Overview: Where does radiation therapy fit in the spectrum of liver cancer local-regional therapies?

Experience with radiation therapy for the treatment of hepatocellular carcinoma (HCC) and liver metastases has increased rapidly in the past decade. This is principally because of advances in imaging and radiation techniques that can conform high doses to focal cancers and to a better understanding of how to avoid radiation-induced liver toxicity. Guidelines on how to use radiation therapy safely are becoming more clearly established, and reports of tumor control at 2 to 5 years show the potential for cure after radiation therapy for early-stage HCC and liver metastases. For both HCC and liver metastases, the best outcomes after radiation therapy are found in patients with fewer than 3 lesions that are <6 cm in size, with intact liver function and no extrahepatic metastases. There is a strong rationale for using radiation therapy in patients unsuitable for or with expected poor outcomes after standard local-regional therapies. These patients tend to have advanced tumors (large, multifocal, or invading vessels) and/or impaired liver function, reducing the chance of cure and increasing the chance of toxicity. In these patients, the benefits of radiation therapy over systemic therapy or best supportive therapy should be established in randomized trials.     

Conformal chemoradiation for primary and metastatic liver malignancies

Historically, radiation therapy has played a minor role in the management of patients with unresectable primary hepatobiliary malignancies and liver metastases from colorectal cancer. This can be attributed chiefly to the low tolerance of the whole liver to radiation. Three-dimensional radiation planning techniques have allowed much higher doses of radiation to be delivered to focal liver tumors, while sparing the majority of the normal liver. When combined with fluorodeoxyuridine (FUdR), high-dose focal liver radiation is associated with excellent response rates, local control, and survival in patients with large unresectable tumors. There appears to be a radiation dose response for intrahepatic malignancies. Advancements in tumor imaging, radiation techniques that can safely deliver higher doses of radiation, novel tumor radiation sensitizers, and normal-tissue radioprotectors should substantially improve the outcome of patients with unresectable intrahepatic malignancies treated with chemoradiation.     

Trends in radiation therapy for the treatment of metastatic and oligometastatic disease in 2010

The role of radiation therapy in metastatic disease has evolved from palliative to potentially curative intent for selected oligometastases using highly conformal radiation techniques, including extracranial stereotactic body radiotherapy (SBRT) in the last decade. SBRT has a potential to use small numbers of large doses aiming at achieving high rates of local control while preserving the quality of life even in highly pretreated patients. A wide range of techniques, doses, and dose fractionation schedules can be found. However, the 2-year local control is around 80% for lung metastases with corresponding 2-year survival of 50%, and a 5% rate of grade III or higher radiation toxicities. The 2-year local control varies between 57 and 92% for liver metastases and radiation-induced liver disease is exceptional provided that 700 cm3 of healthy liver are irradiated to less than 15 Gy in three fractions or more. Stereotactic radiation is also particularly interesting for spinal, and cranial metastases and reirradiations. Also, it has come into focus that associations of chemotherapy or targeted therapies and radiation may be used for optimized treatment of limited metastatic disease and that irradiation of the primary tumor may be recommended in the context of metastatic disease. It also appears that the definition of target volumes for palliative radiation therapy and scores to assess for life expectancy-based need for irradiation should be improved.     

原发性肝癌手术联合放疗的近期研究进展

手术是原发性肝癌的主要根治性治疗手段,而术后复发率高是影响其疗效的主要因素。随着医学技术的发展,放疗对于肝癌治疗的安全性和有效性已得到广泛证实。本文从肝癌合并门静脉癌栓的术前及术后放疗、窄切缘术后的辅助放疗、微血管侵犯术后的辅助放疗、肝移植手术前的桥接放疗、局限于肝内初始不可切除肝癌的转化性降期放疗方面,探讨肝癌手术前后放疗的现状和未来前景。虽然放疗是肝癌的有效治疗手段之一,但仍需前瞻性、随机、对照的Ⅲ期研究,以获得更高级别的循证医学证据,进一步确立放疗在肝癌治疗中的地位。     

New devices in radiation oncology

The development of sophisticated conformal radiation techniques, such as intensity-modulated radiation therapy, image-guided radiation therapy, adaptative radiation therapy, and radiosurgery, implies precise and accurate targeting. To achieve this goal, a lot of new devices and techniques have been designed and are now available in radiation therapy departments : modern 3D-imaging systems, sophisticated treatment planning systems, breathing-adapted radiotherapy equipments (for gating and tracking techniques), in-room 3D-imaging systems, tomotherapy, etc. Purpose of this review is to briefly present the new equipments which are now used in radiation therapy departments in conformal therapy.     

Évaluation de la réponse thérapeutique après radiothérapie stéréotaxique des lésions tumorales hépatiques

Stereotactic body radiation therapy takes more and more an important place in the therapeutic arsenal of primitive and secondary liver tumours. The administration of ablative radiation doses can result in specific changes to both the tumour and the healthy hepatic parenchyma, relative to conventional radiation therapy, making the assessment of local changes after stereotactic body radiation therapy, in terms of local control and reaction of healthy tissue, often difficult. It is mandatory to standardize and simplify our evaluation criteria to benefit from a better understanding of the effectiveness of this new treatment modality and allow better reproducibility of available imaging exams. This article presents a literature review of the various radiological changes observed after stereotactic body radiation therapy for liver tumours according to the multiple assessment methods used to determine local control. From the data available, we recommend using modified RECIST criteria proposed by the American Association for the Study of Liver Diseases (AASLD), as objective and relevant criteria of local control after stereotactic body radiation therapy for liver tumours.     

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.     

The role of radiotherapy in the treatment of liver metastases

Radiotherapy has historically played a minor role in the treatment of patients with unresectable liver metastases from colorectal cancer and other malignancies. This can be attributed chiefly to the low tolerance of the whole liver to radiation. High-precision radiotherapy planning techniques have allowed much higher doses of radiation to be delivered safely to focal liver metastases, while sparing most of the normal liver. When combined with hepatic arterial fluorodeoxyuridine, high-dose focal liver radiotherapy is associated with excellent response rates, local control, and survival in patients with unresectable liver metastases from colorectal cancer. Radiotherapy, with and without concurrent systemic chemotherapy, has also been used with encouraging outcomes for patients with liver metastases from colorectal cancer and other cancers. There appears to be a radiation dose response for liver metastases; tumors treated with doses of 70 Gy or greater are likelier to have durable local control. Advancements in tumor imaging, in radiotherapy techniques that will allow the safe delivery of higher doses of radiation, and in novel tumor radiation sensitizers and normal tissue radioprotectors should substantially improve the outcome of patients with unresectable liver metastases treated with radiotherapy.     

Stereotactic body radiation therapy for liver tumours

Recent improvements in radiation therapy delivery techniques provide new tools to treat patients with liver-confined disease, either with hepatocellular carcinoma or liver metastases. An appropriate selection of the patients made during a multidisciplinary specialized tumour board is mandatory. It should be based on the disease extension, an accurate evaluation of the comorbidities and the liver functions. The added value of this approach has to be evaluated in well-designed trials, alone or in combination with other treatments such as surgery, local treatments, chemoembolization and/or chemotherapy with or without targeted agents. Stereotactic body radiation therapy should be applied under strict conditions of expertise of the radiation oncology departments, including equipment and educational training programmes. However under these conditions, preliminary results seems highly encouraging in terms of local control and tolerance but should be confirmed in large controlled prospective trials.     

Imaging and image-guided radiation therapy in liver cancer

Imaging for radiation therapy treatment planning and delivery is a critical component of the radiation planning process for liver cancer. Because of the lack of inherent contrast between liver tumors and the surrounding liver, intravenous contrast is required for accurate target delineation on the planning computed tomography scan. The appropriate phase of contrast is tumor specific, with arterial phase imaging usually used to define hepatocellular carcinoma and venous phase imaging for vascular thrombosis related to hepatocellular carcinoma and most types of liver metastases. Breathing motion and changes in the liver position day to day may be substantial and need to be considered at the time of radiation planning and treatment. Many types of integrated imaging-radiation treatment systems and image-guidance strategies are available to produce volumetric and/or planar imaging at the time of treatment delivery to reduce the negative impact of geometric changes that may occur. Image-guided radiation therapy facilitates reduced PTV margins and dose escalation and improves the precision of radiation therapy, so the prescribed doses are more likely to represent those actually delivered.     

Treatment of hepatocellular carcinoma (HCC) by intra-arterial infusion of radio-emitter compounds: trans-arterial radio-embolisation of HCC

Traditional radiotherapy is only effective in treating hepatocellular cancer (HCC) in doses above 50 Gy, but this is above the recommended liver radiation exposure of about 35 Gy, which is an important limitation making this treatment unsuitable for routine clinical practice. Trans-arterial radio-embolisation (TARE), consists of delivery of compounds linked to radio-emitter particles which end up in hepatic end-arterioles or show affinity for the neoplasm itself, allowing localised delivery of doses beyond 120 Gy. These are well tolerated in patients treated with this type of internal radiation therapy. TARE for HCC is used for palliative treatment of advanced disease which cannot be treated in other ways, or for tumour down-staging before liver transplantation, or as adjuvant therapy for surgically resected HCC. Tumour response after TARE is between 25% and 60% if assessed by using RECIST criteria, and 80% by EASL criteria. In this review we outline the advantages and limitations of radio-emitter therapy including 131-I, 90-Y and 188-Re. We include several observational, and all comparative studies using these compounds. In particular we compare TARE to trans-arterial chemo-embolisation and other intra-arterial techniques.     

Postmastectomy Radiation Therapy Planning After Immediate Implant-based Reconstruction Using the European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice Consensus Guidelines for Target Volume Delineation

AimsTo evaluate how common radiation therapy techniques perform in the setting of the new European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) delineation recommendations for immediate breast reconstruction (IBR).Materials and methodsSeven Danish radiation therapy centres and six international European centres participated in this project. Two breast cancer cases (one left-sided and one right-sided) with a retropectoral implant were chosen for radiation therapy planning using deep-inspiration breath-hold. Target volumes were delineated according to ESTRO-ACROP delineation recommendations. The centres were asked to plan the cases using any radiation therapy technique according to the Danish Breast Cancer Group plan objectives.ResultsIn total, 35 treatment plans were collected. Half of the submitted plans, for both the left-sided and the right-sided case, used the field-in-field (FiF) technique (nine for each), a quarter used volumetric arc radiation therapy (VMAT; five for right-sided, four for left-sided) and the remaining quarter was a mix of inverse intensity-modulated radiation therapy (IMRT), helicoidal therapy and hybrid (combined open fields and VMAT) techniques. Mean clinical target volume doses were in the range 99–102% of the prescribed dose. The median FiF mean heart dose (MHD) for right-sided radiation therapy was 1 Gy (range 0.8–3.7) and 5.2 Gy for left-sided radiation therapy (range 2.2–6.5). For right-sided radiation therapy, the median VMAT MHD was 3.42 Gy, for IMRT was 2.3 Gy and for helicoidal therapy was 5.1 Gy. For left-sided radiation therapy, the median VMAT MHD was 6.3 Gy, for IMRT was 7.8 Gy and for helicoidal therapy was 7.3 Gy.ConclusionsDifferent radiation therapy techniques could be used to plan radiation therapy in the setting of IBR. FiF provided good coverage with acceptable organ at risk doses. The best dose distribution results as a trade-off between the objectives of target volume coverage and high-dose organ at risk inclusion. The radiation therapy technique affects the interplay between these objectives.     

Imaging changes after stereotactic body radiation therapy for lung and liver tumors

Stereotactic body radiation therapy (SBRT) is gaining wide acceptance as a treatment modality for lung and liver tumors, and it is crucial to make an accurate evaluation of the local effects of ablative doses of radiation in terms of local tumor control and normal tissue reaction or damage. The very complex radiation dose distribution of SBRT, the use of a large number of non-opposing and noncoplanar beams, and the delivery of individual ablative doses of radiation may cause substantially different radiographic appearance on diagnostic imaging compared with conventional radiation therapy. Different patterns of radiographic changes have been observed in the lung and liver after SBRT. This article reviews the post-SBRT imaging changes in the lung and liver. Since computed tomography and PET are the most commonly used diagnostic imaging tools for monitoring lung tumor and computed tomography for liver tumors, this article will focus on the changes observed on those imaging modalities.     

Hepatic radiation toxicity: avoidance and amelioration

The refinement of radiation therapy and radioembolization techniques has led to a resurgent interest in radiation-induced liver disease (RILD). The awareness of technical and clinical parameters that influence the chance of RILD is important to guide patient selection and toxicity minimization strategies. "Classic" RILD is characterized by anicteric ascites and hepatomegaly and is unlikely to occur after a mean liver dose of approximately 30 Gy in conventional fractionation. By maintaining a low mean liver dose and sparing a "critical volume" of liver from radiation, stereotactic delivery techniques allow for the safe administration of higher tumor doses. Caution must be exercised for patients with hepatocellular carcinoma or pre-existing liver disease (eg, Child-Pugh score of B or C) because they are more susceptible to RILD that can manifest in a nonclassic pattern. Although no pharmacologic interventions have yet been proven to mitigate RILD, preclinical research shows the potential for therapies targeting transforming growth factor-β and for the transplantation of stem cells, hepatocytes, and liver progenitor cells as strategies that may restore liver function. Also, in the clinical setting of veno-occlusive liver disease after high-dose chemotherapy, agents with fibrinolytic and antithrombotic properties can reverse liver failure, suggesting a possible role in the setting of RILD.     

Les doses dues à l’imagerie numérique pour le contrôle de positionnement du patient en radiothérapie : comment les prendre en compte ?

The patient positioning and repositioning control in radiation therapy all along the treatment can be conducted using a variety of X-ray sources and imaging detector devices. The development of image guided radiation therapy techniques leads to more frequent use of this imaging control. In this article we summarize the current methods for measuring the dose delivered by X-ray imaging devices used in radiation therapy, as well as basic proposals to take account of these imaging doses for prescribing, recording and reporting radiation therapy treatment.     

原发性肝癌合并门静脉癌栓的放射治疗进展

原发性肝癌合并门静脉癌栓的发病率相当高,治疗效果差、生存期短、合并症多,一直是肝癌研究领域中重要且难度高的课题。近年来放射治疗运用于原发性肝癌合并门静脉癌栓的报道越来越多,包括三维适形放疗、立体定向放疗、质子放疗、同位素内放疗以放疗为主的综合治疗等,主要根据患者的病情及癌栓情况合理制定治疗措施,进行个体化和序贯性的治疗。本文就放射治疗原发性肝癌合并门静脉癌栓的相关研究进展作一综述。     

Cost-Effectiveness of Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy in Treating Brain Metastases

Single-fraction stereotactic radiosurgery (SRS) is a highly used tool in managing brain metastases, alongside its multifraction counterpart – stereotactic body radiation therapy (SBRT). These radiation therapy techniques have been associated with excellent clinical outcomes, such as decreased local recurrence, increased survival, and improved palliative effects. However, present literature concerning the cost-effectiveness of these techniques remain scarce. Based on the current procedure terminology codes involving services provided during radiation consultation, treatment, and follow-up in our institution, 3-fraction SBRT with a 3-dimensional plan and intensity modulated radiation therapy cost 27% and 17% more than SRS, respectively. A 32% and 34% price increase can, respectively, be seen in 5-fraction SBRT with 3-dimensional plan and intensity modulated radiation therapy delivery sessions relative to 3-fraction SBRT administration. Cost savings between these procedures were associated with the radiation therapy delivery sessions instead of the treatment planning process. These analyses indicate that SRS appears to be a less expensive and time-intensive option than SBRT in our institution. However, additional comparative analyses regarding SRS and SBRT are needed to explore the clinical and financial benefits of these radiation therapy techniques.     

Body Image: a Critical Psychosocial Issue for Patients With Head and Neck Cancer

There is substantial and growing interest in the use of local therapies to treat patients with metastatic cancer, especially those deemed to have “oligometastatic” disease. Much of the literature to date consists of reports on metastasectomy for liver and lung metastases. Non-surgical minimally or non-invasive treatments including thermal ablation, irreversible electroporation, and high-dose radiation therapy (stereotactic ablative radiation therapy) can also be used in the treatment of primary and secondary tumors, including in the treatment of liver metastases. In this review, we discuss the rationale for using these ablative treatments in the treatment of liver metastases including similarities and differences between them.     

Techniques de radiothérapie guidée par l’image (IGRT)

In recent years, the new irradiation techniques as the conformal 3D radiation therapy and the intensity modulated radiation therapy (IMRT) have been strongly correlated with the technological developments. These techniques have heightened the necessity of a thorough localization and precise definition of the volumes of interest. In response to this challenge, new technologies known as image-guided radiation therapy (IGRT) have been developed and can be used in two of the main steps in external beam radiation therapy: 1) treatment preparation by determining target volume; and 2) treatment delivery by positioning the patient and localizing the target volume. Inthis paper, we focus on different IGRT techniques used in the second step: X-ray imaging (kV or MV), such as the ExacTrac® system and Cyberknife® imaging system, conventional in-room computed tomography (CT), cone beam computed tomography (CBCT), and non-ionizing imaging techniques, such as the detection of magnetic fiducials and tracking the surface of patients using video imaging.