Rachel B. Ger PhD , Lise Wei PhD , Issam El Naqa PhD , Jing Wang PhD
{"title":"The Promise and Future of Radiomics for Personalized Radiotherapy Dosing and Adaptation","authors":"Rachel B. Ger PhD , Lise Wei PhD , Issam El Naqa PhD , Jing Wang PhD","doi":"10.1016/j.semradonc.2023.03.003","DOIUrl":"10.1016/j.semradonc.2023.03.003","url":null,"abstract":"<div><p>Quantitative image analysis, also known as radiomics<span><span><span><span>, aims to analyze large-scale quantitative features extracted from acquired medical images using hand-crafted or machine-engineered feature extraction approaches. Radiomics has great potential for a variety of clinical applications in radiation oncology, an image-rich </span>treatment modality that utilizes </span>computed tomography<span> (CT), magnetic resonance imaging (MRI), and </span></span>positron emission tomography<span> (PET) for treatment planning, dose calculation, and image guidance<span>. A promising application of radiomics is in predicting treatment outcomes after radiotherapy such as local control and treatment-related toxicity using features extracted from pretreatment and on-treatment images. Based on these individualized predictions of treatment outcomes, radiotherapy dose can be sculpted to meet the specific needs and preferences of each patient. Radiomics can aid in tumor characterization for personalized targeting, especially for identifying high-risk regions within a tumor that cannot be easily discerned based on size or intensity alone. Radiomics-based treatment response prediction can aid in developing personalized fractionation and dose adjustments. In order to make radiomics models more applicable across different institutions with varying scanners and patient populations, further efforts are needed to harmonize and standardize the acquisition protocols by minimizing uncertainties within the imaging data.</span></span></span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 252-261"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9691596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radiotherapy Dose in Patients Receiving Immunotherapy","authors":"Kelly J. Fitzgerald, Jonathan D. Schoenfeld","doi":"10.1016/j.semradonc.2023.03.012","DOIUrl":"10.1016/j.semradonc.2023.03.012","url":null,"abstract":"<div><p>There is significant rationale for combining radiation therapy<span><span><span> (RT) and immuno-oncology (IO) agents, but the optimal radiation parameters are unknown. This review summarizes key trials in the RT and IO space with a focus on RT dose. Very low RT doses solely modulate the tumor immune microenvironment, intermediate doses both modulate the tumor immune microenvironment and kill some fraction of tumor cells, and ablative doses eliminate the majority of target tumor cells and also possess immunomodulatory effects. Ablative RT doses may have high toxicity if targets are adjacent to radiosensitive normal organs. The majority of completed trials have been conducted in the setting of </span>metastatic disease and direct RT to a single lesion with the goal of generating systemic antitumor immunity termed the </span>abscopal effect. Unfortunately, reliable generation of an abscopal effect has proved elusive over a range of radiation doses. Newer trials are exploring the effects of delivering RT to all or most sites of metastatic disease, with dose personalization based on the number and location of lesions. Additional directions include testing RT and IO in earlier stages of disease, sometimes in further combination with chemotherapy and surgery, where lower doses of RT may still contribute substantially to pathologic responses.</span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 327-335"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noah Earland , Kevin Chen MD , Nicholas P. Semenkovich MD, PhD , Pradeep S. Chauhan PhD , Jose P. Zevallos MD , Aadel A. Chaudhuri MD, PhD
{"title":"Emerging Roles of Circulating Tumor DNA for Increased Precision and Personalization in Radiation Oncology","authors":"Noah Earland , Kevin Chen MD , Nicholas P. Semenkovich MD, PhD , Pradeep S. Chauhan PhD , Jose P. Zevallos MD , Aadel A. Chaudhuri MD, PhD","doi":"10.1016/j.semradonc.2023.03.004","DOIUrl":"10.1016/j.semradonc.2023.03.004","url":null,"abstract":"<div><p><span>Recent breakthroughs in circulating tumor DNA<span> (ctDNA) technologies present a compelling opportunity to combine this emerging liquid biopsy<span> approach with the field of radiogenomics, the study of how tumor genomics correlate with radiotherapy<span> response and radiotoxicity. Canonically, ctDNA levels reflect metastatic tumor<span> burden, although newer ultrasensitive technologies can be used after curative-intent radiotherapy of localized disease to assess ctDNA for minimal residual disease (MRD) detection or for post-treatment surveillance. Furthermore, several studies have demonstrated the potential utility of ctDNA analysis across various cancer types managed with radiotherapy or </span></span></span></span></span>chemoradiotherapy<span><span>, including sarcoma and cancers of the head and neck, lung, colon, rectum, </span>bladder<span>, and prostate . Additionally, because peripheral blood mononuclear cells<span><span> are routinely collected alongside ctDNA to filter out mutations associated with clonal hematopoiesis, these cells are also available for </span>single nucleotide polymorphism<span> analysis and could potentially be used to detect patients at high risk for radiotoxicity. Lastly, future ctDNA assays will be utilized to better assess locoregional MRD in order to more precisely guide adjuvant radiotherapy after surgery in cases of localized disease, and guide ablative radiotherapy in cases of oligometastatic disease.</span></span></span></span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 262-278"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elham Rahimy, Michael F. Gensheimer, Beth Beadle, Quynh-Thu Le
{"title":"Lessons and Opportunities for Biomarker-Driven Radiation Personalization in Head and Neck Cancer","authors":"Elham Rahimy, Michael F. Gensheimer, Beth Beadle, Quynh-Thu Le","doi":"10.1016/j.semradonc.2023.03.013","DOIUrl":"10.1016/j.semradonc.2023.03.013","url":null,"abstract":"<div><p><span>Head and neck cancer<span> is notoriously challenging to treat in part because it constitutes an anatomically and biologically diverse group of cancers with heterogeneous prognoses. While treatment can be associated with significant late toxicities, recurrence is often difficult to salvage with poor survival rates and functional morbidity.</span></span><span><sup>1</sup></span><sup>,</sup><span><sup>2</sup></span><span><span> Thus, achieving tumor control and cure at the initial diagnosis is the highest priority. Given the differing outcome expectations (even within a specific sub-site like oropharyngeal carcinoma), there has been growing interest in personalizing treatment: de-escalation in selected cancers to decrease the risk of late toxicity without compromising oncologic outcomes, and intensification for more aggressive cancers to improve oncologic outcomes without causing undue toxicity. This risk stratification is increasingly accomplished using biomarkers, which can represent molecular, clinicopathologic, and/or radiologic data. In this review, we will focus on biomarker-driven </span>radiotherapy dose personalization with emphasis on oropharyngeal and nasopharyngeal carcinoma. This radiation personalization is largely performed on the population level by identifying patients with good prognosis via traditional clinicopathologic factors, although there are emerging studies supporting inter-tumor and intra-tumor level personalization via imaging and molecular biomarkers.</span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 336-347"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Philip Sutera MD , Heath Skinner MD, PhD , Matthew Witek MD , Mark Mishra MD , Young Kwok MD , Elai Davicioni PhD , Felix Feng MD , Daniel Song MD , Elizabeth Nichols MD , Phuoc T. Tran MD, PhD , Carmen Bergom MD, PhD
{"title":"Histology Specific Molecular Biomarkers: Ushering in a New Era of Precision Radiation Oncology","authors":"Philip Sutera MD , Heath Skinner MD, PhD , Matthew Witek MD , Mark Mishra MD , Young Kwok MD , Elai Davicioni PhD , Felix Feng MD , Daniel Song MD , Elizabeth Nichols MD , Phuoc T. Tran MD, PhD , Carmen Bergom MD, PhD","doi":"10.1016/j.semradonc.2023.03.001","DOIUrl":"10.1016/j.semradonc.2023.03.001","url":null,"abstract":"<div><p>Histopathology<span><span> and clinical staging have historically formed the backbone for allocation of </span>treatment<span><span><span><span> decisions in oncology. Although this has provided an extremely practical and fruitful approach for decades, it has long been evident that these data alone do not adequately capture the heterogeneity and breadth of disease trajectories experienced by patients. As efficient and affordable DNA and </span>RNA sequencing<span> have become available, the ability to provide precision therapy has become within grasp. This has been realized with systemic oncologic therapy, as targeted therapies have demonstrated immense promise for subsets of patients with oncogene-driver mutations. Further, several studies have evaluated predictive biomarkers for response to systemic therapy within a variety of </span></span>malignancies<span>. Within radiation oncology, the use of genomics/transcriptomics to guide the use, dose, and fractionation of </span></span>radiation therapy is rapidly evolving but still in its infancy. The genomic adjusted radiation dose/radiation sensitivity index is one such early and exciting effort to provide genomically guided radiation dosing with a pan-cancer approach. In addition to this broad method, a histology specific approach to precision radiation therapy is also underway. Herein we review select literature surrounding the use of histology specific, molecular biomarkers to allow for precision radiotherapy with the greatest emphasis on commercially available and prospectively validated biomarkers.</span></span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 232-242"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10446901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Javier F. Torres-Roca , G. Daniel Grass , Jacob G. Scott , Steven A. Eschrich
{"title":"Towards Data Driven RT Prescription: Integrating Genomics into RT Clinical Practice","authors":"Javier F. Torres-Roca , G. Daniel Grass , Jacob G. Scott , Steven A. Eschrich","doi":"10.1016/j.semradonc.2023.03.007","DOIUrl":"10.1016/j.semradonc.2023.03.007","url":null,"abstract":"<div><p><span>The genomic era has significantly changed the practice of clinical oncology<span><span>. The use of genomic-based molecular diagnostics including prognostic </span>genomic signatures<span> and new-generation sequencing has become routine for clinical decisions regarding cytotoxic chemotherapy, targeted agents and </span></span></span>immunotherapy<span>. In contrast, clinical decisions regarding radiation therapy (RT) remain uninformed about the genomic heterogeneity of tumors. In this review, we discuss the clinical opportunity to utilize genomics to optimize RT dose. Although from the technical perspective, RT has been moving towards a data-driven approach, RT prescription dose is still based on a one-size-fits all approach, with most RT dose based on cancer diagnosis and stage. This approach is in direct conflict with the realization that tumors are biologically heterogeneous, and that cancer is not a single disease. Here, we discuss how genomics can be integrated into RT prescription dose, the clinical potential for this approach and how genomic-optimization of RT dose could lead to new understanding of the clinical benefit of RT.</span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 221-231"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liliana L Berube BS , Kwang-ok P Nickel PhD , Mari Iida PhD , Sravani Ramisetty PhD , Prakash Kulkarni PhD , Ravi Salgia MD, PhD , Deric L Wheeler PhD , Randall J Kimple MD, PhD, MBA
{"title":"Radiation Sensitivity: The Rise of Predictive Patient-Derived Cancer Models","authors":"Liliana L Berube BS , Kwang-ok P Nickel PhD , Mari Iida PhD , Sravani Ramisetty PhD , Prakash Kulkarni PhD , Ravi Salgia MD, PhD , Deric L Wheeler PhD , Randall J Kimple MD, PhD, MBA","doi":"10.1016/j.semradonc.2023.03.005","DOIUrl":"10.1016/j.semradonc.2023.03.005","url":null,"abstract":"<div><p><span><span>Patient-derived cancer models have been used for decades to improve our understanding of cancer and test anticancer treatments. Advances in radiation delivery have made these models more attractive for studying </span>radiation sensitizers and understanding an individual patient's </span>radiation sensitivity<span><span>. Advances in the use of patient-derived cancer models lead to a more clinically relevant outcome, although many questions remain regarding the optimal use of patient-derived xenografts and patient-derived </span>spheroid<span> cultures. The use of patient-derived cancer models as personalized predictive avatars through mouse and zebrafish models is discussed, and the advantages and disadvantages of patient-derived spheroids are reviewed. In addition, the use of large repositories of patient-derived models to develop predictive algorithms to guide treatment selection is discussed. Finally, we review methods for establishing patient-derived models and identify key factors that influence their use as both avatars and models of cancer biology.</span></span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 279-286"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9707582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johannes H.A.M. Kaanders PhD , Johan Bussink PhD , Erik H.J.G. Aarntzen PhD , Pètra Braam PhD , Heidi Rütten MD , Richard W.M. van der Maazen PhD , Marcel Verheij PhD , Sven van den Bosch PhD
{"title":"[18F]FDG-PET-Based Personalized Radiotherapy Dose Prescription","authors":"Johannes H.A.M. Kaanders PhD , Johan Bussink PhD , Erik H.J.G. Aarntzen PhD , Pètra Braam PhD , Heidi Rütten MD , Richard W.M. van der Maazen PhD , Marcel Verheij PhD , Sven van den Bosch PhD","doi":"10.1016/j.semradonc.2023.03.006","DOIUrl":"10.1016/j.semradonc.2023.03.006","url":null,"abstract":"<div><p>PET imaging with 2’-deoxy-2’-[18F]fluoro-D-glucose ([18F]FDG) has become one of the pillars in the management of malignant diseases. It has proven value in diagnostic workup, treatment policy, follow-up, and as prognosticator for outcome. [18F]FDG is widely available and standards have been developed for PET acquisition protocols and quantitative analyses. More recently, [18F]FDG-PET is also starting to be appreciated as a decision aid for treatment personalization. This review focuses on the potential of [18F]FDG-PET for individualized radiotherapy dose prescription. This includes dose painting, gradient dose prescription, and [18F]FDG-PET guided response-adapted dose prescription. The current status, progress, and future expectations of these developments for various tumor types are discussed.</p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 287-297"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypoxia-Targeted Dose Painting in Radiotherapy","authors":"Ahmed Salem","doi":"10.1016/j.semradonc.2023.03.009","DOIUrl":"10.1016/j.semradonc.2023.03.009","url":null,"abstract":"<div><p><span><span><span>Hypoxia (oxygen deprivation) occurs in most solid </span>malignancies, albeit with considerable heterogeneity. Hypoxia is associated with an aggressive cancer phenotype by promotion of </span>genomic instability, evasion of anti-cancer therapies including </span>radiotherapy<span><span> and enhancement of metastatic risk. Therefore, hypoxia results in poor cancer outcomes. Targeting hypoxia to improve cancer outcomes is an attractive therapeutic strategy. Hypoxia-targeted dose painting escalates radiotherapy dose to hypoxic sub-volumes, as quantified and spatially mapped using hypoxia imaging. This therapeutic approach could overcome hypoxia-induced radioresistance and improve patient outcomes without the need for hypoxia-targeted </span>drugs. This article will review the premise and underpinning evidence for personalized hypoxia-targeted dose painting. It will present data on relevant hypoxia imaging biomarkers, highlight the challenges and potential benefit of this approach and provide recommendations for future research priorities in this field. Personalized hypoxia-based radiotherapy de-escalation strategies will also be addressed.</span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 298-306"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Theranostics and Patient-Specific Dosimetry","authors":"Bryan Bednarz PhD","doi":"10.1016/j.semradonc.2023.03.011","DOIUrl":"10.1016/j.semradonc.2023.03.011","url":null,"abstract":"<div><p><span><span>Radiopharmaceutical therapy (RPT) is an invigorated form of cancer therapy that systemically delivers targeted radioactive </span>drugs<span><span> to cancer cells<span>. Theranostics is a type of RPT that utilizes imaging, either of the RPT drug directly or a companion diagnostic, to inform whether a patient will benefit from the treatment<span>. Given the ability to image the drug onboard theranostic treatments also lends itself readily to patient-specific dosimetry, which is a physics-based process that determines the overall absorbed dose burden to healthy organs and tissues and tumors </span></span></span>in patients. While companion diagnostics identify who will benefit from RPT treatments, dosimetry determines how much activity these beneficiaries can receive to maximize therapeutic efficacy. Clinical data is starting to accrue suggesting tremendous benefits when dosimetry is performed for RPT patients. RPT dosimetry, which was once performed by </span></span>florid<span> and often inaccurate workflows, can now be performed more efficiently and accurately with FDA-cleared dosimetry software. Therefore, there is no better time for the field of oncology to adopt this form of personalize medicine to improve outcomes for cancer patients.</span></p></div>","PeriodicalId":49542,"journal":{"name":"Seminars in Radiation Oncology","volume":"33 3","pages":"Pages 317-326"},"PeriodicalIF":3.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9968074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}