Radiotherapy for the treatment of cancer is undergoing an evolution, shifting to the use of heavier ion species. For a plethora of malignancies, current radiotherapy using photons or protons yields marginal benefits in local control and survival. One hypothesis is that these malignancies have acquired, or are inherently radioresistant to low LET radiation. In the last decade, carbon ion radiotherapy facilities have slowly been constructed in Europe and Asia, demonstrating favorable results for many of the malignancies that do poorly with conventional radiotherapy. However, from a radiobiological perspective, much of how this modality works in overcoming radioresistance, and extending local control and survival are not yet fully understood. In this review, we will explain from a radiobiological perspective how carbon ion radiotherapy can overcome the classical and recently postulated contributors of radioresistance (α/β ratio, hypoxia, cell proliferation, the tumor microenvironment and metabolism, and cancer stem cells). Furthermore, we will make recommendations on the important factors to consider, such as anatomical location, in the future design and implementation of clinical trials. With the existing data available we believe that the expansion of carbon ion facilities into the United States is warranted.
Background and Purpose Various radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN. Materials and Methods Initial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy. Contouring was performed on both CTs, and plans (n=40 plans) and dose volume histograms were generated. Results The mean GTV volume decreased 53.4% with re-simulation. All plans provided comparable PTV coverage. Compared with IMRT, adaptive IMRT significantly reduced the maximum dose to the mandible (p=0.020) and mean doses to the contralateral parotid gland (p=0.049) and larynx (p=0.049). Compared with IMRT and adaptive IMRT, IMPT significantly lower the maximum doses to the spinal cord (p<0.002 for both) and brainstem (p<0.002 for both) and mean doses to the larynx (p<0.002 for both) and ipsilateral (p=0.004 IMRT, p=0.050 adaptive) and contralateral (p<0.002 IMRT, p=0.010 adaptive) parotid glands. Adaptive IMPT significantly reduced doses to all critical structures compared with IMRT and adaptive IMRT and several critical structures compared with non-adaptive IMPT. Conclusions Although adaptive IMRT reduced dose to several normal structures compared with standard IMRT, non-adaptive proton therapy had a more favorable dosimetric profile than IMRT or adaptive IMRT and may obviate the need for adaptive planning. Protons allowed significant sparing of the spinal cord, parotid glands, larynx, and brainstem and should be considered for SCCHN to decrease normal tissue toxicity while still providing optimal tumor coverage.
This study described, developed, and tested new processing methods for reducing inaccuracies in absolute dose determination due to inhomogeneities within the film and from scanning. This study found better performance using optimized multichannel following averaging of all color channels. Combining the channel ratios in a hybrid approach also achieved high performance. Averaging the test films reduced temporal noise that severely degraded the blue channel. This methodology avoided using cumbersome, registered correction matrices. Novel registration and digital rotation of CT images enabled quantitative testing and helped improve contact between the radiochromic film and phantom.
Improving diagnosis and treatment depends on clinical monitoring and computing. Clinical decision support systems (CDSS) have been in existence for over 50 years. While the literature points to positive impacts on quality and patient safety, outcomes, and the avoidance of medical errors, technical and regulatory challenges continue to retard their rate of integration into clinical care processes and thus delay the refinement of diagnoses towards personalized care. We conducted a systematic review of pertinent articles in the MEDLINE, US Department of Health and Human Services, Agency for Health Research and Quality, and US Food and Drug Administration databases, using a Boolean approach to combine terms germane to the discussion (clinical decision support, tools, systems, critical care, trauma, outcome, cost savings, NSQIP, APACHE, SOFA, ICU, and diagnostics). References were selected on the basis of both temporal and thematic relevance, and subsequently aggregated around four distinct themes: the uses of CDSS in the critical and surgical care settings, clinical insertion challenges, utilization leading to cost-savings, and regulatory concerns. Precision diagnosis is the accurate and timely explanation of each patient's health problem and further requires communication of that explanation to patients and surrogate decision-makers. Both accuracy and timeliness are essential to critical care, yet computed decision support systems (CDSS) are scarce. The limitation arises from the technical complexity associated with integrating and filtering large data sets from diverse sources. Provider mistrust and resistance coupled with the absence of clear guidance from regulatory bodies further retard acceptance of CDSS. While challenges to develop and deploy CDSS are substantial, the clinical, quality, and economic impacts warrant the effort, especially in disciplines requiring complex decision-making, such as critical and surgical care. Improving diagnosis in health care requires accumulation, validation and transformation of data into actionable information. The aggregate of those processes-CDSS-is currently primitive. Despite technical and regulatory challenges, the apparent clinical and economic utilities of CDSS must lead to greater engagement. These tools play the key role in realizing the vision of a more 'personalized medicine', one characterized by individualized precision diagnosis rather than population-based risk-stratification.
Purpose-Photon radiotherapy has been standard adjuvant treatment for stage I seminoma. Single dose carboplatin and observation have emerged as alternative options due to concerns of acute toxicities and secondary malignancies from radiation. In this IRB-approved study, we compare photon and proton radiotherapy for stage I seminoma and predict rates of excess secondary malignancies for both treatment modalities.Methods and Material-CT images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapy. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors.Results-Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues except the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119cGy vs. 768cGy, p<0.0001). Significantly more excess secondary cancers per 10,000 patients/yr were predicted with photons compared with protons for the stomach (4.11; 95% CI=3.22-5.01), large bowel (0.81; CI=0.39-1.01), and bladder (0.03; CI=0.01-0.58), while no difference was demonstrated for the pancreas (0.02; CI=−0.01-0.06). Conflict of Interest: nonePublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptInt J Radiat Oncol Biol Phys. Author manuscript; available in PMC 2013 January 1. Conclusions-For patients with stage I seminoma, proton therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients with a life expectancy of 40 years from the time of radiation treated with protons instead of photons. Protons also allowed significant sparing of most critical structures examined and warrant further study for patients with seminoma to decrease radiation-induced toxicity.
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