Intensity modulated radiotherapy (IMRT) decreases treatment-related morbidity and potentially enhances tumor control

Intensity modulated radiation therapy (IMRT), a new form of three-dimensional conformal radiation therapy (3DCRT), optimizes the concept of computer-controlled radiation deposition in tumor (target) while sparing adjacent normal structures. A retrospective review was done on the initial 185 patients with tumors in different sites including prostate cancer, head and neck cancer, pediatric tumors, adult brain tumors, and previously irradiated recurrent tumors treated with IMRT.

Preliminary findings indicate that IMRT is a new clinically feasible tool in radiation oncology. Treatment-related morbidity profile was favorable. Tumor response, local control, and the ability to palliate previously irradiated patients are encouraging. Intensity modulated radiation therapy will allow dose escalation, leading to better tumor control.     

Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons

BACKGROUND: Over 85% of pediatric orbital rhabdomyosarcoma (RMS) are cured with combined chemotherapy and radiation. However, the late effects of photon radiation compromise function and cosmetic outcome. Proton radiation can provide excellent tumor dose distributions while sparing normal tissues better than photon irradiation. METHODS AND MATERIALS: Conformal 3D photon and proton radiotherapy plans were generated for children treated with proton irradiation for orbital RMS at Massachusetts General Hospital. Dose-volume histograms (90%, 50%, 10%) were generated and compared for important orbital and central nervous system structures. Average percentages of total dose prescribed were calculated based on the 3 dose-volume histogram levels for normal orbital structures for both the proton and photon plans. The percent of normal tissue spared by using protons was calculated. RESULTS: Seven children were treated for orbital rhabdomyosarcoma with proton irradiation and standard chemotherapy. The median follow-up is 6.3 years (range, 3.5-9.7 years). Local and distant controls compare favorably to those in other published accounts. There was an advantage in limiting the dose to the brain, pituitary, hypothalamus, temporal lobes, and ipsilateral and contralateral orbital structures. Tumor size and location affect the degree of sparing of normal structures. CONCLUSIONS: Fractionated proton radiotherapy is superior to 3D conformal photon radiation in the treatment of orbital RMS. Proton therapy maintains excellent tumor coverage while reducing the radiation dose to adjacent normal structures. Proton radiation therapy minimizes long-term side effects.     

Technology insight: Proton beam radiotherapy for treatment in pediatric brain tumors

Tumors of the central nervous system are the most common solid tumor in childhood. Treatment options for childhood brain tumors include radiation therapy, surgery and chemotherapy, often given in combination. Radiation therapy regularly has a pivotal role in treatment, and technological advancements during the past quarter of a century have dramatically improved the ability to deliver radiation in a more focused manner. Improvements in imaging and computing ability led to better targeting of tumor tissue using conventional X-ray therapy. These advances have been harnessed for proton radiation therapy. Proton radiotherapy has special physical characteristics that allow normal tissues to be spared better than even the most conformal photon radiation, and it will reduce the complications from treatment. This review discusses the characteristics of proton radiation, and describes examples of pediatric brain tumor patients who would benefit most from this form of treatment.     

Advanced-technology radiation therapy for bone sarcomas.

BACKGROUND: Bone sarcomas are rare primary tumors. Radiation therapy (RT) can be useful in securing local control in cases where negative surgical margins cannot be obtained or where tumors are not resected. Recent technical advances in RT offer the opportunity to deliver radiation to these tumors with higher precision, thus allowing higher doses to the tumor target with lower doses to critical normal tissues, which can improve local tumor control and/or reduce treatment-related morbidity. METHODS: The authors conducted a survey of recent technical developments that have been applied to the RT for bone sarcomas. RESULTS: RT techniques that show promise include intensity-modulated photon radiation therapy, 3-D conformal proton RT, intensity-modulated proton RT, heavy charged-particle RT, intraoperative RT, and brachytherapy. All of these techniques permit the delivery of higher radiation doses to the target and less dose to normal tissue than had been possible with conventional 3-D conformal radiation techniques. Protons deliver substantially less dose to normal tissues than photons. CONCLUSIONS: Data from clinical studies using these advanced radiation techniques suggest that they can improve the therapeutic ratio (the ratio of local control efficacy to the risk of complications). This is expected to improve the treatment outcome for these challenging tumors.     

Radiation Therapy for Pediatric Brain Tumors using Robotic Radiation Delivery System and Intensity Modulated Proton Therapy

PurposeThis study recruited 2 centers with expertise in treating pediatric brain tumors with robotic radiation delivery system photon therapy and proton therapy, respectively, to study the plan quality and dose deposition characteristics of robotic radiation delivery system photon therapy and intensity modulated proton therapy (IMPT) plans.Methods and MaterialsA total of 18 patients clinically treated with the robotic radiation delivery system were planned with IMPT. Cases were planned per the standard of care of each institution but respected the same planning objectives. The comparison included 3 aspects: plan quality, dose fall-off characteristics around the target volume, and the volume of the high-, intermediate-, and low-dose baths.ResultsAll robotic radiation delivery system and IMPT plans met the planning objectives. However, IMPT significantly reduced the maximum dose to organs at risk away from the planning target volume (PTV), such as the cochlea and eye (P < .05), and the mean dose to the normal brain (P < .05). No statistically significant difference was observed in the maximum dose to the optical pathway and brain stem. Robotic radiation delivery system plans demonstrated a sharper dose fall-off within 5 mm around the PTV (P < .05), whereas IMPT significantly lowered the dose to the normal tissue beyond 10 mm from the PTV (P < .05). The robotic radiation delivery system offers a smaller high-dose bath whereas IMPT offers a smaller low-dose bath (P < .05). However, the difference in intermediate dose is not statistically significant.ConclusionsIn general, robotic radiation delivery system plans exhibit reduced high-dose exposure to normal tissue, and IMPT plans have considerably smaller volumes of low-dose exposure with differences in medium-range dose baths increasingly favoring protons as tumor size increases.     

Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma

PURPOSE: Model the effects of radiation dosimetry on IQ among pediatric patients with central nervous system (CNS) tumors. METHODS AND MATERIALS: Pediatric patients with CNS embryonal tumors (n = 39) were prospectively evaluated with serial cognitive testing, before and after treatment with postoperative, risk-adapted craniospinal irradiation (CSI) and conformal primary-site irradiation, followed by chemotherapy. Differential dose-volume data for 5 brain volumes (total brain, supratentorial brain, infratentorial brain, and left and right temporal lobes) were correlated with IQ after surgery and at follow-up by use of linear regression. RESULTS: When the dose distribution was partitioned into 2 levels, both had a significantly negative effect on longitudinal IQ across all 5 brain volumes. When the dose distribution was partitioned into 3 levels (low, medium, and high), exposure to the supratentorial brain appeared to have the most significant impact. For most models, each Gy of exposure had a similar effect on IQ decline, regardless of dose level. CONCLUSIONS: Our results suggest that radiation dosimetry data from 5 brain volumes can be used to predict decline in longitudinal IQ. Despite measures to reduce radiation dose and treatment volume, the volume that receives the highest dose continues to have the greatest effect, which supports current volume-reduction efforts.     

调强放射治疗计划

调强放射治疗（IMRT）作为一种新近发展起来的先进放射治疗技术。在一些发达国家已经应用于临床,其优势在于肿瘤靶区三维剂量分布的适形程度及其均匀性较标准的适形放疗更好,从而在减少或不增加正常组受高剂量照射的前提下增加肿瘤组织的受照剂量,这样就可以提高肿瘤的局部控制率,降低正常组织并发症的发生率,本文对调强放疗的计划过程、剂量计算及优化方式等进行了综述。     

Uncertainties in physical and biological targeting with radiation therapy

Advances in radiation therapy over the past decade have resulted from increased accuracy of imaging and highly conformal three dimensional treatment planning and delivery of radiation therapy. Three-dimensional conformal radiation therapy (3D CRT) with higher doses than previously considered tolerable is now standard for many types of cancer. Intensity modulated radiation therapy (IMRT) with x-rays, proton beam treatments and intensity modulated proton therapy (IMPT) are major areas of research. Tumor motion between and even during radiation treatments represents a major uncertainty. Tumor heterogeneity results in additional uncertainties affecting tumor control with radiation therapy. Imaging the heterogeneous targets within tumors offers new opportunities for tumor delineation. Molecular therapeutic agents enhance the effects of ionizing radiations in murine systems. Clinical trials combining molecular targeting agents with conformal radiation therapy are being initiated.     

Conformal Therapy for Pediatric Sarcomas

For decades, pediatric oncology has lead the field in the implementation of combined modality therapy and has tested indications for radiation therapy in this patient population. More recently, adult experiences with conformal methods of external beam irradiation and brachytherapy have refined radiation therapy as modality and increased its attractiveness as a means to achieve local control. These refinements come at a time when the current rates of local failure for advanced stage patients with pediatric solid tumors are significant enough to warrant a reexamination of the accepted indications for radiation therapy and its sequencing and dose. Conformal methods of radiation therapy, including brachytherapy, will facilitate efforts to improve local control. These methods have a special role in the pediatric patient where the potential for dose escalation, function preservation, and decreased toxicity can be used to the benefit of these patients, making the majority of them likely to be long-term survivors.     

Organ-sparing radiation therapy for head and neck cancer

To improve locoregional tumor control and survival in patients with locally advanced head and neck cancer (HNC), therapy is intensified using altered fractionation radiation therapy or concomitant chemotherapy. However, intensification of therapy has been associated with increased acute and late toxic effects. The application of advanced radiation techniques, such as 3D conformal radiation therapy and intensity-modulated radiation therapy, is expected to improve the therapeutic index of radiation therapy for HNC by limiting the dose to critical organs and possibly increasing locoregional tumor control. To date, Review articles have covered the prevention and treatment of radiation-induced xerostomia and dysphagia, but few articles have discussed the prevention of hearing loss, brain necrosis, cranial nerve palsy and osteoradionecrosis of the mandible, which are all potential complications of radiation therapy for HNC. This Review describes the efforts to prevent therapy-related complications by presenting the state of the art evidence regarding advanced radiation therapy technology as an organ-sparing approach.     

非小细胞肺癌伽玛刀治疗后并发放射性肺不张分析

目的：回顾分析伽玛刀大分割适形放射治疗非小细胞肺癌（non small cell lung cancer,NSCLC）后并发非肿瘤性肺不张的原因,进一步完善大分割适形放射治疗。方法：488例非小细胞肺癌（NSCLC）分为中央型（262例）和周围型（226例）,分别进行了伽玛刀分次治疗,剂量3Gy-8Gy/次,处方剂量50%-70%剂量线,1次/日,5次/周,连续照射,总次数5-16次,总剂量35Gy-60Gy。结果：非小细胞肺癌中央型伽玛刀治疗3-6月后共出现20例放射性肺不张,而周围型未出现放射性肺不张,两组差异明显。结论：放射性肺不张是肺癌大分割适形放射治疗中很少报道的严重并发症,区分中央型和周围型分别实施治疗可能有效减轻治疗的严重并发症,中央型肺癌进行精确放疗时有必要将1,2级支气管作为剂量限制性器官。     

Preliminary results of conformal radiation therapy for medulloblastoma

Radiation therapy for medulloblastoma consists of postoperative irradiation of the intracranial and spinal subarachnoid volume with an additional boost to the primary site of disease in the posterior fossa. The entire posterior fossa is usually included in the boost volume. Conformal radiation therapy techniques may be used to boost the primary site alone and substantially reduce the dose received by normal tissues, including the supratentorial brain, the middle and inner ear, and the hypothalamus. Using these techniques to irradiate only the tumor bed or residual tumor and not the entire posterior fossa represents a new paradigm in the treatment of medulloblastoma. In this study, we examine the use of conformal radiation therapy in the treatment of 14 patients with medulloblastoma. These patients were treated with multiple static, individually shaped, noncoplanar beams directed at the primary site after craniospinal irradiation. Excluding two patients who had previously received irradiation to the posterior fossa, the mean dose delivered to the primary site was 5715 cGy. Among the medulloblastoma patients (n = 10) who received immediate postoperative radiation therapy, no failures have occurred with a median follow-up of 42 months (range from 30 to 54 months). To demonstrate the differences in the distribution of dose to normal tissues when comparing conventional and conformal techniques, dose-volume histograms of the total brain, middle and inner ear, hypothalamus, and temporal lobe were created and presented for an example case. The neurologic, neuroendocrine, and neurocognitive outcome for patients with medulloblastoma may be influenced with the use of conformal radiation therapy. The use of these techniques should be formally tested in prospective studies of rigorously staged patients with failure rate monitoring.     

鼻咽癌CT模拟定位保护重要器官

CT模拟定位系统能通过逐层准确地勾画出鼻咽肿瘤,包括原发灶和转移灶,周围正常组织和重要器官,清楚地显示肿瘤侵犯范围和敏感器官的三维关系,为照射野的设计提供直观的图像信息.勾画出肿瘤周围的重要器官和组织,如眼、视神经、视交叉、脑神经、颞颌关节、腮腺、垂体、脑干、脊髓等,对正常组织的保护更确切,而这些结构在常规模拟机下是不可视的,设野时可根据肿瘤侵犯范围和周围正常组织的关系决定应对那些周围敏感器官的保护,减少危险器官的照射体积和剂量.它使常规模拟难以实现的复杂的射野设计变得很容易,使照射野设计更准确、合理,避免正常组织的不必要的照射,从而减少放射损伤.     

35例脑胶质瘤术后三维适形放射治疗

背景与目的：脑胶质瘤是颅内常见肿瘤，手术是主要的治疗手段，术后常需补充放射治疗。三维适形放疗是近几年发展起来的一种特殊放射治疗技术。本文旨在初步探讨三维适形放射治疗脑胶质瘤的疗效及不良反应。方法：35例脑胶质瘤患者，其中术后残留34例，术后放疗后复发1例，均接受三维适形放射治疗，予4～6个野共面或非共面照射，3例脑干肿瘤DT50～54Gy／25～27F，其他部位肿瘤DT56～60Gy／28～30F，每日一次，每周5次。结果：随访6-38个月，完全缓解25．7％（9／35），部分缓解48．6％（17／35），稳定14．3％（5／35），疾病进展8．6％（3／35），缓解率为74．3％；6个月、1年、2年生存率分别为94．3％、78．5％、53．9％。CT或MRI显示脑水肿9例，未见严重放射反应发生。结论：采用三维适形放射治疗技术治疗脑胶质瘤安全、有效，无严重不良反应。     

Conventional, conformal, and intensity-modulated radiation therapy treatment planning of external beam radiotherapy for cervical cancer: The impact of tumor regression

PURPOSE: Investigating the impact of tumor regression on the dose within cervical tumors and surrounding organs, comparing conventional, conformal, and intensity-modulated radiotherapy (IMRT) and the need for repeated treatment planning during irradiation. METHODS AND MATERIALS: Fourteen patients with cervical cancer underwent magnetic resonance (MR) imaging before treatment and once during treatment, after about 30 Gy. Target volumes and critical organs were delineated. First conventional, conformal, and IMRT plans were generated. To evaluate the impact of tumor regression, we calculated dose-volume histograms for these plans, using the delineations of the intratreatment MR images. Second conformal and IMRT plans were made based on the delineations of the intratreatment MR images. First and second plans were compared. RESULTS: The average volume receiving 95% of the prescribed dose (43 Gy) by the conventional, conformal, and IMRT plans was, respectively, for the bowel 626 cc, 427 cc, and 232 cc; for the rectum 101 cc, 90 cc, and 60 cc; and for the bladder 89 cc, 70 cc, and 58 cc. The volumes of critical organs at this dose level were significantly reduced using IMRT compared with conventional and conformal planning (p < 0.02 in all cases). After having delivered about 30 Gy external beam radiation therapy, the primary gross tumor volumes decreased on average by 46% (range, 6.1-100%). The target volumes on the intratreatment MR images remained sufficiently covered by the 95% isodose. Second IMRT plans significantly diminished the treated bowel volume, if the primary gross tumor volumes decreased >30 cc. CONCLUSIONS: Intensity-modulated radiation therapy is superior in sparing of critical organs compared with conventional and conformal treatment, with adequate coverage of the target volumes. Intensity-modulated radiation therapy remains superior after 30 Gy external beam radiation therapy, despite tumor regression and internal organ motion. Repeated IMRT planning can improve the sparing of the bowel and rectum in patients with substantial tumor regression.     

First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx)

Purpose: This Phase I study was designed to evaluate the computed tomography (CT) scanner as a device for radiation therapy of human brain tumors (CTRx). This first use in humans of a modified CT for treatment was founded on extensive research experience with canine tumors. An additional objective was to increase the therapeutic radiation dose to tumors compared to normal tissue by concentration of infused contrast material in tumors, an effect available at diagnostic x-ray energies but not at megavoltage energies.

Methods and Materials: A small metastatic brain tumor in each of eight patients received 3–5-weekly fractions of 5 Gy equivalent per fraction from a CT scanner modified to deliver radiation therapy. In each patient, one additional tumor, lying completely outside the volume treated by CTRx, served as a control. The tumor receiving CTRx was treated after infusion of iodinated x-ray contrast media (CM) for dose enhancement. Many of these patients also received conventional 40 Gy whole brain radiation, before, during, or after CTRx treatment.

Results: None of the patients showed adverse reactions to the CM or necrosis of the normal brain from the CTRx boost radiation. Monte Carlo calculations of the radiation dose distributions in a model tumor showed that the CTRx irradiation of tumors carrying 10 mg or more of iodine per gram of tumor was as good or better than the dose distribution from conventional 10-MV X-rays. The treated tumor in two of the patients vanished after four treatments, whereas a control tumor in one patient remained constant and grew 4-fold in another patient.

Conclusion: The CTRx concept effectively combines a modified CT scanner as a diagnostic device, as a simulator dedicated to radiotherapy, and as a treatment machine. Thus, CTRx could be very useful for radiation oncologists in controlling CM-enhanced and other small brain tumors.     

Recent progress in optimizing radiotherapy in chemo-radiotherapy for stage III non-small cell lung cancer

It is logical to tailor radiation dose schedule according to the therapeutic goals, i.e., curative versus pal-liative to achieve the best possible outcome for a given clinical condition. Not all patients with stage III served optimally by administering the same dose of radiation or chemo-radiotherapy regimen. The aim of this study is to update the recent progress in the clinical research in escalation of radiation dose/dose intensity and radiotherapeutic/predictive factors of radiation response which may be useful in guiding high dose radiation therapy in chemo-radiation (CT+RT) for beter outcome. The current literatures (1985–2001) on clinical research in escalation of radiation dose/dose intensity were reviewed for radiotherapeutic factors, which are important in tumor response and therapy outcome. Also reviewed were translational research in genetic/radiobiological/metabolic markers for the identification of useful biomarkers in predicting therapy response to radiation therapy or CT+RT. Reports on combined therapy for stage III NSCLC were also reviewed for the toxicity, tumor response and survival outcome. Factors important for predicting therapy outcome in NSCLC are grouped as follows:

1. Radiotherapeutic factors. The major factors of radiation therapy that play the decisive role for successful outcome include the accurately defined target volume, the dose intensity and total dose of radiation which is high enough to provide local tumor control for the majority of patients, and proper treatment planning, preferably three-dimensional (3-D) conformal radiation therapy planning with which the maximum and optimum dose of radiation can be determined within the limit of normal tissue tolerance.
2. Tumor related factors (anatomic factors). The extent of tumor (tumor stage) is one of the most important prognostic factors affecting the therapy outcome. Tumor size (T stage), anatomical structures involved (T4 versus T3 lesion), and the presence or absence of regional lymph node metastasis have a significant impact on both prognosis and response to appropriate therapy.
3. Host-related factors (clinical factors) that are important in therapy response include performance status, weight loss more than 10% of body weight in the previous 6 months, and associated co-morbidities, i.e., pulmonary and cardiac diseases.
4. Radiobiological/metabolic/genetic factors. Biologic markers resulting from genetic lesions in lung cancer are grouped as follows: a) Radiobiological factors—tumor cell proliferation kinetics (T_pot), hypoxia, intrinsic cellular radiosensitivity, gamma factor, DNA content; b) metabolic/enzymatic factors: increased glucose utilization measured with positron emission tomography-fluorodeoxyglucose (PET-FDG) may be a useful marker for therapy response to radiation therapy and chemotherapy, and also for the definition of biological tumor volume as opposed to anatomic tumor volume by computed tomographic scan, and c) genetic factors: allelic imbalance, methylation, gene overexpression, and polymorphisms.

Current data indicate that there is a dose-response relationship between radiation dose and local tumor control, and also between local tumor control and survival in stage III NSCLC. Therafore, the radiotherapeutic factors, i.e., total radiation dose, fractionation schedule and dose intensity, the use of 3-D conformal radiation to secure the optimum therapeutic ratio are important for improved local tumor control and survival. Future research should be directed towards radiation dose escalation using 3-D conformal therapy to determine the maximum tolerated dose (MTD) of radiation in a setting of chemo-radiotherapy, and the use of this MTD for improved local tumor control and survival. Radiobiological, molecular, and metabolic markers may offer a potential for monitoring tumor response and optimizing radiation therapy accordingly.     

Contemporary brachytherapy approaches in non–small-cell lung cancer

Brachytherapy has the ability to deliver a higher tumor dose compared to external beam irradiation, while sparing normal tissue outside the tumor; it is the most effective means of delivering conformal radiation and can be tailored to clinical circumstances, either at open surgery or in an ambulatory setting, which is currently the preferred method. Intraoperative lung and/or endobronchial brachytherapy in the management of non–small-cell lung cancer offers a good curative potential in patients with accessible localized tumors, well defined and small to moderate in size, that have not metastasized to the lymph nodes and are technically or medically inoperable. Effective palliation can be frequently obtained by endobronchial brachytherapy on an outpatient procedure basis. Brachytherapy administered simultaneously with chemotherapy is better tolerated than a course of external beam irradiation and chemotherapy. J. Surg. Oncol. 1998;69:258–264. © 1998 Wiley-Liss, Inc.     

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.