Radiotherapy with high-energy charged particles has become an attractive therapeutic option for patients with several tumour types because this approach better spares healthy tissue from radiation ...than conventional photon therapy. The cost associated with the delivery of charged particles, however, is higher than that of even the most elaborate photon-delivery technologies. Reliable evidence of the relative cost-effectiveness of both modalities can only come from the results of randomized clinical trials. Thus, the hurdles that currently limit direct comparisons of these two approaches in clinical trials, especially those related to insurance coverage, should be removed. Herein, we review several randomized trials of charged-particle therapies that are ongoing, with results that will enable selective delivery to patients who are most likely to benefit from them. We also discuss aspects related to radiobiology, including the immune response and hypoxia, which will need to be taken into consideration in future randomized trials to fully exploit the potential of charged particles.
The use of charged particle therapy to control tumours non-invasively offers advantages over conventional radiotherapy. Protons and heavy ions deposit energy far more selectively than X-rays, ...allowing a higher local control of the tumour, a lower probability of damage to healthy tissue, low risk of complications and the chance for a rapid recovery after therapy. Charged particles are also useful for treating tumours located in areas that surround tissues that are radiosensitive and in anatomical sites where surgical access is limited. Current trial outcomes indicate that accelerated ions can potentially replace surgery for radical cancer treatments, which might be beneficial as the success of surgical cancer treatments are largely dependent on the expertise and experience of the surgeon and the location of the tumour. However, to date, only a small number of controlled randomized clinical trials have made comparisons between particle therapy and X-rays. Therefore, although the potential advantages are clear and supported by data, the cost:benefit ratio remains controversial. Research in medical physics and radiobiology is focusing on reducing the costs and increasing the benefits of this treatment.
Immunotherapy, specifically the introduction of immune checkpoint inhibitors, has transformed the treatment of cancer, enabling long-term tumour control even in individuals with advanced-stage ...disease. Unfortunately, only a small subset of patients show a response to currently available immunotherapies. Despite a growing consensus that combining immune checkpoint inhibitors with radiotherapy can increase response rates, this approach might be limited by the development of persistent radiation-induced immunosuppression. The ultimate goal of combining immunotherapy with radiotherapy is to induce a shift from an ineffective, pre-existing immune response to a long-lasting, therapy-induced immune response at all sites of disease. To achieve this goal and enable the adaptation and monitoring of individualized treatment approaches, assessment of the dynamic changes in the immune system at the patient level is essential. In this Review, we summarize the available clinical data, including forthcoming methods to assess the immune response to radiotherapy at the patient level, ranging from serum biomarkers to imaging techniques that enable investigation of immune cell dynamics in patients. Furthermore, we discuss modelling approaches that have been developed to predict the interaction of immunotherapy with radiotherapy, and highlight how they could be combined with biomarkers of antitumour immunity to optimize radiotherapy regimens and maximize their synergy with immunotherapy.
Radiotherapy is one of the most common and effective therapies for cancer. Generally, patients are treated with X-rays produced by electron accelerators. Many years ago, researchers proposed that ...high-energy charged particles could be used for this purpose, owing to their physical and radiobiological advantages compared with X-rays. Particle therapy is an emerging technique in radiotherapy. Protons and carbon ions have been used for treating many different solid cancers, and several new centers with large accelerators are under construction. Debate continues on the cost:benefit ratio of this technique, that is, on whether the high costs of accelerators and beam delivery in particle therapy are justified by a clear clinical advantage. This Review considers the present clinical results in the field, and identifies and discusses the research questions that have resulted with this technique.
Low‐Grade Gliomas Forst, Deborah A.; Nahed, Brian V.; Loeffler, Jay S. ...
The oncologist (Dayton, Ohio),
April 2014, Volume:
19, Issue:
4
Journal Article
Peer reviewed
Open access
Low‐grade gliomas (LGGs) are a diverse group of primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course with longer‐term survival in ...comparison with high‐grade gliomas. Treatment options include observation, surgery, radiation, chemotherapy, or a combined approach, and management is individualized based on tumor location, histology, molecular profile, and patient characteristics. Moreover, in this type of brain tumor with a relatively good prognosis and prolonged survival, the potential benefits of treatment must be carefully weighed against potential treatment‐related risks.
We review in this article current management strategies for LGG, including surgery, radiotherapy, and chemotherapy. In addition, the importance of profiling the genetic and molecular properties of LGGs in the development of targeted anticancer therapies is also reviewed. Finally, given the prevalence of these tumors in otherwise healthy young patients, the impact of treatment on neurocognitive function and quality of life is also evaluated.
This article reviews current management strategies for low‐grade gliomas (LGG), including surgery, radiotherapy, and chemotherapy. In addition, the importance of profiling the genetic and molecular properties of LGGs in the development of targeted anticancer therapies is also reviewed. Finally, given the prevalence of these tumors in otherwise healthy young patients, the impact of treatment on neurocognitive function and quality of life is also evaluated.
Context:
Optimal management of pituitary adenomas involves consideration of the roles of medical therapy, surgery, and radiation therapy. The different forms of radiation therapy and their results ...are reviewed here.
Evidence Acquisition:
A literature search through the U.S. National Library of Medicine was used to identify and review clinical experiences of radiation therapy in the management of pituitary adenomas. Emphasis was placed on studies within the last 5–10 yr, with 5 or more years of follow-up data, and of reasonable quality of data. Older studies with larger numbers or particular significance are also highlighted.
Evidence Synthesis:
Success of radiation therapy in controlling tumor growth is high, 90–100% in most series, regardless of radiation technique and adenoma subtype. Success in achieving hormonal normalization in secretory tumors is more variable because of differences in patient population, radiation technique, and doses employed and variation of the definition of success. Complete biochemical remission is generally achieved in 50% of patients at 10 yr after treatment for most adenomas. Higher rates of normalization can be achieved with additional medical therapy. Hypopituitarism is an expectant result of radiation therapy. Overall rate of other treatment-related adverse effects is low.
Conclusions:
Radiation therapy should be considered in the management of patients with pituitary adenomas, particularly when medical and surgical options have been exhausted. Because response evolves slowly over many years and because hypopituitarism is likely to occur, patients should be counseled on the importance of continued endocrinological surveillance and medical management.
Primary CNS lymphoma Batchelor, Tracy; Loeffler, Jay S
Journal of clinical oncology,
2006-Mar-10, Volume:
24, Issue:
8
Journal Article
Peer reviewed
Primary CNS lymphoma (PCNSL), an uncommon form of extranodal non-Hodgkin's lymphoma (NHL), has increased in incidence during the last three decades and occurs in both immunocompromised and ...immunocompetent hosts. PCNSL in immunocompetent patients is associated with unique diagnostic, prognostic, and therapeutic issues, and the management of this malignancy is different from that of other forms of extranodal NHL. Characteristic imaging features should be suggestive of the diagnosis, avoidance of corticosteroids, if possible, and early neurosurgical consultation for stereotactic biopsy. Because PCNSL may involve the brain, CSF, and eyes, diagnostic evaluation should include assessment of all of these regions as well as screening for possible occult systemic disease. Resection provides no therapeutic benefit and should be reserved for the rare patient with neurologic deterioration due to brain herniation. Whole-brain radiation therapy (WBRT) alone is insufficient for durable tumor control and is associated with a high risk of neurotoxicity in patients older than age 60. Neurotoxicity typically is associated with significant cognitive, motor, and autonomic dysfunction, and has a negative impact on quality of life. Chemotherapy and WBRT together improve tumor response rates and survival compared with WBRT alone. Methotrexate-based multiagent chemotherapy without WBRT is associated with similar tumor response rates and survival compared with regimens that include WBRT, although controlled trials have not been performed. The risk of neurotoxicity is lower in patients treated with chemotherapy alone.
Multidisciplinary Management of Brain Metastases Eichler, April F.; Loeffler, Jay S.
The oncologist (Dayton, Ohio),
July 2007, 2007-Jul, 2007-07-01, 20070701, Volume:
12, Issue:
7
Journal Article
Peer reviewed
Open access
Learning Objectives
After completing this course, the reader will be able to:
Identify the clinical factors that predict survival after a diagnosis of brain metastasis.
Select appropriate ...multidisciplinary treatments for patients with new and recurrent brain metastases.
Describe the circumstances in which focal therapy, such as surgery or stereotactic radiosurgery, is likely to be beneficial for patients with brain metastases.
Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Metastatic brain tumors are the most common intracranial neoplasms in adults. The incidence of brain metastases appears to be rising as a result of superior imaging modalities, earlier detection, and more effective treatment of systemic disease. Therapeutic approaches to brain metastases include surgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and chemotherapy. Treatment decisions must take into account clinical prognostic factors in order to maximize survival and neurologic function whilst avoiding unnecessary treatments. The goal of this article is to review important prognostic factors that may guide treatment selection, discuss the roles of surgery, radiation, and chemotherapy in the treatment of patients with brain metastases, and present new directions in brain metastasis therapy under active investigation. In the future, patients will benefit from a multidisciplinary approach focused on the integration of surgical, radiation, and chemotherapeutic options with the goal of prolonging survival, preserving neurologic and neurocognitive function, and maximizing quality of life.
Disclosure of potential conflicts of interest is found at the end of this article.
Brain metastases are a serious obstacle in the treatment of patients with solid tumors and contribute to the morbidity and mortality of these cancers. It is speculated that the frequency of brain ...metastasis is increasing for several reasons, including improved systemic therapy and survival, and detection of metastases in asymptomatic patients. The lack of preclinical models that recapitulate the clinical setting and the exclusion of patients with brain metastases from most clinical trials have slowed progress. Molecular factors contributing to brain metastases are being elucidated, such as genes involved in cell adhesion, extravasation, metabolism, and cellular signaling. Furthermore, the role of the unique brain microenvironment is beginning to be explored. Although the presence and function of the blood-brain barrier in metastatic tumors is still poorly understood, it is likely that some tumor cells are protected from therapeutics by the blood-tumor barrier, creating a sanctuary site. This Review discusses what is known about the biology of brain metastases, what preclinical models are available to study the disease, and which novel therapeutic strategies are being studied in patients.
PDF
