential of 3D image-based cervix cancer brachytherapy.     

鼻咽癌缩小临床靶体积调强放疗疗效探讨

目的 探讨鼻咽癌(NPC)缩小临床靶体积(CTV)调强放疗(IMRT)的疗效及毒副反应.方法 2003年8月到2007年3月共380例NPC患者入组研究,其中AJCC分期Ⅰ期1例、Ⅱ期71例、Ⅲ期197例、Ⅳ期111例.高危临床靶体积(CTV1)包括肿瘤靶体积(GTV)及整个鼻咽黏膜,低危临床靶体积(CTV2)包括整个鼻咽腔(包括鼻腔后部5 mm)、上颌窦(后壁前5 mm)、翼腭窝、后组筛窦、咽旁间隙、颅底、斜坡及颈椎前1/3、咽后淋巴引流区(内侧组从颅底至第2颈椎上缘).处方剂量GTV 66.00～69.75 Gy,CTV160.00～66.65 Gy,CTV2或CTVN54.0～55.8 Gy,分割次数均为30～33次.其中308例局部进展患者接受了以铂类为基础的诱导化疗.结果 随访率为100%,随访满3年者145例.3年局部控制率、区域控制率、无远处转移生存率、无瘤生存率及总生存率分别为94.9%、97.4%、86.2%、80.9%和89.0%.多因素分析表明N分期是影响无远处转移生存率(x2=20.80,P=0.001)的预后因素,N分期(x2=18.30,P=0.003)及年龄(x2=7.31,P=0.004)是影响总生存率的独立预后因素.5.6%患者放疗后2年仍存在2级口干,未观察到4级远期副反应.4.2%、2.6%和12.1%患者分别出现局部、区域复发及远处转移.结论 采用缩小CTV2IMRT方法治疗NPC可获得较好的局部区域控制率及总生存率,急慢性副反应可接受.     

Boron neutron capture therapy for glioblastoma multiforme: clinical studies in Sweden

Summary A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radiobiological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol,p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15–32 μg/g) at the time of irradiation (approximately 2–3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0–15.5 Gy(W) and 3.3–6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.     

Clinical Review of the Japanese Experience with Boron Neutron Capture Therapy and A Proposed Strategy Using Epithermal Neutron Beams

Our concept of boron neutron capture therapy (BNCT) is selective destruction of tumor cells using the heavy-charged particles yielded through ¹⁰ B(n, )⁷ Li reactions. To design a new protocol that employs epithermal neutron beams in the treatment of glioma patients, we examined the relationship between the radiation dose, histological tumor grade, and clinical outcome. Since 1968, 183 patients with different kinds of brain tumors were treated by BNCT; for this retrospective study, we selected 105 patients with glial tumors who were treated in Japan between 1978 and 1997. In the analysis of side effects due to radiation, we included all the 159 patients treated between 1977 and 2001.With respect to the radiation dose (i.e. physical dose of boron n-alpha reaction), the new protocol prescribes a minimum tumor volume dose of 15Gy or, alternatively, a minimum target volume dose of 18Gy. The maximum vascular dose should not exceed 15Gy (physical dose of boron n-alpha reaction) and the total amount of gamma rays should remain below 10Gy, including core gamma rays from the reactor and capture gamma in brain tissue.The outcomes for 10 patients who were treated by the new protocol using a new mode composed of thermal and epithermal neutrons are reported.     

局部晚期宫颈癌CT图像引导下192Ir三维腔内后装治疗剂量体积参数与疗效关系

目的 观察CT图像引导下192Ir三维腔内后装治疗的肿瘤靶区及危及器官受照射体积剂量参数与肿瘤局部控制率及晚期副反应之间关系.方法 10例局部晚期宫颈癌患者在完成盆腔外照射40 Gy及同期化疗后开始每周1次的CT图像引导下192Ir三维腔内后装治疗,每次治疗前进行CT扫描定位,勾画肿瘤靶区(GTV、CTV)和危及器官,利用PLATO治疗计划系统进行逆向治疗计划设计及优化,CTV单次处方剂量为6 Gy,治疗5～7次.结果 1年盆腔控制率为90%,1～2级放射性肠炎发生率为50%,无≥3级副反应.90%CTV等效生物剂量(BED)和相当于2 Gy分次的等效剂量(EQD2)分别为(95.50±7.81)Gy和(79.73±6.57)Gy(α/β=10).90%GTV的BED和EQD2分别为(101.86±7.27)Gy和(84.95±6.1)Gy(α/β=10).90%处方剂量对GTV、CTV的覆盖率分别为92%±4%、87%±7%.直肠、乙状结肠2 cm3体积受到的最小照射剂量分别为(74.97±1.64)、(67.93±4.30)Gy(EQD2,α/β=3).与二维治疗计划相比,三维治疗计划在没有改变A点剂量、直肠参考点剂量情况下提高了GTV、CTV的90%体积受照射剂量及90%处方剂量对GTV、CTV的覆盖率.结论 CT图像引导下192Ir三维腔内后装治疗提高了处方剂量对肿瘤靶区的覆盖率,1年盆腔控制率为90%且无严重副反应,远期疗效观察中.

Abstract：

Objective To investigate the correlation between dose volume histogram(DVH)of tumor targets and organs at risk(OAR)at CT-image based 192Ir brachytherapy and effects and complications for patients with locally advanced cervical cancer. Methods Ten patients with FIGO stage ⅢB cervical cancer received CT image-based 192Ir intracavitary brachytherapy after 54 Gy of three-dimentional four-field pelvic external beam radiotherapy and concurrent weekly cisplatin chemotherapy. Before each brachytherapy,CT images were acquired with applicators in place. Gross tumor volume(GTV), clinical target volume (CTV)and OAR were contoured and inverse treatment planning was designed and optimized by using PLATO treatment planning system. Conventional two-dimensional plans were also designed for comparison.The total intracavitary brachytherapy dose was 30 -42 Gy in 5 -7 fractions. The patients were followed, and the local control and complications were analyzed. The biologically equivalent dose(BED)and biologically equivalent dose in 2 Gy fractions(BED2)for GTV, CTV and OAR were calculated. The minimum dose in the most irradiated tissue volume 2 cm3(D2 cm3)adjacent to the applicator of the sigmoid colon, rectum,bladder and small bowel was determined from the DVH. Results The 1-year local pelvic control rate was 90% and grade 1-2 late complication of sigmoid colon and rectum was 50%. No grade 3 or more complications developed. On CT-image based planning, the BED and BED2 to 90% of the CTV(D90)were 95.50 Gy ± 7. 81 Gy and 79. 73 Gy ± 6. 57 Gy. The BED and BED2 to 90% of the GTV(D90)were 101.86 Gy ± 7.27 Gy and 84. 95 Gy ± 6. 1 Gy. The volume enclosed by 90% of prescribed dose(V90)for GTV and CTV were 92% ±4% and 87% ±7% respectively. The D2cm3 for rectum and sigmoid colon were 74. 97 Gy ±1.64 Gy and 67. 93 Gy ± 4. 30 Gy(EQD2, α/β = 3). Comparing with 2D brachytherapy plans , CT - image based planning has improved D90 and V90 for GTV and CTV with similar dose at point A and rectum reference point. Conclusions Computer tomography-image based 192Ir brachytherapy has resulted in the better dose distribution to the tumor targets with excellent tumor control and acceptable toxicity.     

Radiosurgery for brain metastasis: impact of CTV on local control.

PURPOSE: The purpose of the present analysis was to assess whether adding a 1 mm margin to the gross tumour volume (GTV) improves the control rate of brain metastasis treated with radiosurgery (RS). PATIENTS AND METHODS: All the patients had one or two brain metastases, 30 mm or less in diameter, and only one isocentre was used for RS. There were 23 females and 38 males. The median age was 54 years (34-76). The median Karnofsky performance status was 80 (60-100). At the time of RS, 23 patients had no evidence of extracranial disease and 38 had a progressive systemic disease. Thirty-eight patients were treated up-front with only RS. Twenty-three patients were treated for relapse or progression more than 2 months after whole brain radiotherapy. From January 1994 to July 1995, clinical target volume (CTV) was equal to GTV without any margin (33 metastases). From August 1995 to August 2000, CTV was defined as GTV plus a 1 mm margin (45 metastases). A dose of 20Gy was prescribed to the isocentre and 14Gy at the margin of CTV. RESULTS: The median follow-up was 10.5 months (1-45). The mean minimum dose delivered to GTV was 14.6Gy in the group without a margin and 16.8Gy in the group with a 1 mm margin (P<0.0001). The response of 11 metastases was never assessed because patients died before the first follow-up. Ten metastases recurred, eight in the group treated without a margin and two in the group treated with a 1 mm margin (P=0.01). Two-year local control rates were 50.7+/-12.7% and 89.7+/-7.4% (P=0.008), respectively. Univariate analysis showed that the treatment group (P=0.008) and the tumour volume (P=0.009) were prognostic factors for local control. In multivariate analysis, only the treatment group with a 1 mm margin was an independent prognostic factor for local control (P=0.04, RR: 5.8, 95% CI [1.08-31.13]). There were no significant differences, either in overall survival rate or in early and late side effects, between the two groups. CONCLUSION: Adding a 1 mm margin to the GTV in patients treated with RS significantly improves the probability of metastasis control without increasing the side effects.