Adiation Therapy Research Articles

Reappraisal of the role of radiation therapy in lymphoma treatment

AbstractRadiation therapy (RT) for lymphomas has improved dramatically with modern imaging and treatment techniques, encompassing only the necessary volume with minimal doses to normal structures. Prescribed radiation doses are reduced, and fractionation schedules are under revision. With effective systemic treatment only initial macroscopic disease is irradiated. With no or less effective systemic treatment, possible microscopic disease is also included. Risks of long‐term side effects of RT have diminished dramatically and should be weighed against risks from more systemic treatment or increased risk of relapse. Lymphoma patients are often elderly, they tolerate modern limited RT very well. Lymphomas refractory to systemic treatments often remain radioresponsive, and brief, mild RT may offer effective palliation. New roles for RT are emerging with immune therapies. RT for “bridging,” keeping the lymphoma under control while waiting for immune therapy, is well established. Enhancement of the immune response to lymphomas, so‐called “priming,” is being intensively researched.

Experience with stereotactic r adiation therapy for liver oligometastases of colorectal cancer

Introduction: The problem of treating patients with unresectable liver metastases of colon cancer is currently far f rom being solved. One possible approach is the use of stereotactic body radiotherapy.The purpose of this study was to evaluate the immediate and long-term results of stereotactic radiotherapy in patients with colorectal cancer and oligometastatic liver metastases.Methods: This study was designed as a retro-prospective, open-label, controlled, non-randomized clinical trial. We assessed one-year local control, one-year overall survival, progression-free survival, and toxicity in 60 patients with oligometastatic liver disease from colorectal cancer who underwent stereotactic body radiotherapy, with median dose of 54 Gy.Results: The median follow-up was 20,1 months. One-year local control (LC) was 73,7 % (95 % CI = 62,7–86,6 %). Oneyear overall survival (OS) was 92,8 % (95 % CI = 86,3–99,9 %), one-year progression-free survival (PFS) was 31,3 % (95 % CI = 21,1–46,4 %) with a median of 8,1 months. Grade ≥ 3 toxicity was not noted. No cases of radiation-induced liver failure were observed. Radiation dose (HR = 0.88, 95 % CI = 0.81–0.95, p = 0.00087), metastasis size (HR = 1.51, 95 % CI = 1.07–2.12, p = 0.01858) and their number (HR = 1.8, 95 % CI = 1.01–3.22, p = 0.04669) are significant risk factors for LC. Metastasis size > 3 cm is a significant risk factor for LC (HR = 5.5, 95 % CI = 1.7–17.9, p = 0.005) and OS (HR = 3.8, 95 % CI = 1.3–11.7, p = 0.02).Conclusion: Stereotactic body radiotherapy is an effective and safe method of providing local control of oligometastatic liver metastases in colorectal cancer as part of a combined treatment approach. Further studies are required to individualize the indications for this treatment method.

Imaging Features of Postradiotherapy Changes in Head and Neck Cancers.

Radiation therapy is the mainstay in the treatment of head and neck cancers, in addition to surgery and chemotherapy. Expected radiotherapy changes evolving over time may be confused with recurrent tumor. Conversely, even residual or recurrent tumor in the setting of postradiotherapy changes may be difficult to identify clinically or even by radiological imaging. Therefore, it is important to be familiar with the temporal evolution of these changes. The purpose of this pictorial essay is thus to illustrate distinctly the expected radiotherapy changes and radiotherapy-related complications in the head and neck region and to differentiate them from tumor recurrence on routine cross-sectional imaging techniques (computed tomography and magnetic resonance imaging).

Supportive care for toxicities in children undergoing radiation therapy.

Radiation therapy (RT) is an integral part of the management of many pediatric tumors; however, it is associated with both acute and permanent adverse events that can significantly impact a child's quality of life, lead to treatment delays, and potentially affect outcomes of cancer therapy. Prevention, early detection, and optimal management of these adverse effects will help reduce their impact on the patients' quality of life and overall well-being. Unfortunately, there has not been a coordinated effort to study the etiology, evaluate risk factors, and explore novel treatments for these conditions. Studies of supportive care for children undergoing RT are often small and uncontrolled. This review will focus on the impact of irradiation on the different organ systems and their current management. Further studies are required to improve our understanding of the contributing factors and explore novel treatment options for these adverse effects and to enable children and their families to better cope with some of the unavoidable toxicities following multimodality therapy.

Palliative radiation therapy for children with cancer.

Radiation therapy (RT) is often used as a palliative treatment for children with recurrent malignant disease to ameliorate or prevent symptoms. However, no guidelines exist regarding the clinical indications or dose fractionation for palliative RT. The goal of this report is to provide guidelines for the use of palliative RT in children with cancer. In this guideline, appropriate indications for palliative RT, recommended dose-fractionation schedules, relevant toxicities, and avenues for future research are explored. RT is an effective palliative treatment for bone, brain, liver, lung, abdominopelvic and head-and-neck metastases, spinal cord compression, superior vena cava syndrome, and bleeding. Single-fraction regimens (8Gy in one fraction) for children with short life expectancy are recommended for simple, uncomplicated bone metastases and can be considered for some patients with lung or liver metastases. A short, hypofractionated regimen (20Gy in five fractions) may be used for other indications to minimize overall burden of therapy. There are little data supporting use of more prolonged fractionation regimens, though they may be considered for patients with very good performance status. Future research should focus on response and outcomes data collection, and to rigorously evaluate the role of stereotactic body RT in well-designed, prospective studies.

An automated treatment planning strategy for highly noncoplanar radiotherapy arc trajectories

AbstractRadiation therapy is a technology‐driven cancer treatment modality that has experienced significant advances over the last decades, due to multidisciplinary contributions that include engineering and computing. Recent technological developments allow the use of noncoplanar volumetric modulated arc therapy (VMAT), one of the most recent photon treatment techniques, in clinical practice. In this work, an automated noncoplanar arc trajectory optimization framework designed in two modular phases is presented. First, a noncoplanar beam angle optimization algorithm is used to obtain a set of noncoplanar irradiation directions. Then, anchored in these directions, an optimization strategy is proposed to compute an optimal arc trajectory. The computational experiments considered a pool of twelve difficult head‐and‐neck tumor cases. It was possible to observe that, for some of these cases, the optimized noncoplanar arc trajectories led to significant treatment planning quality improvements, when compared with coplanar VMAT treatment plans. Although these experiments were done in a research environment treatment planning software (matRad), the conclusions can be of interest for a clinical setting: automated procedures can simplify the current treatment workflow, produce high‐quality treatment plans, making better use of human resources and allowing for unbiased comparisons between different treatment techniques.

Osteoradionecrosis of the Midface and Mandible: Pathogenesis and Management.

Radiation therapy is an important and commonly used treatment modality for head and neck cancers. Osteoradionecrosis (ORN) is a potential debilitating complication of treatment, which most commonly affects the mandible. Management strategies are tailored to the severity of disease. Medical management including oral rinses, irrigations, antibiotics, and pharmacological treatments is viable for mild-to-moderate ORN. More severe disease is best addressed with a combination of medical management and surgical intervention aimed at aggressively removing devitalized tissue until bleeding bone is encountered and reconstructing the soft tissue and bone defect. Reconstruction with either regional vascularized flaps or vascularized osteocutaneous free flaps in case of larger full-thickness bone defects (greater than 6 cm) or anterior mandible (medial to mental foramen) is most appropriate. Maxillary ORN complications can present with a wide range of functional problems and facial disfigurement. Life-threatening and time-sensitive problems should be treated first, such as skull base bone coverage or correction of severe ectropion, to avoid blindness from exposure keratopathy. Then, less time-sensitive issues can be addressed next, such as nasal obstruction, velopharyngeal insufficiency, and chronic tearing. It may require a combination of specialists from different disciplines to address various issues that can arise from maxillary ORN.

Radiation Necrosis of the Lateral Skull Base and Temporal Bone.

Radiation therapy plays a critical role in the treatment of malignancies involving the head and neck. Although the therapeutic effects of ionizing radiation are achieved, normal tissues are also susceptible to injury and significant long-term sequelae. Osteoradionecrosis of the temporal bone (ORNTB) is among the many complications that can arise after therapy. ORNTB is a debilitating and potentially lethal condition that continues to challenge patients and treating physicians. Herein, we review the pathophysiology, presentation, work-up, and management of ORNTB.

Management and Surveillance of Short- and Long-Term Sequelae of Radiation Therapy for the Treatment of Pediatric Brain Tumors

AbstractRadiation therapy (RT) is a mainstay for the treatment of pediatric brain tumors. As improvements in and sophistication of this modality continue to increase the survival of patients, the long-term sequelae of RT pose significant challenges in the clinical management of this patient population as they transition into adulthood. In this special edition, we review the short- and long-term effects of RT for the treatment of pediatric brain tumors and the necessary surveillance required for follow-up.

Radiation‐activated prosurvival signaling pathways in cancer cells

AbstractRadiation therapy is a standard treatment for local disease control of solid tumors. Although radiation therapy has significantly improved the overall survival and quality of life of cancer patients, its efficacy has been limited by the development of radiation resistance and the presence of residual disease after therapy, leading to cancer recurrence. Radiation induces cytotoxicity in cancer cells, mainly by causing DNA damage. However, concurrently radiation can also activate multiple protective signaling pathways, such as ataxia telangiectasia mutated/ataxia telangiectasia mutated and Rad3‐related protein, phosphoinositide‐3‐kinase/protein kinase B, extracellular signal‐regulated kinase, and nuclear factor‐κB, which promote cell cycle checkpoint activation, leading to cell cycle arrest/DNA repair and inhibition of apoptosis. Conjointly, these signaling pathways protect cancer cells by reducing the magnitude of radiation‐induced cytotoxicity and promoting radioresistance of cancer cells. Thus, targeting these prosurvival pathways could have great potential for sensitizing cancer cells to radiation therapy. In the present review, we summarize the current literature on the radiation‐activated prosurvival signaling pathways that promote radioresistance.

State‐of‐the‐Art Report: Visual Computing in Radiation Therapy Planning

AbstractRadiation therapy (RT) is one of the major curative approaches for cancer. It is a complex and risky treatment approach, which requires precise planning, prior to the administration of the treatment. Visual Computing (VC) is a fundamental component of RT planning, providing solutions in all parts of the process—from imaging to delivery. Despite the significant technological advancements of RT over the last decades, there are still many challenges to address. This survey provides an overview of the compound planning process of RT, and of the ways that VC has supported RT in all its facets. The RT planning process is described to enable a basic understanding in the involved data, users and workflow steps. A systematic categorization and an extensive analysis of existing literature in the joint VC/RT research is presented, covering the entire planning process. The survey concludes with a discussion on lessons learnt, current status, open challenges, and future directions in VC/RT research.

RTHP-01. SPECTROSCOPIC MRI PREDICTS RECURRENCE PATTERNS IN GLIOBLASTOMA

AbstractRadiation therapy (RT) targeted by conventional MRI may not fully identify the tumor profile of (GBM), which may in part account for high recurrence rates. Identifying the extent of GBM margins remains a challenging task due to the infiltrative nature of these tumors and limitations in current standard imaging methods. Multiple studies have demonstrated that MR spectroscopic imaging, or spectroscopic MRI (sMRI), can detect areas of infiltrating tumor with a high degree of sensitivity, and could be an essential tool in targeting tumor margins. sMRI enables the identification of non-enhancing, infiltrating cells that are marked by increased Choline/N-Acetylaspartate ratio (Cho/NAA), including regions undetected by standard MRI and therefore left untreated. sMRI shows considerable promise for improving the efficacy of RT and may delay recurrence. In this study, we correlated pre-treatment sMRI metabolite maps with recurrence patterns to validate that sMRI could provide coverage for untreated regions that later recurred, and provide support for its adjunctive use in tumor contouring for RT planning. In an ongoing NCI-funded trial (U01CA172027), metabolite and their ratio maps were obtained pre-chemoradiation and normalized to the patient’s normal-appearing contralateral white matter (NAWM) and then compared to contrast-enhancing recurrence patterns with at least 6 months follow-up. A Cho/NAA ratio of twice the NAWM mean was used to identify regions of potential infiltration in our patients, and the resulting planning target volumes were compared with actual treated target volumes based on conventional MRI. For 9 out of 11 cases, the addition of sMRI data expanded RT volumes to better encompass regions of tumor recurrence, which were not completely covered by the CTV60. Thus, RT planning for GBMs augmented by sMRI could reduce recurrence rates. A multi-institutional clinical trial has been initiated to prospectively assess potential for sMRI to guide RT and assess treatment response (R01CA214557).

ID2011 Potential strategies to improve Temozolomide/ radiation therapy of malignant gliomas by targeting glycolytic energy metabolism

The current standard treatment of Malignant Gliomas includes surgery, followed by Temozolomide (TMZ) - Radiotherapy. It leads to increased survival as compared to radiotherapy alone. However, haematological toxicities are also increased by the combination treatments. Therefore, it is important to carry out further preclinical studies, to develop more effective treatment for these tumors. 2-Deoxy-D-Glucose (2-DG), an inhibitor of glycolytic energy metabolism, has been shown earlier to differentially inhibit repair processes, growth and survival of cancer cells. It has been tolerated very well in combination with radiotherapy in clinical trials on Malignant Gliomas. In this study, we investigated the effects of combination of clinically relevant concentrations of 2-DG (0.5mM and 1mM) and TMZ (2µM and 5µM) ± Radiation (1Gy) on cell proliferation, total cellular damage (TCD) and colony formation in an established Glioblastoma cell line (U251MG), and primary cultures derived from malignant glioma tumor pieces. The monolayer cultures were grown on cover slips and stained with Acridine Orange (0.002%) after drug treatments and irradiation, for the study of cellular damage and death. Exponentially growing cells were exposed to drugs and Gamma irradiation. Drugs were removed 4 hrs after irradiation and cultures were processed for different assays of cell death and damage. Our results showed that combination of 2-DG with TMZ±Radiation significantly inhibited the cell proliferation up to 6 days. The TCD was significantly increased by the combination of drugs in primary as well as in established cell line. Cell proliferation as measured by MTT assay showed that drugs ± radiation significantly reduced proliferation response. Cell survival inhibition after combination of TMZ+2-DG+Gamma (2µM+0.5mM+1Gy) showed more than additive effects. These results suggest that targeting glycolytic energy metabolism by agents such as 2-DG can enhance the efficacy of TMZ+Radiation Therapy for Malignant Gliomas, without increasing toxic side effects

Preclinical immunoPET/CT imaging using Zr-89-labeled anti-PD-L1 monoclonal antibody for assessing radiation-induced PD-L1 upregulation in head and neck cancer and melanoma

ABSTRACTRadiation therapy (RT) can induce upregulation of programmed death ligand 1 (PD-L1) on tumor cells or myeloid cells, which may affect response to PD-1-based immunotherapy. PD-L1 upregulation during RT is a dynamic process that has been difficult to monitor during treatment. The aim of this study was to evaluate the RT-induced PD-L1 upregulation in the tumor and its microenvironment using immunoPET/CT imaging of two syngeneic murine tumor models (HPV+ head and neck squamous cell carcinoma (HNSCC) or B16F10 melanoma). Tumors were established in two locations per mouse (neck and flank), and fractionated RT (2 Gy × 4 or 2 Gy × 10) was delivered only to the neck tumor, alone or during anti-PD-1 mAb immunotherapy. PD-L1 expression was measured by PET/CT imaging using Zr-89 labeled anti-mouse PD-L1 mAb, and results were validated by flow cytometry. PET/CT imaging demonstrated significantly increased tracer uptake in irradiated neck tumors compared with non-irradiated flank tumors. Ex vivo analysis by biodistribution and flow cytometry validated PD-L1 upregulation specifically in irradiated tumors. In the HNSCC model, RT-induced PD-L1 upregulation was only observed after 2 Gy × 10 fractionated RT, while in the B16F10 model upregulation of PD-L1 occurred after 2 Gy × 4 fractionated RT. Fractionated RT, but not anti-PD-1 therapy, upregulated PD-L1 expression on tumor and infiltrating inflammatory cells in murine models, which could be non-invasively monitored by immunoPET/CT imaging using Zr-89 labeled anti-mouse PD-L1 mAb, and differentially identified anti-PD-1 responsive as well as selectively irradiated tumors in vivo.

Techniques to Analyze the Effects of Radiation Therapy on Enamel and Dentin - A Review

AbstractRadiation therapy is a most common source in the treatment of Head and neck cancers. The therapy has a positive outcome in curing patients out of danger at an effective rate. But there are few major and minor side effects of the treatment which will possibly hinder the quality of life. One such major concern followed with the therapy is Radiation related caries. Radiation is known to damage the tissues of the teeth making it more susceptible for caries. Hence this review article details on techniques that is being used to test the mechanical and morphological properties of the teeth. The changes observed in these tissues after radiation treatment will enable us to understand the causes for caries. therefore further research in this field is necessary to develop strategies that will probably prevent radiation caries in future days.

Swallowing after non-surgical treatment (radiation therapy / radiochemotherapy protocol) of laryngeal cancer

AbstractRadiation therapy and radiochemotherapy protocols can cause swallowing difficulties.Aim: To evaluate swallowing in patients undergoing radiation therapy and radiochemotherapy protocol only for the treatment of laryngeal tumors.Methods: A prospective study of 20 patients, with a mean age of 62 years, at the end of oncological therapy. Six patients (30%) underwent radiation therapy, and 14 patients (70%) underwent combined therapy. The mean time between treatment and an evaluation of swallowing was 8.5 months. Videofluoroscopy was done to assess the preparatory, oral and pharyngeal phases of swallowing.Results: All patients had only an oral diet. Normal swallowing was present in only 25% of patients. The swallowing videofluoroscopic examination identified the following changes: bolus formation (85%), bolus ejection (60%), oral cavity stasis (55%), changes in the onset of the pharyngeal phase (100%), decreased laryngeal elevation (65%), and hypopharyngeal stasis (80%). Laryngeal penetration was observed in 25% of the cases; 40% presented tracheal aspiration. The grade of penetration/ aspiration was mild in 60% of cases. Aspiration was silent in 35% of patients. Although 75% of patients had dysphagia, only 25% complained of swallowing difficulties.Conclusion: Patients with laryngeal cancer that underwent radiation therapy/combined treatment can present changes in all swallowing phases, or may be asymptomatic.

Use of double skin paddle for pharyngoesophageal reconstruction using tubed radial forearm free flap

r c econstruction of pharyngeal defects are complex and ely upon advanced microsurgical skill to ensure success. hese can also be compromised by the effect radioherapy necessitating delayed reconstructive surgery to orrect soft tissue stricturing of the pharynx many years ater. We describe how adaptations in flap design can help adeuately reconstruct the pharynx and prevent tension in the adiation treated neck. Following laryngectomy strictures may develop in the harynx or oesophagus and impede bolus passage and voice roduction. This can be related to tight surgical closures, adiation therapy and post-operative infections. Post laryngectomy patients use small valves to create air esonance and tracheoesophageal speech. Tightness here can ffect the patients voice quality and hence directly impact pon their quality of life. Patient A had a total laryngectomy and neck dissection in 006 following which they had radiotherapy and remained isease free. The patient was fitted with a Blom-Singer voice rosthesis for voice reproduction. Over the proceeding 6

A review on radiotherapy hypofractionation schedules for breast cancer treatment

AbstractRadiation therapy is an integral part of management in breast carcinoma treatment. Standard curative schedules of radiotherapy to the breast deliver 25 fractions of 2.0 Gy per day over 5–6 weeks. Considerable recent literature suggests that hypo-fractionation may be advisory in breast cancer. The use of fewer fractions of more than 2 Gy per day (hypo-fractionation) is based on data suggesting that breast carcinoma is more sensitive to fraction size than squamous carcinomas and therefore could have similar fractionation sensitivity to the dose-limiting healthy tissues, including skin, subcutaneous tissues, muscle and ribs. In this article, a review of published studies and currently ongoing trials, which may provide evidence for the use of hypo-fractionated radiotherapy in breast cancer patients, is presented. Also, for all these different hypo-fractionation regimens found in literature, biologically effective dose (BED) values are calculated and compared. Data from studies and randomised trials seem to support the concept that modest hypo-fractionation can be used to treat the whole breast after breast-conserving surgery with similar rates of local control and radiation morbidity as seen with conventional fractionation.

Radiation therapist research in Africa: overcoming the barriers to reap the rewards

AbstractRadiation therapy is recognised throughout the world as an essential modality in the treatment of many malignant diseases. A quality treatment process requires highly competent health care professionals and high-technology equipment. In the majority of countries in Africa there is a desperate need for equipment and skilled therapists and in many countries there is no access to radiation therapy to relieve the suffering of cancer patients. As a region, Africa can therefore be considered as ‘under resourced’ in terms of radiation oncology services. In this context both service and research are challenged by a lack of equipment, poor maintenance, inadequate funding, inconsistent consumable supplies, a scarcity of competent professionals to ensure optimal use of what is available and excessive workload. Africa therefore has many examples of the situation, where low-income countries generally have a poor research infrastructure. Radiation therapist (RTT) research in Africa has to develop where the barriers to research can in most instances be traced back to a lack of resources and any initiatives to overcome these barriers are frequently blocked by the limitations of a resource-poor environment. To locate the discussion on the research environment of RTTs in Africa, barriers to and benefits of research are integrated with brief information under the following headings: the macro environment, the RTT environment and the RTT research environment. The latter includes insights from interviews and discussions covering the following topics: research now, research priorities, research opportunities and strategies for future research.

Tin foil modified electron radiation of the skin of the nose

AbstractRadiation therapy to the skin of the nose for non‐melanoma skin cancer is common in Australia yet presents numerous dosimetric and practical challenges. A tin foil modified electron (TME) radiation technique has been used routinely at Perth Radiation Oncology since 2001. The development of this technique over an extended period involving almost 100 cases is reported and key processes at simulation, planning and treatment delivery are described. A summary of major clinical outcomes is presented for 53 patients treated with TME between 2001 and 2005.