Human papilloma virus (HPV)-positive oropharyngeal cancer (OPC) is increasingly prevalent and has a favorable prognosis compared to HPV-negative OPC and other head and neck malignancies associated with smoking and alcoho...Human papilloma virus (HPV)-positive oropharyngeal cancer (OPC) is increasingly prevalent and has a favorable prognosis compared to HPV-negative OPC and other head and neck malignancies associated with smoking and alcohol. De-escalation of definitive therapy for HPV-positive OPC is an attractive strategy aiming to maintain oncologic efficacy while reducing short-term and long-term toxicities and improving quality of life. In this article, we outline approaches to de-escalation including use of alternative systemic therapies, reduction in dose of systemic therapy, and reductions in radiation dose and/or volume. We also highlight successes and cautionary outcomes from de-escalation studies and advocate for a personalized approach to future de-escalation trials in HPV-positive OPC.
Fundamental axioms of elective nodal irradiation (ENI) for head and neck cancers merit re-examination in contemporary practice. Standard ENI doses to volumes bordering critical organs-at-risk increased during the transit...Fundamental axioms of elective nodal irradiation (ENI) for head and neck cancers merit re-examination in contemporary practice. Standard ENI doses to volumes bordering critical organs-at-risk increased during the transition from two-dimensional radiation planning to intensity-modulated radiotherapy, despite improvements in detection of occult nodal metastases with modern imaging, use of concurrent chemotherapy, and identification of human papillomavirus (HPV)-related radiosensitivity. Historical large ENI volumes covering low-risk nodal regions continue to be commonly used even as awareness grows regarding the predominant pattern-of-failure within existing gross disease. In this review, we outline principles for de-escalating head and neck ENI dose and volume and highlight the emerging paradigm of ENI omission. We also propose a three-part approach to ENI de-escalation, the rationale for early adoption of de-escalated ENI in the absence of level-one evidence, and strategies to promote early adoption in light of modest equipoise and an inflection point towards changing the status quo.
Chimeric antigen receptor (CAR) T-cell receptor therapy has transformed outcomes for patients with relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL). It is currently approved in the third line for all pat...Chimeric antigen receptor (CAR) T-cell receptor therapy has transformed outcomes for patients with relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL). It is currently approved in the third line for all patients and in the second line for early relapsed or primary refractory disease. Although CAR T cell therapy offers the potential for improved outcomes, its use may also include logistical delays related to referral, medical, social, and financial clearance as well as manufacturing time; more than half of patients experience disease recurrence or progression while awaiting CAR T infusion. Bridging radiotherapy, defined as radiation delivered between the decision to pursue CAR T and infusion of CAR T cells, has become an attractive option for patients who would benefit from local disease control or palliation of symptoms. Additionally, patterns of failure analyses have revealed a dominant role of local disease progression, which has fueled investigations on bridging and early salvage radiation to improve long-term outcomes in patients, particularly those with localized or high-risk disease. Several potential mechanisms by which radiation therapy may improve CAR T efficacy have been proposed that include cytoreduction, tumor debulking, neutralization of immunosuppressive hypoxic and acidic tumor microenvironments, and immunologic and pro-apoptotic synergy between radiation and CAR T. Prospective clinical trials and translational work are ongoing and are needed to inform our conceptual understanding of potential mechanisms by which radiation therapy may improve CAR T efficacy and toxicity, identify which patients may be most likely to benefit, and confirm proposed clinical benefits.
Survival outcomes for multiple myeloma (MM) have drastically improved over the past two decades with the advent of highly effective biologic agents and integration of autologous stem cell transplant (ASCT) for select pat...Survival outcomes for multiple myeloma (MM) have drastically improved over the past two decades with the advent of highly effective biologic agents and integration of autologous stem cell transplant (ASCT) for select patients. Despite these advances, MM remains an incurable disease and duration of remission decreases with each relapse. Palliative radiotherapy (RT) for MM, including treatment of pain, relief of compression, and prevention of fracture, is highly effective and generally well tolerated. Though RT can be delivered concurrently with biologic agents, caution should be exercised for potential added hematologic toxicity that may disrupt systemic therapy, especially in heavily pretreated patients, who have limited bone marrow reserve. In this review, we discuss the safety of RT with biologic agents (proteasome inhibitors, immunomodulators, monoclonal antibodies), review indications for palliative RT in MM, and present a framework for how to personalize RT based on goals of treatment, classification of uncomplicated versus complicated lesions, and patient and lesion characteristics. Additionally, we discuss the emerging role of bridging RT prior to chimeric antigen receptor (CAR) T-cell therapy.
Total body irradiation (TBI) has been an important component of myeloablative and nonmyeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) for decades. Playing a dual role, bot...Total body irradiation (TBI) has been an important component of myeloablative and nonmyeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) for decades. Playing a dual role, both cytotoxic and immuno-suppressive, TBI eliminates residual disease while also impairing the immune system from rejecting the foreign donor cells being transplanted. Unlike chemotherapy, radiotherapy is not hampered by perfusion, diffusion, or the blood-barrier effect and can effectively treat sanctuary sites. However, radiotherapy is subject to radiobiological trade-offs between destroying cancer cells, preserving immune and hematopoietic stem cells, and causing various adverse effects in normal tissue. Optimizing the immuno- suppressive effect of fractionated TBI while sparing normal organs requires careful consideration of total dose, dose per fraction, dose rate, target dose coverage, and dose to organs. Prospective multi-institutional trials are required to elucidate this matter further. However, as various recent surveys across the world indicate, the heterogeneity of 2D TBI practices, inaccurate dose calculation and dosimetry, and differences in reporting across institutions makes conducting these multi-institutional studies of TBI challenging. Technological advancements in radiotherapy planning and delivery are prompting a transition to modern intensity modulated techniques such as Volumetric Modulated Arc Therapy (VMAT) TBI and helical TomoTherapy TBI, which can better spare normal organs and potentially reduce radiotherapy-related toxicities without compromising TBI effectiveness. This review discusses the present developments and outcomes and toxicity for modern TBI techniques as well as total marrow irradiation (TMI), and total marrow and lymphoid irradiation (TMLI).
Lymphoma in elderly patients has unique treatment challenges due to baseline co-morbidities, nutrition status, impairment in functional capacities and fitness. While geriatric-specific assessment can be used to tailor tr...Lymphoma in elderly patients has unique treatment challenges due to baseline co-morbidities, nutrition status, impairment in functional capacities and fitness. While geriatric-specific assessment can be used to tailor treatment decisions, lack of adequate representation of elderly patients in lymphoma clinical trials impairs generalizability. Radiation treatment has traditionally been associated with high response and local control for lymphomas. The volume and dose of radiation in lymphomas has gradually decreased over the decades, which has led to improved compliance and lower toxicities. The use of radiation in Hodgkin and aggressive B-cell non-Hodgkin lymphomas has allowed for reduction in the number systemic therapy cycles, which is important in elderly patients who may be at high risk for treatment-related adverse events. Current strategies include a risk-adapted approach with minimal chemo-immunotherapy followed by radiation treatment, with dose adapted by response. Here, we provide a review of the literature regarding the role of radiation in the management of elderly patients with lymphoma, especially in follicular lymphoma, diffuse large cell lymphoma and Hodgkin lymphoma.
Hematologic cancers in pediatric, adolescent, and young adult populations include a diverse spectrum of malignancies. The cornerstone of treatment is multiagent chemotherapy. While radiation therapy (RT) is highly effect...Hematologic cancers in pediatric, adolescent, and young adult populations include a diverse spectrum of malignancies. The cornerstone of treatment is multiagent chemotherapy. While radiation therapy (RT) is highly effective and played a pivotal role historically, its use has evolved. In classic HL, advancements in systemic therapy have allowed for reduced RT volumes and doses and careful patient selection. Similarly, NLPHL management has shifted toward observation after complete resection, or limited chemotherapy after incomplete resection with RT used only for partially responding disease sites. In primary mediastinal B-cell lymphoma, the role of RT is an area of active study, and treatment with chemotherapy alone has shown promise in adults. Frontline treatment of diffuse large B-cell lymphoma and Burkitt lymphoma relies on chemotherapy; evidence do not support a role for consolidative RT. In leukemia, the use of prophylactic cranial and testicular RT is declining in the setting of modern chemotherapy regimens. RT may play an important role in the salvage of relapsed/refractory lymphomas and leukemias. In addition, palliative RT is often integral to symptom relief and function preservation. Future research aims to refine risk stratification, personalize treatment approaches, and incorporate novel therapies to maintain or improve oncologic outcomes while mitigating late effects.
Immune checkpoint inhibitors have transformed the future management of classic Hodgkin lymphoma (CHL) in the frontline and salvage settings. Both nivolumab and pembrolizumab have high efficacy in CHL allowing for reducti...Immune checkpoint inhibitors have transformed the future management of classic Hodgkin lymphoma (CHL) in the frontline and salvage settings. Both nivolumab and pembrolizumab have high efficacy in CHL allowing for reduction of chemotherapy and possibly the use of radiotherapy based on short-term follow-up. In this review article, we highlight recent trials enrolling patients with relapse and refractory classic Hodgkin lymphoma receiving monotherapy with PD-1 inhibitors as well as PD-1 and chemotherapy regimens. We also highlight frontline trials utilizing PD-1 inhibitors with chemotherapy with or without radiotherapy. Collectively, the role for radiotherapy in the frontline or salvage setting will become more defined with long-term follow-up of completed studies and results generated from future studies.
Radiotherapy has a long history in the treatment of lymphoma and leukemia, in which late toxicity outcomes have motivated current goals to improve how radiotherapy is delivered. Contemporary advanced radiotherapy techniq...Radiotherapy has a long history in the treatment of lymphoma and leukemia, in which late toxicity outcomes have motivated current goals to improve how radiotherapy is delivered. Contemporary advanced radiotherapy techniques, including intensity modulated radiation therapy (IMRT), proton therapy, deep inspiration breath hold (DIBH), aim to reduce the risk of cardiac morbidity and second cancers caused by radiotherapy while maintaining local control. We use treatment of mediastinal and gastric lymphomas to introduce how modern techniques are chosen for optimal dose delivery, followed by an anatomic site-specific discussion of testicular, bone, and central nervous system disease.
Radiation therapy (RT) is an important modality in the modern management of lymphoma. RT has long been recognized as a cause of late toxicity in lymphoma survivors, including serious morbidity and increased mortality fro...Radiation therapy (RT) is an important modality in the modern management of lymphoma. RT has long been recognized as a cause of late toxicity in lymphoma survivors, including serious morbidity and increased mortality from second cancers and cardiovascular disease. Many studies have quantified the relationships between radiation dose to normal tissues and the risk of late toxicities. These relationships offer the opportunity to estimate future risks for patients on an individual basis. This knowledge has the potential to effect up-front management decisions regarding the use of RT, optimize radiotherapy planning for treatment, guide the evolution of future RT technologies and identify past and future patients whose risk of late toxicity is sufficient to warrant specific screening and surveillance strategies. Despite these potential applications the challenges around translating between radiation dose and accurate predictions of late toxicities are many and substantial. This article summarizes the current state of knowledge, the inherent challenges and possible directions for future research to address this area.
The role of radiotherapy in the treatment of lymphoma is rapidly evolving. The development of modern systemic therapies and the adoption of FDG-PET-scanning as metabolic prognosticators are leading to a process of refine...The role of radiotherapy in the treatment of lymphoma is rapidly evolving. The development of modern systemic therapies and the adoption of FDG-PET-scanning as metabolic prognosticators are leading to a process of refinement of the treatment regimens. In this scenario, radiotherapy utilization is decreasing in several settings, including lower risk patients, to prevent the risk of long-term complications. Over the last decade, the most relevant changes in the treatment landscape are evident for advanced stage Hodgkin lymphoma and diffuse large B cell lymphoma. The main purpose of this paper is to review radiotherapy indications in these settings, to highlight pros and cons of a PET-guided strategy for radiotherapy recommendations, and to introduce future perspectives on the combination of radiotherapy and modern systemic therapies in both frontline and relapsed setting of advanced stage Hodgkin and diffuse large B cell lymphomas.
Semin Radiat Oncol
· 2025 Jan · PMID 39672637
·
Full text
The contemporary landscape of systemic therapy options for hematologic malignancies involving the central nervous system (CNS-HM) is rapidly evolving; a key question is how radiotherapy (RT) can be optimally integrated t...The contemporary landscape of systemic therapy options for hematologic malignancies involving the central nervous system (CNS-HM) is rapidly evolving; a key question is how radiotherapy (RT) can be optimally integrated to improve patient outcomes. Historically, use of RT to treat CNS-HM was defined by broad fields and high doses. While effective, this approach raised concerns of potential neurotoxicity which significantly decreased RT utilization. RT was replaced by high-dose, CNS-penetrant, systemic therapies that offered durable control with lower perceived neurotoxic risk. But, as the therapeutic toolbox for CNS-HM expands, so too does the complexity and diversity of potential clinical scenarios where RT should be considered. In this review, we describe both well-established and emerging opportunities for RT integration, emphasizing how dose selection and field design could balance neurotoxicity risk and disease control. We propose an anatomical framework that captures the diverse utilization of RT for CNS-HM and serves as a practical guide for RT volume and dose design.
Cutaneous T-cell lymphomas (CTCL) are a rare collection of diseases, frequently associated with diagnostic challenges and complex management dilemmas. The multidisciplinary team is vital for accurate clinico-pathological...Cutaneous T-cell lymphomas (CTCL) are a rare collection of diseases, frequently associated with diagnostic challenges and complex management dilemmas. The multidisciplinary team is vital for accurate clinico-pathological diagnoses and for collaborative therapeutic decisions throughout the management journey, which frequently involves multiple lines of therapy. Radiotherapy (RT) is a highly effective skin-directed therapy for CTCL, commonly delivered as localised fields or as total skin electron beam therapy (TSEBT). Mycosis fungoides (MF) is the most common of the CTCL, and patients typically experience high rates of morbidity and long natural histories of relapse and progression. Patients with MF typically present with incurable disease; in these patients, RT has an established role in symptom- and disease-control, achieving excellent response rates and proven therapeutic benefits. The role of RT continues to evolve, with modern practices favouring lower doses to reduce toxicity risks and allow for re-irradiation. Less commonly, there are situations where RT has an integral role in the potential cure of patients with MF: firstly, in the setting of unilesional MF where localised RT alone may be curative, and secondly, in the setting of preconditioning prior to curative-intent allogeneic hematopoietic stem cell transplant for patients with advanced MF/Sezary syndrome, where conventional-dose TSEBT is indicated as the most effective single agent for maximal debulking of skin disease. Radiotherapy also has an important role in the management of the less common CTCL, including the curative treatment of localised primary cutaneous anaplastic large cell lymphoma. Despite proven efficacy and quality of life benefits, disparity exists in access to RT and TSEBT. World-wide, stronger multidisciplinary collaborations and greater patient advocacy are required to increase access to RT and improve equity of care for our patients with CTCL.
Palliative RT is an effective tool in management and treatment of patients with hematologic malignancies. Even relatively low doses of palliative RT can quickly and effectively relieve pain and other symptoms impairing q...Palliative RT is an effective tool in management and treatment of patients with hematologic malignancies. Even relatively low doses of palliative RT can quickly and effectively relieve pain and other symptoms impairing quality of life and function. As so many diseases are represented by the umbrella term, "hematologic malignancies," and each disease has its own natural history and prognosis, the indications for palliative RT are heterogeneous. The following review provides a discussion of when palliative RT should be considered, as well as data-supported dose/fractionation schemes, for non-cutaneous lymphomas and leukemias. It also offers a suggested approach to the patient with a hematologic malignancy requiring palliative RT.
Grover S, Court L, Amoo-Mitchual S
… +28 more, Longo J, Rodin D, Scott AA, Lievens Y, Yap ML, Abdel-Wahab M, Lee P, Harsdorf E, Khader J, Jia X, Dosanjh M, Elzawawy A, Ige T, Pomper M, Pistenmaa D, Hardenbergh P, Petereit DG, Sargent M, Cina K, Li B, Anacak Y, Mayo C, Prattipati S, Lasebikan N, Rendle K, O'Brien D, Wendling E, Coleman CN
There has long existed a substantial disparity in access to radiotherapy globally. This issue has only been exacerbated as the growing disparity of cancer incidence between high-income countries (HIC) and low and middle-...There has long existed a substantial disparity in access to radiotherapy globally. This issue has only been exacerbated as the growing disparity of cancer incidence between high-income countries (HIC) and low and middle-income countries (LMICs) widens, with a pronounced increase in cancer cases in LMICs. Even within HICs, iniquities within local communities may lead to a lack of access to care. Due to these trends, it is imperative to find solutions to narrow global disparities. This requires the engagement of a diverse cohort of stakeholders, including working professionals, non-governmental organizations, nonprofits, professional societies, academic and training institutions, and industry. This review brings together a diverse group of experts to highlight critical areas that could help reduce the current global disparities in radiation oncology. Advancements in technology and treatment, such as artificial intelligence, brachytherapy, hypofractionation, and digital networks, in combination with implementation science and novel funding mechanisms, offer means for increasing access to care and education globally. Common themes across sections reveal how utilizing these new innovations and strengthening collaborative efforts among stakeholders can help improve access to care globally while setting the framework for the next generation of innovations.
Data demonstrates that hypofractionation is increasingly utilized based on evidence-based guidelines. The outdated Medicare fee-for-service approach penalizes radiation oncology (RO) practices from adopting hypofractiona...Data demonstrates that hypofractionation is increasingly utilized based on evidence-based guidelines. The outdated Medicare fee-for-service approach penalizes radiation oncology (RO) practices from adopting hypofractionation, even as many patients benefit. To address the flawed fee-for-service payment system, which rewards volume over value, ASTRO introduced the Radiation Oncology Case Rate (ROCR) Value-Based Payment Program. ROCR shifts payment for RO services from fee-for-service to payment per patient or per episode. To address disparities, ROCR provides an evidence-based approach through the Health Equity Achievement in Radiation Therapy (HEART) initiative, providing transportation assistance payment for the underserved. Additionally, ROCR allows practices sufficient capital to maintain existing equipment and invest in new technology. This increases patient access to technological advancements allowing for more efficient, targeted, and personalized care with improved patient outcomes at a lower overall cost.
Telemedicine allows providers and patients to communicate without being in the same room through video platforms or telephone. Like the increased use of telework for businesses, telemedicine exploded during the pandemic....Telemedicine allows providers and patients to communicate without being in the same room through video platforms or telephone. Like the increased use of telework for businesses, telemedicine exploded during the pandemic. While many workplaces and clinics have returned to some level of in-person interactions, the convenience and comfort have given telemedicine staying power. Patients can be seen from the comfort of their homes; family members can join from the same or a different location. Driving, obtaining childcare, or taking time off from work is unnecessary. Pediatric patients' parents can pull them into the conversation at appropriate times and avoid the awkwardness of having them leave for portions of the discussion. Because virtual visits are more efficient for everyone, they can often be scheduled sooner than an in-person visit. While not every visit can be done without the patient physically with the provider, many can. This is particularly true for cancer patients, who often have several visits with multiple providers. For immunocompromised patients, there is an added benefit of avoiding exposure from travel and a hospital visit. Oncology and radiation oncology practices have widely adopted telemedicine. While legal and logistical barriers exist in some areas of the world, these are sure to be resolved to make this medicine feasible for all in the modern era.