Conformal radiation therapy for childhood CNS tumors

Radiation therapy plays a central role in the management of many childhood brain tumors. By combining advances in brain tumor imaging with technology to plan and deliver radiation therapy, pediatric brain tumors can be treated with conformal radiation therapy. Through conformal radiation therapy, the radiation dose is targeted to the tumor, which can minimize the dose to normal brain structures. Therefore, by limiting the radiation dose to normal brain tissues, conformal radiation therapy offers the possibility of limiting the long-term side effects of brain irradiation.In this review, we describe different approaches to conformal radiation therapy for pediatric central nervous system tumors including: A) three-dimensional conformal radiation therapy; B) stereotactic radiation therapy with arc photons; C) intensity-modulated radiation therapy; and D) proton beam radiation therapy. We discuss the merits and limitations of these techniques and describe clinical scenarios in which conformal radiation therapy offers advantages over conventional radiation therapy for treating pediatric brain tumors.     

Radiation therapy of ureteral metastases from breast cancer

A series of 6 patients with ureteral metastases from breast carcinoma treated by radiation therapy has been evaluated. Most patients received a tumor dose of 3,600 rads in 3 to 4 weeks, and showed remarkable clinical improvement, with relief of the ureteral obstruction and reversal of symptoms and signs of uremia after radiation therapy. One patient died before an adequate dose of radiation therapy could be given. Early recognition and early treatment of ureteral metastases have been stressed. Radiation therapy techniques have been described.     

Spatial fractionation of the dose in proton therapy: Proton minibeam radiation therapy

In radiation therapy, a renewed interest is emerging for the study of spatially fractionated irradiation. In this article, a few applications using spatial fractionation of the dose will be discussed with a focus on proton minibeam radiation therapy. Examples of calculated dose (1D profiles and 2D dose distributions) and biological evidence obtained so far will be presented for various spatially fractionated techniques GRID, micro- and minibeam radiation therapy. Recent results demonstrating that proton minibeam radiation therapy leads to an increase in normal tissues sparing will be discussed, which opens the door to a dose escalation in the tumour and a possibly efficient treatment of very radioresistant tumours.     

Improving the therapeutic ratio in Hodgkin lymphoma through the use of proton therapy

The risk of serious late complications in Hodgkin lymphoma (HL) survivors has led to a variety of strategies for reducing late treatment effects from both chemotherapy and radiation therapy. With radiation therapy, efforts have included reductions in dose, reductions in the size of the target volume, and most recently, significant reductions in the dose to nontargeted normal tissues at risk for radiation damage, achieved by using the emerging technologies of intensity-modulated radiation therapy and proton therapy (PT). PT is associated with a substantial reduction in radiation dose to critical organs, such as the heart and lungs, and has the potential to improve not only the therapeutic ratio, but also both event-free and overall survival. This review addresses the rationale and evidence for--and the challenges, cost implications, and future development of--PT as an important part of the treatment strategy in HL.     

A treatment planning study comparing whole breast radiation therapy against conformal, IMRT and tomotherapy for accelerated partial breast irradiation.

PURPOSE AND BACKGROUND: Conventional early breast cancer treatment consists of a lumpectomy followed by whole breast radiation therapy. Accelerated partial breast irradiation (APBI) is an investigational approach to post-lumpectomy radiation for early breast cancer. The purpose of this study is to compare four external beam APBI techniques, including tomotherapy, with conventional whole breast irradiation for their radiation conformity index, dose homogeneity index, and dose to organs at risk. METHODS AND MATERIALS: Small-field tangents, three-dimensional conformal radiation therapy, intensity-modulated radiation therapy and helical tomotherapy were compared for each of 15 patients (7 right, 8 left). One radiation conformity and two dose homogeneity indices were used to evaluate the dose to the target. The mean dose to organs at risk was also evaluated. RESULTS: All proposed APBI techniques improved the conformity index significantly over whole breast tangents while maintaining dose homogeneity and without a significant increase in dose to organs at risk. CONCLUSION: The four-field IMRT plan produced the best dosimetric results; however this technique would require appropriate respiratory motion management. An alternative would be to use a four-field conformal technique that is less sensitive to the effects of respiratory motion.     

Radiation dosimetry for radionuclide therapy in a nonmyeloablative strategy

Radionuclide therapy extends the usefulness of radiation from localized disease of multifocal disease by combining radionuclides with disease-seeking drugs, such as antibodies or custom-designed synthetic agents. Like conventional radiotherapy, the effectiveness of targeted radionuclides is ultimately limited by the amount of undesired radiation given to a critical, dose-limiting normal tissue, most often the bone marrow. Because radionuclide therapy relies on biological delivery of radiation, its optimization and characterization are necessarily different than for conventional radiation therapy. However, the principals of radiobiology and of absorbed radiation dose remain important for predicting radiation effects. Fortunately, most radionuclides emit gamma rays that allow the measurement of isotope concentrations in both tumor and normal tissues in the body. By administering a small "test dose" of the intended therapeutic drug, the clinician can predict the radiation dose distribution in the patient. This can serve as a basis to predict therapy effectiveness, optimize drug selection, and select the appropriate drug dose, in order to provide the safest, most effective treatment for each patient. Although treatment planning for individual patients based upon tracer radiation dosimetry is an attractive concept and opportunity, practical considerations may dictate simpler solutions under some circumstances. There is agreement that radiation dosimetry (radiation absorbed dose distribution, cGy) should be utilized to establish the safety of a specific radionuclide drug during drug development, but it is less generally accepted that absorbed radiation dose should be used to determine the dose of radionuclide (radioactivity, GBq) to be administered to a specific patient (i.e., radiation dose-based therapy). However, radiation dosimetry can always be utilized as a tool for developing drugs, assessing clinical results, and establishing the safety of a specific radionuclide drug. Bone marrow dosimetry continues to be a "work in progress." Blood-derived and/or body-derived marrow dosimetry may be acceptable under specific conditions but clearly do not account for marrow and skeletal targeting of radionuclide. Marrow dosimetry can be expected to improve significantly but no method for marrow dosimetry seems likely to account for decreased bone marrow reserve.     

Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie en conditions stéréotaxiques : le cœur

Radiation therapy of breast cancer, Hodgkin lymphoma, lung cancer and others thoracic irradiations induce an ionizing radiation dose to the heart. Irradiation of the heart, associated with patient cardiovascular risk and cancer treatment-induced cardiotoxicity, increase cardiovascular mortality. The long survival after breast or Hodgkin lymphoma irradiation requires watching carefully late treatment toxicity. The over-risk of cardiac events is related to the dose received by the heart and the irradiated cardiac volume. The limitation of cardiac irradiation should be a priority in the planning of thoracic irradiations. Practices have to be modified, using modern techniques to approach of the primary objective of radiotherapy which is to optimize the dose to the target volume, sparing healthy tissues, in this case the heart. We have reviewed the literature on cardiac toxicity induced by conformational tridimensional radiation therapy, intensity-modulated radiation therapy or stereotactic body radiation therapy, in order to evaluate the possibilities to limit cardiotoxicity. Finally, we summarise the recommendations on dose constraints to the heart and coronary arteries.     

Proton therapy in clinical practice

Radiation dose escalation and acceleration improves local control but also increases toxicity.Proton radiation is an emerging therapy for localized cancers that is being sought with increasing frequency by patients.Compared with photon therapy,proton therapy spares more critical structures due to its unique physics.The physical properties of a proton beam make it ideal for clinical applications.By modulating the Bragg peak of protons in energy and time,a conformal radiation dose with or without intensity mo...     

Chordoma Report on Treatment Results in Eighteen Cases

Eighteen patients with a proven histologic diagnosis of chordoma were treated between 1949 and 1982. Four patients received only surgery, 4 patients only radiation therapy, and 10 patients received surgery and postoperative radiation therapy to a varying dose. The results suggest that a higher radiation dose gives longer recurrence-free survival, and that the best long term results can be achieved by combining surgery—as radically as possible—with radiation therapy to a dose level of 60 to 65 Gy. In view of the number of marginal recurrences (2 out of the 14 patients who received radiation therapy), the importance of choosing the right treatment volume is stressed.     

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.     

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。     

Radiation therapy for patients with locally advanced pancreatic cancer: Evolving techniques and treatment strategies

Despite ongoing efforts, patients with locally advanced pancreatic cancer (LAPC) continue to have a dismal prognosis. Such tumors are unresectable, and optimal treatment with chemotherapy and/or radiation therapy is still not established. While chemotherapy is conventionally aimed at preventing metastatic spread of disease, radiation therapy acts locally, improving local control which can potentially improve overall survival and most importantly quality of life. Here, we aim to review the primary literature assessing the role of diverse radiation therapy strategies for patients with LAPC.Many radiation regimens can be considered, and no standard treatment has demonstrated a clear improvement in clinical outcomes. We advise that the modality of choice be dependent on the availability of equipment, the dose and fractionation of treatment, as well as the dose received by normal tissue. Moreover, a candid discussion with the patient concerning treatment goals is equally as essential. Three notable strategies for LAPC are intensity-modulated radiation therapy, volumetric modulated arc therapy, and proton. These radiation modalities tend to have improved dose distribution to the target volumes, while minimizing the radiation dose to surrounding normal tissues. Stereotactic body radiation therapy can also be considered in LAPC patients in cases where the tumor does not invade the duodenum or other neighboring structures. Because of the high doses delivered by stereotactic body radiation therapy, proper respiratory and tumor motion management should be implemented to reduce collateral radiation dosing. Despite improved clinical outcomes with modern radiation modalities, evolving techniques, and more accurate planning, future studies remain essential to elucidate the optimal role for radiation therapy among patients with LAPC.     

De la radiothérapie conventionnelle á l’utilisation de la robotique: des évolutions technologiques et une révolution des pratiques

Since the discovery of X-ray by Röntgen in 1895, the technological evolution of radiation therapy increased swiftly. However, the philosophy remained always the same: delivering higher radiation dose to the target volume while decreasing the dose to the organ at risk. Since the beginning of the 1990s, with conformal radiation therapy development (3DCT), differents techniques appeared. Some of them are derived from 3DCT, such as intensity-modulated radiation therapy, arctherapy, Tomotherapy?, or techniques using gating approach for breath holding. In the frame of stereotactic radiation therapy, the GammaKnife? is already used since 20 years, while new concepts, based on a robotic approach (CyberKnife?), are now available for treatment. Brachytherapy also took advantage from the technological evolution with the new approaches. In the frame of heavy ions, hadrontherapy represents an interesting technique dedicated to special clinical situations including pediatric tumors. In this article, we report an analysis of the technological evolution of radiation therapy.     

The development of radiation necrosis of the brain after radiation therapy

Examination by questionnaire of 102 institutions utilizing radiation therapy throughout the country revealed 97 cases of radiation necrosis of the brain, 41 cases of which have received only one course of radiation therapy with either high energy x-rays or 60Co gamma-rays and that have been histologically confirmed for necrosis. The dose fractionation relationship causing necrosis presumed by Strandquvist's diagram proved to be located along the line with the slope of 0.44 from the interception of 9.9 Gy with a single irradiation. Our own experience of brain tumor and cancer of the paranasal sinus told 2 with developed necrosis (incidence, 0.6%) of 325 cases on radiation therapy at a dose of 50-60 Gy and 5 (incidence, 2.0%) of 253 cases on radiation therapy at a dose of more than 60 Gy.     

New radiotherapy technologies

Conventional radiation therapy has had limited success in curing inoperable lung cancer due to poor local control. There is evidence to suggest that higher doses of radiation will improve local control. In order to safely deliver higher doses of thoracic radiation, advanced treatment techniques are required. Different biologic indices have been utilized to determine whether dose escalation can be safely accomplished, and the results have been reported from many institutions. Tumor motion control aids in treatment since it allows radiation oncologists to more accurately target tumors and therefore to spare more normal tissue from the radiation field. The imaging information from 18-FDG-PET scans also improves target delineation. Advanced treatment delivery techniques, such as three-dimensional conformal radiation therapy, intensity modulated radiation therapy, and stereotactic radiosurgery are also being used to safely escalate the radiation dose. This article explores the current literature on these issues and other advanced radiation therapy techniques.     

Nasopharyngeal carcinomas: analysis of patient, tumor and treatment characteristics determining outcome.

PURPOSE: The present study reviews the experience in treatment of 447 patients with nasopharyngeal carcinomas, analyzing patient, tumor and treatment characteristics determining outcome. MATERIALS AND METHODS: There were 322 males and 125 females, their ages ranging from 7 to 85 years (median, 45 years). Two-hundred and seventy-two patients had World Health Organization (WHO) type 3 carcinomas, 123 patients had T4 tumors and 320 patients had metastatic cervical lymph nodes. Three-hundred and eight patients were treated with radiation therapy alone and 139 patients with chemotherapy in combination with radiation therapy. Cumulative radiation dose to primary tumor ranged from 50 to 76Gy (median, 70Gy) and radiation dose to metastatic cervical lymph nodes ranged from 46 to 74Gy (median, 66Gy). RESULTS: Follow-up ranged from 0.1 to 19.5 years (mean, 7.6 years). Local complete response was achieved in 357 patients. In multivariate analysis, T-classification, cumulative radiation dose to primary tumor and treatment with chemotherapy in combination with radiation therapy predicted local response. Nodal complete response was achieved in 272 patients. In multivariate analysis, N-classification and radiation dose to metastatic cervical lymph nodes predicted nodal response. Local failure was observed in 70 patients, nodal failure in 35 patients and systemic failure in 114 patients. Overall survival, disease-free survival and disease-specific survival were 33, 32 and 37%, respectively, at 10 years. In multivariate analysis, age, T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted overall survival whereas T-classification, N-classification, radiation dose and treatment with chemotherapy in combination with radiation therapy predicted both disease-free survival and disease-specific survival. CONCLUSIONS: Radiation therapy alone appears to be an adequate and viable treatment for patients with early-stage nasopharyngeal carcinomas, whereas treatment with chemotherapy in combination with radiation therapy appears to improve outcome for patients with advanced-stage nasopharyngeal carcinomas.     

An evaluation of radiation exposure from portal films taken during definitive course of pediatric radiotherapy

PURPOSE: Recently, considerable attention has been directed toward computed tomography radiation doses (estimated 1 to 4 cGy) received by pediatric patients, because of the potential for increasing a pediatric patient's risk for developing a secondary malignancy. However, minimal attention has been given to the radiation exposure outside the treatment field resulting from the use of portal films to visualize surrounding anatomy. The objective of this study was to quantify the radiation dose from portal imaging delivered within and outside the radiation treatment field during a course of radiation therapy. METHODS AND MATERIALS: A retrospective review was conducted of the port film dose for 56 consecutive pediatric patients who underwent definitive radiation therapy between January 2001 and January 2002. Treatment locations were classified as brain, 27 patients; abdomen, 11 patients; extremities, 9 patients; pelvis, 6 patients; and thorax, 3 patients. Using the dose per monitor unit and total number of port films taken, the total port film dose for each patient was calculated. In addition, port film dose was quantified for 5 pediatric patients undergoing intensity modulated radiation therapy. RESULTS: The mean total port dose varied from a maximum of 46 cGy for brain to a minimum of 17 cGy for thorax. The mean total port dose as a percentage of prescribed dose was less than 1.25% for all locations in this study; however, most of the port dose is a result of the open-field dose from the double-exposure technique. CONCLUSIONS: Care should be exercised while exposing port films of pediatric patients to minimize both the number of films and corresponding radiation exposure without compromising the quality of treatment delivery. Specifically, the number of monitor units used to image regions outside the treatment field should be kept to a minimum, because such exposure could lead to an increased risk of development of secondary neoplasms.     

Predictive factors in radiotherapy for non-small cell lung cancer: present status

PURPOSE: To evaluate the predictive factors for radiation response in non-small cell lung cancer (NSCLC) and the role of such factors in guiding high dose radiation therapy. METHODS: The first International Workshop on Prognostic and Predictive Factors in Lung Cancer was organized by the Hellenic Cooperative Oncology Group and held in Athens, Greece under the auspices of the International Association for the Study of Lung Cancer. Presentations at this meeting provided the outline of this report, which has also been supplemented with available data from the current literature. RESULTS: The predictive factors for both the natural history and the therapy outcome of NSCLC are grouped as follows: (1) tumor related factors (anatomic factors); the extent of tumor (tumor stage) is one of most important prognostic factors affecting the therapy outcome. Tumor size (T stage), anatomical structures involved (T4 vs. T3 lesion), and the presence of regional lymph node metastasis have a significant impact on both prognosis and response to appropriate therapy; (2) host-related factors (clinical factors) that are important in therapy response include performance status, weight loss of more than 10% of body weight in the previous 6 months, and associated co-morbidities, i.e. pulmonary and cardiac diseases; (3) technical factors of radiation therapy which play a decisive role in successful outcome. The target volume should be defined accurately using modern imaging studies. The radiation dose fractionation schedule, in terms of the dose intensity and total dose, should be high enough to provide local tumor control in the majority of patients. Three-dimensional (3-D) conformal planning is an essential tool in dose escalation studies to determine the maximum tolerated dose of radiation; (4) biological/radiobiological/metabolic factors. Biologic markers resulting from genetic lesions in lung cancer are grouped as follows: (a) oncogene amplification and overexpression (aberrant gene expression) and mutated tumor suppressor genes -- ras gene, myc gene, HER-2/neu and survivin gene, p53 and mutated beta-tubulin gene; (b) tumor biologic/radiobiologic factors -- tumor cell proliferation kinetics, hypoxia, intrinsic cellular radiosensitivity, gamma factor, and DNA content; (c) enzymes and hormones: neuron-specific enolase, serum lactate dehydrogenase, and enhanced glucose metabolic rate supported by increased glucose transporter protein. The surviving fraction of tumor cells at 2.0 Gy of radiation (SF2) as a measure of intrinsic tumor cell radiosensitivity, potential doubling time (T(Pot)) as a measure of the rate of tumor cell proliferation and gamma factor representing the slope of the survival curve at 50% survival rate are being investigated as potential predictors for therapy response. Enhanced glucose utilization, a hallmark of malignant transformation, is being studied as a potential monitor for therapy response by using PET-FDG. CONCLUSION: 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. Therapeutic factors, i.e. total radiation dose, fractionation schedule and dose intensity, and 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 chemo-radiotherapy, and the use of this MTD for improved local tumor control and survival. Radiobiological, molecular, and metabolic markers may have potential for monitoring tumor response and optimizing radiation therapy.     

头颈部肿瘤自适应放疗的研究进展

调强放射治疗(intensity-modulated radiation therapy,IMRT)是头颈部恶性肿瘤的重要治疗方法之一。但在IMRT过程中,摆位误差、解剖结构的移位及变形、肿瘤退缩或进展及形状改变等,可导致靶区和危及器官的照射剂量和体积出现“偏差”,影响IMRT的精确性。图像引导的放射治疗(image-guidedradiotherapy,IGRT)可部分纠正摆位误差,从而提高放疗精度,但不能解决非刚性误差以及解剖结构变化带来的剂量差异。自适应放射治疗(adaptive radiation therapy,ART)是在IMRT和IGRT基础上出现的新型放疗技术,能修正IMRT和IGRT靶区和危及器官的偏差。通过患者图像、剂量等反馈信息对原治疗计划重新优化和调整,这是一种基于反馈控制理论的治疗策略。其目的是使放射治疗更加精确化、个体化。