Optimizing breast cancer treatment efficacy with intensity-modulated radiotherapy

: To present our clinical experience using intensity-modulated radiation therapy (IMRT) to improve dose uniformity and treatment efficacy in patients with early-stage breast cancer treated with breast-conserving therapy.

: A total of 281 patients with Stage 0, I, and II breast cancer treated with breast-conserving therapy received whole breast RT after lumpectomy using our static, multileaf collimator (sMLC) IMRT technique. The technical and practical aspects of implementing this technique on a large scale in the clinic were analyzed. The clinical outcome of patients treated with this technique was also reviewed.

: The median time required for three-dimensional alignment of the tangential fields and dosimetric IMRT planning was 40 and 45 min, respectively. The median number of sMLC segments required per patient to meet the predefined dose-volume constraints was 6 (range 3–12). The median percentage of the treatment given with open fields (no sMLC segments) was 83% (range 38–96%), and the median treatment time was <10 min. The median volume of breast receiving 105% of the prescribed dose was 11% (range 0–67.6%). The median breast volume receiving 110% of the prescribed dose was 0% (range 0–39%), and the median breast volume receiving 115% of the prescribed dose was also 0%. A total of 157 patients (56%) experienced Radiation Therapy Oncology Group Grade 0 or I acute skin toxicity; 102 patients (43%) developed Grade II acute skin toxicity and only 3 (1%) experienced Grade III toxicity. The cosmetic results at 12 months (95 patients analyzable) were rated as excellent/good in 94 patients (99%). No skin telengiectasias, significant fibrosis, or persistent breast pain was noted.

: The use of intensity modulation with our sMLC technique for tangential whole breast RT is an efficient method for achieving a uniform and standardized dose throughout the whole breast. Strict dose-volume constraints can be readily achieved resulting in both uniform coverage of breast tissue and a potential reduction in acute and chronic toxicities. Because the median number of sMLC segments required per patient is only 6, the treatment time is equivalent to conventional wedged-tangent treatment techniques. As a result, widespread implementation of this technology can be achieved with minimal imposition on clinic resources and time constraints.     

左侧乳腺癌放疗相关心脏毒性的危险因素分析

 放射治疗是乳腺癌的重要治疗手段,由于左乳与心脏位置毗邻,设计照射野时常不能完全避开心脏。乳腺癌放射治疗增加了患缺血性心脏病、心包炎和瓣膜病的风险。年轻、高体重指数（body mass index, BMI）、肿瘤位于中央象限和胸骨旁区域与心脏受到高剂量辐射有关。放疗心脏毒性与放疗技术有很大关系,对于左乳切除术后放疗,多野调强适形放疗（IMRT）能够平衡靶区覆盖和正常组织受量,而左乳保乳术后放疗,采用双弧度容积旋转调强（VMAT）较多野IMRT更具优势。相比全乳照射,加速部分乳腺照射能够显著降低心脏剂量;而对于需要照射区域淋巴结的患者,采用容积旋转调强或螺旋断层放疗在减少心脏受量方面则显示出优势。相比自由呼吸,深吸气屏气放疗能够显著减少心脏和冠状动脉左前降支剂量;尤其是对于胸壁+区域淋巴结（包括内如淋巴结）放疗的患者采用深吸气屏气（deep inspiration breath hold, DIBH）放疗获益更多,而对于保乳术后仍为大乳腺的患者,采用俯卧位能减少心脏毒性。另外,左乳放疗期间同步曲妥珠单抗靶向治疗、芳香化酶抑制剂（aromatase inhibitors, AI）会影响心脏事件的发生。基于上述因素,在给左侧乳腺癌患者制定放疗计划时,应结合患者年龄、BMI、原发肿瘤位置、体型、术后乳腺大小、是否需要区域淋巴结照射,根据现有放疗设备,给予最优的放疗方案,同时减少增加心脏毒性的同步治疗,从而最大程度减少治疗导致的心脏不良反应。     

早期乳腺癌保乳术后调强放疗

现行早期乳腺癌保乳术后的常规切线野放射治疗技术存在靶区内剂量不均匀的缺陷.国内外多位研究者将调强放疗(IMRT)应用于保乳术后患者,以期在提高靶区剂量均匀性、降低危及器官受量及改善美容效果方面体现出一定优势.     

Advanced radiation therapy technologies in the treatment of rectal and anal cancer: intensity-modulated photon therapy and proton therapy

Intensity-modulated photon radiation therapy (RT; IMRT) and proton therapy are advanced radiation technologies that permit improved conformation of radiation dose to target structures while limiting irradiation of surrounding normal tissues. Application of these technologies in the treatment of rectal and anal cancer is attractive, based on the potential reduction in radiation treatment toxicities that are frequently incurred in the pelvis and perineum. Furthermore, conformal RT might also allow for dose escalation to target areas, leading to improved tumor control. This review discusses the underlying principles of IMRT. In addition, the rationale and clinical data regarding the efficacy of radiation dose escalation for rectal and anal cancer will be highlighted, as well as tolerance of pelvic organs to RT and chemotherapy. Finally, preliminary results of IMRT in the treatment of lower gastrointestinal tract cancers will be reviewed. The potential and rationale for proton therapy in treatment of these malignancies are also discussed.     

固定铅门调强技术对乳腺癌术后放射治疗计划设计的作用

目的：近年来固定铅门技术在调强治疗计划设计中已经被广泛使用,本文对比固定铅门（ Fixed jaw）和动态铅门（Jaw tracking）两种技术在乳腺癌调强放射治疗计划设计中的优缺点,探讨固定铅门调强放射治疗技术对乳腺癌治疗计划设计的作用。方法：固定铅门技术是在常规调强放射治疗技术的基础上,人为限定铅门和光栅的作用范围,使某些照射野作用于特定的治疗区域,从而期望得到更好的治疗计划方案。本文选取21例以往进行过 Jaw tracking 技术调强放射治疗的病例,应用 Fixed jaw 技术重新进行计划设计。对应用两种技术的调强放射治疗计划靶区的 Dmean ,Dmin ,Dmax 和患侧肺以及心脏的受照剂量进行对比。同时也对靶区的均匀性指数和适形度指数做了对比。结果：在保证靶区处方剂量的前提下,固定铅门技术相比于动态铅门技术可以明显降低肺 V     

同时性双侧乳腺癌保乳术后放疗技术和近期疗效分析

目的 探讨同时性双侧乳腺癌整体等中心切线野混合调强技术的剂量特点及疗效。方法 纳入14例同时性双侧乳腺癌保乳术后双侧全乳±瘤床加量放疗患者。采用等中心切线野混合调强技术进行双乳整体放疗(50Gy分25次或43.5Gy分15次)。分析计划的覆盖度、均匀性及临床近期疗效。结果 全组患者放疗计划总野数为8~11个,其中调强野为4~7个。全乳计划靶区均达95%,平均瘤床覆盖度在X线同步补量组分别为(95.54±1.33)%(左)及(94.19±1.03)%(右),在电子线序贯补量组为(90.25±8.79)%(左)及(85.28±8.35)%(右)。平均双肺V20为(16.69±3.90)%,平均心脏Dmean为5.48Gy。全组3例出现2级急性皮肤反应,无≥2级的放射性肺炎发生。中位随访至30.1个月时,11例美容效果为优,无一复发。结论 双乳腺癌保乳术后采用整体等中心切线野混合调强技术安全可靠。     

Intensity-modulated radiation therapy for the treatment of anal cancer

PURPOSE: The aim of this study was to assess whether intensity-modulated radiation therapy (RT; IMRT) can reduce dose to normal tissues (organs at risk) while maintaining equivalent target coverage. PATIENTS AND METHODS: A 9-field, non-coplanar, 1-cm beamlet IMRT plan was designed for 9 patients who were previously treated for anal cancer with conventional field arrangements. Clinical target volumes and organs at risk (OARs) were defined. Target coverage was assigned highest priority for optimization, followed sequentially by organ at risk. The genitalia and perineal skin were the highest priority OARs. Lexicographic ordering-based IMRT optimization was used to generate a conformal plan, which was compared with the conventional, previously delivered RT plan. RESULTS: The IMRT and conventional RT plan achieved homogeneous dose coverage of all target volumes. Intensity-modulated RT produced highly conformal dose distributions compared with conventional techniques, with avoidance of critical normal structures. Statistically significant reductions in mean doses to the perineal skin and to the genitalia were seen with IMRT, with only a modest increase in mean dose to the bony pelvis. CONCLUSION: Intensity-modulated RT, with lexicographic ordering, allows for substantial reduction of dose to OARs while maintaining adequate target coverage. These encouraging findings might translate into reductions of treatment-related toxicity, gains in local control, or improvements in quality of life.     

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.     

New tools in adjuvant breast cancer radiotherapy

During the last century management of breast cancer became increasingly less aggressive for small tumors. Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery (BCS) followed by adjuvant radiation therapy (RT). BCS plus adjuvant RT +/- systemic therapy has become the standard of care for women with early breast cancer. Advances in modern RT technology allowed significant increase in high precision of target definition. Intensity modulated radiation therapy (IMRT) and gating, under investigation in miscellaneous cancers, are also in development for breast-cancer patients. These techniques decrease radiation toxicities and could be useful in the setting of concurrent use of RT and new systemic therapies such as trastuzumab. Another advance in RT is the development of accelerated partial breast irradiation (APBI) as a new concept in the adjuvant setting for early-stage breast cancer. Intraoperative RT (IORT), immediate postoperative RT (interstitial brachytherapy or Mammosite device implantation) and delayed postoperative RT (external beam of photons or protons with 3D conformation) are under investigation. In this review, the role of modern whole breast irradiation is discussed, the rational of partial breast irradiation is argued and the different techniques are detailed.     

Potential advantages of intensity-modulated radiation therapy in gynecologic malignancies

Radiation therapy (RT) plays a critical role in the management of gynecologic malignancies. Conventional RT may treat a large amount of normal tissue, which results in increased toxicities and a limitation on total dose. Intensity-modulated radiation therapy (IMRT) helps reduce the dose to normal tissue while delivering a higher dose to the tissues with microscopic or gross disease. This may have a potential benefit in the treatment of gynecologic malignancies especially in difficult cases such as grossly positive nodes, recurrent disease, and vulvar cancer. However, there is very little clinical data and very little experience with the use of IMRT in gynecologic malignancies. Therefore, before complete acceptance of IMRT in the treatment of gynecologic malignancies, large multicenter trials are needed to help develop guidelines and standards.     

Cardiac-Sparing Whole Lung Intensity Modulated Radiation Therapy in Children With Wilms Tumor: Final Report on Technique and Abdominal Field Matching to Maximize Normal Tissue Protection

Purpose

Cardiac-sparing whole lung intensity modulated radiation therapy (WL IMRT) has been shown to improve cardiac protection and lung volume dose coverage compared with standard anteroposterior techniques. This dosimetry study had 2 aims: To determine the dosimetric advantages of a modified WL IMRT (M-WL IMRT) technique, designed to reduce radiation exposure to the thyroid gland and breast tissues, compared with standard WL IMRT (S-WL IMRT) and to determine the dosimetric advantages of M-WL IMRT and dosimetrically matched abdomen and flank radiation therapy (RT) fields designed to reduce normal tissue exposure compared with standard field matching techniques.

乳腺癌保乳术+化疗后动态调强放疗的临床观察

目的 观察乳腺癌保乳术+化疗后动态调强放疗的疗效和美容效果.方法 117例乳腺癌患者保乳术后先行4～6周期化疗再三维适形(6例)和动态调强放疗(111例).化疗分别采用CAF(环磷酰胺+多柔比星+氟尿嘧啶)、AC(多柔比星+环磷酰胺)、TA(紫杉醇+多柔比星)、NE(长春瑞滨+表阿霉素)、TX(紫杉醇+卡培他滨)方案.放疗采用6 MV-X线全乳腺调强放疗50Gy,瘤床电子线外照射加量10 Gy;其中68例患者锁骨上预防性照射50 Gy,42例肿块位于内侧象限的同时照射内乳淋巴引流区,锁骨上区、内乳区及胸壁均包在一个靶区里.雌、孕激素受体阳性加用内分泌治疗.治疗结束后6～12个月由2位医师评分评价美容效果.结果 随访至2009年9月,随访率为94.0%,随访满3、5年者分别为114、91例.全组3生存率为99.1%,5年生存率为96%,5年无瘤生存率为88%,局部复发率为3.6%,美容效果满意者为100%.放疗中及放疗结束后未出现明显放射性心肺等重要脏器损伤.结论 乳腺保乳术+化疗后胸壁动态调强放疗使靶区得到更均匀照射,有望提高局部控制率和生存率并降低正常组织并发症、肿瘤复发率.     

Simultaneous integrated boost for breast cancer using IMRT: a radiobiological and treatment planning study

PURPOSE: The purpose of this work is to explore the possibility of using intensity-modulated radiation therapy (IMRT) to deliver the boost dose to the tumor bed simultaneously with the whole-breast IMRT to reduce the radiation treatment time by 1-2 weeks. METHODS AND MATERIALS: The biologically effective dose (BED) for different treatments was calculated using the linear-quadratic (LQ) model with parameters previously derived for breast cancer from clinical data (alpha/beta = 10Gy, alpha = 0.3Gy(-1)). A potential doubling time of 15 days (from in vitro measurements) for breast cancer and a generic alpha/beta ratio of 3 Gy for normal tissues were used. A series of regimens that use IMRT as initial treatment and an IMRT simultaneous integrated boost (SIB) were derived using biologic equivalence to conventional schedules. Possible treatment plans with IMRT SIB to the tumor bed were generated for 2 selected breast patients, 1 with a shallow tumor and 1 with a deep-seated tumor. Plans with a simultaneous integrated electron boost were also generated for comparison. Dosimetric merits of these plans were evaluated based on dose volume histograms. RESULTS: A commonly used conventional treatment of 45 Gy (1.8 Gy x 25) to the whole breast and then a boost of 20 Gy (2 Gy x 10) is biologically equivalent to an alternative plan of 1.8 Gy x 25 to the whole breast with a 2.4 Gy x 25 SIB to the tumor bed. The new regime reduces treatment time from 7 to 5 weeks. For the patient with a deep-seated tumor, the IMRT plans reduce the volume of the breast that receives high doses (compared with the conventional photon boost plan) and provides good coverage of the target volumes. CONCLUSION: It is biologically and dosimetrically feasible to reduce the overall treatment time for breast radiotherapy by using an IMRT simultaneous integrated boost. For selected patient groups, IMRT plans with a new regimen can be equal to or better than conventional plans.     

Skin Toxicity in Early Breast Cancer Patients Treated with Field-In-Field Breast Intensity-Modulated Radiotherapy versus Helical Inverse Breast Intensity-Modulated Radiotherapy: Results of a Phase III Randomised Controlled Trial

AimsSkin toxicity is a common adverse effect of breast radiotherapy. We investigated whether inverse-planned intensity-modulated radiotherapy (IMRT) would reduce the incidence of skin toxicity compared with forward field-in-field breast IMRT (FiF-IMRT) in early stage breast cancer.Materials and methodsThis phase III randomised controlled trial compared whole-breast irradiation with either FiF-IMRT or helical tomotherapy IMRT (HT-IMRT), with skin toxicity as the primary end point. Patients received 50 Gy in 25 fractions and were assessed to compare skin toxicity between treatment arms.ResultsIn total, 177 patients were available for assessment and the median follow-up was 73.1 months. Inverse IMRT achieved more homogeneous coverage than FiF-IMRT; erythema and moist desquamation were higher with FiF-IMRT compared with HT-IMRT (61% versus 34%; P < 0.001; 33% versus 11%; P < 0.001, respectively). Multivariate analysis showed large breast volume, FiF-IMRT and chemotherapy were independent factors associated with worse acute toxicity. There was no difference between treatment arms in the incidence of late toxicities. The 5-year recurrence-free survival was 96.3% for both FiF-IMRT and HT-IMRT and the 5-year overall survival was 96.3% for FiF-IMRT and 97.4% for HT-IMRT.ConclusionsOur study showed significant reduction in acute skin toxicity using HT-IMRT compared with FiF-IMRT, without significant reduction in late skin toxicities. On the basis of these findings, inverse-planned IMRT could be used in routine practice for whole-breast irradiation with careful plan optimisation to achieve the required dose constraints for organs at risk.     

Innovations en radiothérapie

Radiotherapy is a major treatment for cancer curability. During recent years, radiotherapy has gained in precision and reproducibility using major technological advances. Three-dimensional conformal radiotherapy has been implemented into routine practice with the delineation of tumor volumes and organs at risk and the use of dosimetry (integrating dose constraints and dose-volume histograms). Intensity-modulated radiation therapy (IMRT) can ??sculpt?? the dose around treatment volumes to spare normal tissues more efficiently. Image-guided radiation therapy is now widely used to control the position of the target during a treatment course. Dynamic arctherapy is a way to optimize IMRT using arctherapy, an old concept that makes IMRT delivery quicker and accessible for a larger patient load. Concepts in radiotherapy are strong and will be deployed on all radiotherapy units. Radiation oncology is probably only at its dawn. These innovations open a promising future for improvements in the cure of cancer.