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Zhang Z, Zhang J, Zheng R, Ye J, Xu B. A Population-Based Tumor-Volume Model for Head and Neck Cancer During Radiation Therapy With a Dynamic Oxygenated Compartment. Int J Radiat Oncol Biol Phys 2024; 120:1159-1171. [PMID: 38871196 DOI: 10.1016/j.ijrobp.2024.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Revised: 04/13/2024] [Accepted: 05/21/2024] [Indexed: 06/15/2024]
Abstract
PURPOSE With the coming era of digital medicine and healthcare technology, mathematical modeling of tumors has become a key step to optimize and realize precision radiation therapy. The purpose of this study was to develop a mathematical model for simulating the change of head and neck (HN) tumor volume during radiation therapy. METHODS AND MATERIALS A formula was developed to describe the dynamic change of oxygenated compartment within a tumor, which was combined with the lethal lesions model to describe various cell processes during radiation therapy, including potentially lethal lesion repair and misrepair, cell proliferation/loss, and tumor reoxygenation. Parameter sensitivity analysis was performed to evaluate the impacts of lesion- and repair-related biological factors on radiation therapy outcomes. RESULTS We tested our model on 14 available patients with HN cancer and compared the performance with 3 other models. The mean error of our model for the 12 good fit cases was 12.2%, which is considerably smaller than that of the linear quadratic model (19.7%), the generalized linear quadratic model (19.1%), and a 4-level cell population model (16.6%). Correlation analysis results revealed that for small tumors, there was a positive correlation (correlation coefficient r=0.9416) between hypoxic fraction (hf) and tumor volume, whereas the correlation became negative and not significant (r=-0.4365) for large tumors. It is demonstrated from sensitivity analysis that the production rate of lethal lesions (ηl) has a far greater impact on tumor volume than other parameters. The hf had an insignificant impact on tumor volume but had a notable influence on the volume of surviving cells. The final volume of surviving cells athf=0.5 was almost 8 ×102 times that of hf=0.01. The potentially lethal lesion-related parameters (the production rate of potentially lethal lessions per unit dose ηpl, the rate of correct repair per unit time εpl, and the rate of binary misrepair per unit time ε2pl) had rather small impacts (<1%) on both tumor volume and the volume of surviving cells, which indicates that the repaired and misrepaired sublethal cells only take up a small portion of the total cancer cell population. CONCLUSIONS A population-based tumor-volume model for HN cancer during radiation therapy with a dynamic oxygenated compartment was developed in this study. Comprehensively considering the damage process of tumor cells caused by radiation therapy, the accurate prediction of the volume change of HN tumors during treatment was revealed. Meanwhile, various cell activities and their principles in the process of antitumor treatment were reflected, which has positive clinical reference significance for radiobiology.
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Affiliation(s)
- Zhengying Zhang
- School of Mathematics and Statistics, Fujian Normal University, Fuzhou, People's Republic of China
| | - Jianping Zhang
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China; Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Fujian Medical University, Fuzhou, People's Republic of China; Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fuzhou, People's Republic of China
| | - Rong Zheng
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China; Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Fujian Medical University, Fuzhou, People's Republic of China; Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fuzhou, People's Republic of China
| | - Jianxiong Ye
- School of Mathematics and Statistics, Fujian Normal University, Fuzhou, People's Republic of China; Key Laboratory of Analytical Mathematics and Applications (Ministry of Education), Fujian Normal University, Fuzhou, People's Republic of China; Fujian Key Laboratory of Analytical Mathematics and Applications, Fujian Normal University, Fuzhou, People's Republic of China; Center for Applied Mathematics of Fujian Province (FJNU), Fuzhou, People's Republic of China.
| | - Benhua Xu
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China; Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Fujian Medical University, Fuzhou, People's Republic of China; Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fuzhou, People's Republic of China.
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Sambasivan K, Barrington SF, Connor SE, Witney TH, Blower PJ, Urbano TG. Is there a role for [ 18F]-FMISO PET to guide dose adaptive radiotherapy in head and neck cancer? A review of the literature. Clin Transl Imaging 2024; 12:137-155. [PMID: 39286295 PMCID: PMC7616449 DOI: 10.1007/s40336-023-00607-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 12/12/2023] [Indexed: 09/19/2024]
Abstract
Purpose Hypoxia is a major cause of radioresistance in head and neck cancer (HNC), resulting in treatment failure and disease recurrence. 18F-fluoromisonidazole [18F]FMISO PET has been proposed as a means of localising intratumoural hypoxia in HNC so that radiotherapy can be specifically escalated in hypoxic regions. This concept may not be deliverable in routine clinical practice, however, given that [18F]FMISO PET is costly, time consuming and difficult to access. The aim of this review was to summarise clinical studies involving [18F]FMISO PET to ascertain whether it can be used to guide radiotherapy treatment in HNC. Methods A comprehensive literature search was conducted on PubMed and Web of Science databases. Studies investigating [18F]FMISO PET in newly diagnosed HNC patients were considered eligible for review. Results We found the following important results from our literature review: 1)Studies have focussed on comparing [18F]FMISO PET to other hypoxia biomarkers, but currently there is no evidence of a strong correlation between [18F]FMISO and these biomarkers.2)The results of [18F]FMISO PET imaging are not necessarily repeatable, and the location of uptake may vary during treatment.3)Tumour recurrences do not always occur within the pretreatment hypoxic volume on [18F]FMISO PET.4)Dose modification studies using [18F]FMISO PET are in a pilot phase and so far, none have demonstrated the efficacy of radiotherapy dose painting according to [18F]FMISO uptake on PET. Conclusions Our results suggest it is unlikely [18F]FMISO PET will be suitable for radiotherapy dose adaptation in HNC in a routine clinical setting. Part of the problem is that hypoxia is a dynamic phenomenon, and thus difficult to delineate on a single scan. Currently, it is anticipated that [18F]FMISO PET will remain useful within the research setting only.
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Affiliation(s)
- Khrishanthne Sambasivan
- Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
| | - Sally F Barrington
- King's College London and Guy's and St Thomas' PET Centre; School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, UK
| | - Steve Ej Connor
- Department of Neuroradiology, King's College Hospital NHS Foundation Trust, London, UK Department of Radiology, Guy's and St Thomas' NHS Foundation Trust, London, UK; School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, King's College London, London, UK
| | - Timothy H Witney
- King's College London, School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, London, United Kingdom
| | - Philip J Blower
- King's College London, School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, London, United Kingdom
| | - Teresa Guerrero Urbano
- Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK; Faculty of Dentistry, Oral & Craniofacial Sciences and School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom
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3
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Abstract
Hypoxia (oxygen deprivation) occurs in most solid malignancies, albeit with considerable heterogeneity. Hypoxia is associated with an aggressive cancer phenotype by promotion of genomic instability, evasion of anti-cancer therapies including radiotherapy 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 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.
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Affiliation(s)
- Ahmed Salem
- Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, Hashemite University, Zarqa, Jordan; Division of Cancer Sciences, University of Manchester, Manchester, UK.
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4
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Hildingsson S, Gebre-Medhin M, Zschaeck S, Adrian G. Hypoxia in relationship to tumor volume using hypoxia PET-imaging in head & neck cancer - A scoping review. Clin Transl Radiat Oncol 2022; 36:40-46. [PMID: 35769424 PMCID: PMC9234341 DOI: 10.1016/j.ctro.2022.06.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 06/08/2022] [Accepted: 06/13/2022] [Indexed: 01/19/2023] Open
Abstract
Background Hypoxia and large tumor volumes are negative prognostic factors for patients with head and neck squamous cell carcinoma (HNSCC) treated with radiation therapy (RT). PET-scanning with specific hypoxia-tracers (hypoxia-PET) can be used to non-invasively assess hypoxic tumor volume. Primary tumor volume is readily available for patients undergoing RT. However, the relationship between hypoxic volume and primary tumor volume is yet an open question. The current study investigates the hypotheses that larger tumors contain both a larger hypoxic volume and a higher hypoxic fraction. Methods PubMed and Embase were systematically searched to identify articles fulfilling the predefined criteria. Individual tumor data (primary tumor volume and hypoxic volume/fraction) was extracted. Relationship between hypoxic volume and primary tumor volume was investigated by linear regression. The correlation between hypoxic fraction and log2(primary tumor volume) was determined for each cohort and in a pooled analysis individual regression slopes and coefficients of determination (R2) were weighted according to cohort size. Results 21 relevant articles were identified and individual data from 367 patients was extracted, out of which 323 patients from 17 studies had quantifiable volumes of interest. A correlation between primary tumor volume and PET-determined hypoxic volume was found (P <.001, R2 = 0.46). Larger tumors had a significantly higher fraction of hypoxia compared with smaller tumors (P<.01). The weighted analysis of all studies revealed that for each doubling of the tumor volume, the hypoxic fraction increased by four percentage points. Conclusion This study shows correlations between primary tumor volume and hypoxic volume as well as primary tumor volume and the hypoxic fraction in patients with HNSCC. The findings suggest that not only do large tumors contain more cancer cells, they also have a higher proportion of potentially radioresistant hypoxic cells. This knowledge can be important when individualizing RT.
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Affiliation(s)
- Sofia Hildingsson
- Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden
| | - Maria Gebre-Medhin
- Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden
| | - Sebastian Zschaeck
- Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Gabriel Adrian
- Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden
- Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden
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Gallez B. The Role of Imaging Biomarkers to Guide Pharmacological Interventions Targeting Tumor Hypoxia. Front Pharmacol 2022; 13:853568. [PMID: 35910347 PMCID: PMC9335493 DOI: 10.3389/fphar.2022.853568] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 06/23/2022] [Indexed: 12/12/2022] Open
Abstract
Hypoxia is a common feature of solid tumors that contributes to angiogenesis, invasiveness, metastasis, altered metabolism and genomic instability. As hypoxia is a major actor in tumor progression and resistance to radiotherapy, chemotherapy and immunotherapy, multiple approaches have emerged to target tumor hypoxia. It includes among others pharmacological interventions designed to alleviate tumor hypoxia at the time of radiation therapy, prodrugs that are selectively activated in hypoxic cells or inhibitors of molecular targets involved in hypoxic cell survival (i.e., hypoxia inducible factors HIFs, PI3K/AKT/mTOR pathway, unfolded protein response). While numerous strategies were successful in pre-clinical models, their translation in the clinical practice has been disappointing so far. This therapeutic failure often results from the absence of appropriate stratification of patients that could benefit from targeted interventions. Companion diagnostics may help at different levels of the research and development, and in matching a patient to a specific intervention targeting hypoxia. In this review, we discuss the relative merits of the existing hypoxia biomarkers, their current status and the challenges for their future validation as companion diagnostics adapted to the nature of the intervention.
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Affiliation(s)
- Bernard Gallez
- Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
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6
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Elamir AM, Stanescu T, Shessel A, Tadic T, Yeung I, Letourneau D, Kim J, Lukovic J, Dawson LA, Wong R, Barry A, Brierley J, Gallinger S, Knox J, O'Kane G, Dhani N, Hosni A, Taylor E. Simulated dose painting of hypoxic sub-volumes in pancreatic cancer stereotactic body radiotherapy. Phys Med Biol 2021; 66. [PMID: 34438383 DOI: 10.1088/1361-6560/ac215c] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 08/26/2021] [Indexed: 12/26/2022]
Abstract
Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour controlin silicoin several sites, predominantly head and neck and lung cancers. Pancreatic cancer presents a more stringent challenge, given its proximity to critical gastro-intestinal organs-at-risk (OARs), anatomic motion, and impediments to reliable PET hypoxia quantification. A radiobiological model was developed to estimate clonogen survival fraction (SF), using18F-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with unresectable pancreatic ductal adenocarcinoma to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: (1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, (2) dose painting plans delivering escalated doses to a maximum of three FAZA-avid hypoxic sub-volumes, (3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and (4), plans with integrated boosts to geometric contractions of the gross tumour volume (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (∼10-5) well above levels required to completely ablate a ∼10 cm3tumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity.
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Affiliation(s)
- Ahmed M Elamir
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Teodor Stanescu
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Andrea Shessel
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada
| | - Tony Tadic
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Ivan Yeung
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada.,Stronach Regional Cancer Centre, Southlake Regional Health Centre, Newmarket, Canada
| | - Daniel Letourneau
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - John Kim
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Jelena Lukovic
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Laura A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Rebecca Wong
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Aisling Barry
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - James Brierley
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Steven Gallinger
- Ontario Institute for Cancer Research, PanCuRx Translational Research Initiative, Toronto, Canada.,Department of Surgery, University of Toronto, Toronto, Canada
| | - Jennifer Knox
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada
| | - Grainne O'Kane
- Ontario Institute for Cancer Research, PanCuRx Translational Research Initiative, Toronto, Canada.,Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada
| | - Neesha Dhani
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada
| | - Ali Hosni
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Edward Taylor
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Canada
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Marcus C, Sheikhbahaei S, Shivamurthy VKN, Avey G, Subramaniam RM. PET Imaging for Head and Neck Cancers. Radiol Clin North Am 2021; 59:773-788. [PMID: 34392918 DOI: 10.1016/j.rcl.2021.05.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Head and neck cancers are commonly encountered cancers in clinical practice in the United States. Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT has been clinically applied in staging, occult primary tumor detection, treatment planning, response assessment, follow-up, recurrent disease detection, and prognosis prediction in these patients. Alternative PET tracers remain investigational and can provide additional valuable information such as radioresistant tumor hypoxia. The recent introduction of 18F-FDG PET/MR imaging has provided the advantage of combining the superior soft tissue resolution of MR imaging with the functional information provided by 18F-FDG PET. This article is a concise review of recent advances in PET imaging in head and neck cancer.
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Affiliation(s)
- Charles Marcus
- Department of Nuclear Medicine and Molecular Imaging, Emory University Hospital, Atlanta, GA, USA.
| | - Sara Sheikhbahaei
- Department of Radiology, Johns Hopkins Medical Institutions, 601 N. Caroline Street, JHOC 3235, Baltimore, MD 21287, USA
| | - Veeresh Kumar N Shivamurthy
- Epilepsy Center, St. Francis Hospital and Medical Center, Trinity Health of New England, 114 Woodland Street, Hartford, CT 06105, USA
| | - Greg Avey
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave #3284, Madison, WI 53792, USA
| | - Rathan M Subramaniam
- Dean's Office, Otago Medical School, University of Otago, 201 Great King Street, Dunedin 9016, New Zealand
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Carles M, Fechter T, Grosu AL, Sörensen A, Thomann B, Stoian RG, Wiedenmann N, Rühle A, Zamboglou C, Ruf J, Martí-Bonmatí L, Baltas D, Mix M, Nicolay NH. 18F-FMISO-PET Hypoxia Monitoring for Head-and-Neck Cancer Patients: Radiomics Analyses Predict the Outcome of Chemo-Radiotherapy. Cancers (Basel) 2021; 13:3449. [PMID: 34298663 PMCID: PMC8303992 DOI: 10.3390/cancers13143449] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/06/2021] [Accepted: 07/06/2021] [Indexed: 12/24/2022] Open
Abstract
Tumor hypoxia is associated with radiation resistance and can be longitudinally monitored by 18F-fluoromisonidazole (18F-FMISO)-PET/CT. Our study aimed at evaluating radiomics dynamics of 18F-FMISO-hypoxia imaging during chemo-radiotherapy (CRT) as predictors for treatment outcome in head-and-neck squamous cell carcinoma (HNSCC) patients. We prospectively recruited 35 HNSCC patients undergoing definitive CRT and longitudinal 18F-FMISO-PET/CT scans at weeks 0, 2 and 5 (W0/W2/W5). Patients were classified based on peritherapeutic variations of the hypoxic sub-volume (HSV) size (increasing/stable/decreasing) and location (geographically-static/geographically-dynamic) by a new objective classification parameter (CP) accounting for spatial overlap. Additionally, 130 radiomic features (RF) were extracted from HSV at W0, and their variations during CRT were quantified by relative deviations (∆RF). Prediction of treatment outcome was considered statistically relevant after being corrected for multiple testing and confirmed for the two 18F-FMISO-PET/CT time-points and for a validation cohort. HSV decreased in 64% of patients at W2 and in 80% at W5. CP distinguished earlier disease progression (geographically-dynamic) from later disease progression (geographically-static) in both time-points and cohorts. The texture feature low grey-level zone emphasis predicted local recurrence with AUCW2 = 0.82 and AUCW5 = 0.81 in initial cohort (N = 25) and AUCW2 = 0.79 and AUCW5 = 0.80 in validation cohort. Radiomics analysis of 18F-FMISO-derived hypoxia dynamics was able to predict outcome of HNSCC patients after CRT.
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Affiliation(s)
- Montserrat Carles
- Department of Radiation Oncology, Division of Medical Physics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (T.F.); (B.T.); (D.B.)
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- La Fe Health Research Institute, Biomedical Imaging Research Group (GIBI230-PREBI) and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), 46026 Valencia, Spain;
| | - Tobias Fechter
- Department of Radiation Oncology, Division of Medical Physics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (T.F.); (B.T.); (D.B.)
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
| | - Anca L. Grosu
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Arnd Sörensen
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Benedikt Thomann
- Department of Radiation Oncology, Division of Medical Physics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (T.F.); (B.T.); (D.B.)
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
| | - Raluca G. Stoian
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Nicole Wiedenmann
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Alexander Rühle
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Constantinos Zamboglou
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Juri Ruf
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Luis Martí-Bonmatí
- La Fe Health Research Institute, Biomedical Imaging Research Group (GIBI230-PREBI) and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), 46026 Valencia, Spain;
| | - Dimos Baltas
- Department of Radiation Oncology, Division of Medical Physics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (T.F.); (B.T.); (D.B.)
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
| | - Michael Mix
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Nuclear Medicine, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Nils H. Nicolay
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (A.L.G.); (A.S.); (R.G.S.); (N.W.); (A.R.); (C.Z.); (J.R.); (M.M.); (N.H.N.)
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
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9
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Ventura M, Bernards N, De Souza R, Fricke IB, Hendriks BS, Fitzgerald JB, Lee H, Klinz SG, Zheng J. Longitudinal PET Imaging to Monitor Treatment Efficacy by Liposomal Irinotecan in Orthotopic Patient-Derived Pancreatic Tumor Models of High and Low Hypoxia. Mol Imaging Biol 2021; 22:653-664. [PMID: 31482415 PMCID: PMC7782415 DOI: 10.1007/s11307-019-01374-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Purpose Hypoxia is linked to aggressiveness, resistance to therapy, and poor prognosis of pancreatic tumors. Liposomal irinotecan (nal-IRI, ONIVYDE®) has shown potential in reducing hypoxia in the HT29 colorectal cancer model, and here, we investigate its therapeutic activity and ability to modulate hypoxia in patient-derived orthotopic tumor models of pancreatic cancer. Procedures Mice were randomized into nal-IRI treated and untreated controls. Magnetic resonance imaging was used for monitoring treatment efficacy, positron emission tomography (PET) imaging with F-18-labelled fluoroazomycinarabinoside ([18F]FAZA) for tumor hypoxia quantification, and F-18-labelled fluorothymidine ([18F]FLT) for tumor cell proliferation. Results The highly hypoxic OCIP51 tumors showed significant response following nal-IRI treatment compared with the less hypoxic OCIP19 tumors. [18F]FAZA-PET detected significant hypoxia reduction in treated OCIP51 tumors, 8 days before significant changes in tumor volume. OCIP19 tumors also responded to therapy, although tumor volume control was not accompanied by any reduction in [18F]FAZA uptake. In both models, no differences were observable in [18F]FLT uptake in treated tumors compared with control mice. Conclusions Hypoxia modulation may play a role in nal-IRI’s mechanism of action. Nal-IRI demonstrated greater anti-tumor activity in the more aggressive and hypoxic tumor model. Furthermore, hypoxia imaging provided early prediction of treatment response. Electronic supplementary material The online version of this article (10.1007/s11307-019-01374-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Manuela Ventura
- TECHNA Institute for the Advancement of Technology for Health, University Health Network, Toronto, Ontario, Canada
| | - Nicholas Bernards
- TECHNA Institute for the Advancement of Technology for Health, University Health Network, Toronto, Ontario, Canada
| | - Raquel De Souza
- TECHNA Institute for the Advancement of Technology for Health, University Health Network, Toronto, Ontario, Canada
| | - Inga B Fricke
- TECHNA Institute for the Advancement of Technology for Health, University Health Network, Toronto, Ontario, Canada
| | | | | | - Helen Lee
- Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA
| | - Stephan G Klinz
- Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA
- Ipsen Bioscience, Cambridge, MA, USA
| | - Jinzi Zheng
- TECHNA Institute for the Advancement of Technology for Health, University Health Network, Toronto, Ontario, Canada.
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
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10
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Lopes S, Ferreira S, Caetano M. PET/CT in the Evaluation of Hypoxia for Radiotherapy Planning in Head and Neck Tumors: Systematic Literature Review. J Nucl Med Technol 2021; 49:107-113. [PMID: 33361182 DOI: 10.2967/jnmt.120.249540] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 11/09/2020] [Indexed: 11/16/2022] Open
Abstract
PET/CT combines imaging at the molecular level along with imaging at the anatomic level, which, with the administration of a hypoxia-sensitive radiopharmaceutical, allows evaluation of tissue oxygenation. Methods: This work consisted of a systematic literature review that included websites, books, and articles dated from July 1997 to December 2019. The aim was to identify the PET radiopharmaceuticals best suited to the detection of cell hypoxia and to recognize the benefits for planning intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT). Results: Hypoxia affects the likelihood of cure for head and neck tumors, reducing the success rate. Radiopharmaceuticals such as 18F-fluoromisonidazole, 18F-fluoroerythronitromidazole, and 18F-HX4 (18F-3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol) allow the delineation of hypoxic subvolumes within the target volume to optimize IMRT/VMAT. Conclusion: Identification of hypoxic areas with PET/CT imaging and use of subsequent IMRT/VMAT allows for possible escalation of radiation dose in radioresistant subvolumes, with a consequent decrease in relapses and an increased likelihood of disease-free survival.
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Affiliation(s)
- Susana Lopes
- Nottingham University Hospitals, Nottingham, United Kingdom
| | - Sara Ferreira
- Dr. Lopes Dias School of Health-Polytechnic Institute of Castelo Branco, Castelo Branco, Portugal; and
| | - Marco Caetano
- Lisbon School of Health Technology-Polytechnic Institute of Lisbon, Lisbon, Portugal
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11
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Zeng J, Bowen SR. Treatment Intensification in Locally Advanced/Unresectable NSCLC Through Combined Modality Treatment and Precision Dose Escalation. Semin Radiat Oncol 2021; 31:105-111. [PMID: 33610266 DOI: 10.1016/j.semradonc.2020.11.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The best survival for patients with unresectable, locally advanced NSCLC is currently achieved through concurrent chemoradiation followed by durvalumab for a year. Despite the best standard of care treatment, the majority of patients still develop disease recurrence, which could be distant and/or local. Trials continue to try and improve outcomes for patients with unresectable NSCLC, typically through treatment intensification, with the addition of more systemic agents, or more radiation dose to the tumor. Although RTOG 0617 showed that uniform dose escalation across an unselected population of patients undergoing chemoradiation is not beneficial, efforts continue to select patients and tumor subsets that are likely to benefit from dose escalation. This review describes some of the ongoing therapeutic trials in unresectable NSCLC, with an emphasis on quantitative imaging and precision radiation dose escalation.
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Affiliation(s)
- Jing Zeng
- Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA.
| | - Stephen R Bowen
- Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA; Department of Radiology, University of Washington School of Medicine, Seattle, WA
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12
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Kawamura M, Yoshimura M, Shimizu Y, Sano K, Ishimori T, Nakamoto Y, Mizowaki T, Hiraoka M. Evaluation of Optimal Post-Injection Timing of Hypoxic Imaging with 18F-Fluoromisonidazole-PET/CT. Mol Imaging Biol 2021; 23:597-603. [PMID: 33475945 DOI: 10.1007/s11307-021-01580-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 12/26/2020] [Accepted: 01/06/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE Positron emission tomography (PET)/computed tomography (CT) using 18F-fluoromisonidazole (FMISO) has been used as an imaging tool for tumour hypoxia. However, it remains unclear whether they are useful when scanning is performed earlier, e.g. at 2-h post-injection with a high sensitivity PET scanner. This study aimed to investigate the relationship between quantitative values in 18F-fluoromisonidazole (18F-FMISO)-PET obtained at 2- and 4-h post-injection in patients with head and neck cancer. PROCEDURES We enrolled 20 patients with untreated locally advanced head and neck cancer who underwent 18F-FMISO-PET/CT scan between August 2015 and March 2018 at our institute. Image acquisition was performed 2 h and 4 h after 18F-FMISO administration using a combined PET/CT scanner. The SUVmax, SUVmean, SUVpeak, tumour-to-blood ratio (TBR), tumour-to-muscle ratio (TMR), metabolic tumour volume (MTV), and total lesion hypoxia (TLH) were measured in the region of interest of the primary tumour. We evaluated the between-image Spearman's rank correlation coefficients and percentage differences in the quantitative values. The locations of the maximum uptake pixel were identified in both scans, and the distance between them was measured. RESULTS The mean (SD) SUVmax at 2 h and 4 h was 2.2(0.7) and 2.4(0.8), respectively. The Spearman's rank correlation coefficients (ρ) and mean (SD) of the percentage differences of the measures were as follows: SUVmax (0.97; 7.0 [5.1]%), SUVmean (0.97; 5.2 [5.8]%), SUVpeak (0.94; 5.3 [4.7]%), TBR (0.96; 14.2 [9.8]%), TMR (0.96; 14.7 [8.4]%), MTV (0.98; 39.9 [41.3]%), and TLH (0.98; 40.1 [43.4]%). There were significant between-scan correlations in all quantitative values. The mean (SD) distance between the two maximum uptake pixels was 7.3 (5.3) mm. CONCLUSIONS We observed a high correlation between the quantitative values at 2 h and 4 h. When using a combined high-quality PET/CT, the total examination time for FMISO-PET can be shortened by skipping the 4-h scan.
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Affiliation(s)
- Mitsue Kawamura
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Michio Yoshimura
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Yoichi Shimizu
- Division of Clinical Radiology Service, Kyoto University Hospital, Kyoto, Japan
| | - Kohei Sano
- Division of Clinical Radiology Service, Kyoto University Hospital, Kyoto, Japan
| | - Takayoshi Ishimori
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takashi Mizowaki
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Masahiro Hiraoka
- Department of Radiation Oncology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
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13
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Chen S, Yan D, Qin A, Maniawski P, Krauss DJ, Wilson GD. Effect of uncertainties in quantitative 18 F-FDG PET/CT imaging feedback for intratumoral dose-response assessment and dose painting by number. Med Phys 2020; 47:5681-5692. [PMID: 32966627 DOI: 10.1002/mp.14482] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 08/09/2020] [Accepted: 08/18/2020] [Indexed: 01/14/2023] Open
Abstract
PURPOSE Intratumoral dose response can be detected using serial fluoro-2-deoxyglucose-(FDG) positron emission tomography (PET)/computed tomography (CT) imaging feedback during treatment and used to guide adaptive dose painting by number (DPbN). However, to reliably implement this technique, the effect of uncertainties in quantitative PET/CT imaging feedback on tumor voxel dose-response assessment and DPbN needs to be determined and reduced. METHODS Three major uncertainties, induced by (a) PET imaging partial volume effect (PVE) and (b) tumor deformable image registration (DIR), and (c) variation of the time interval between FDG injection and PET image acquisition (TI), were determined using serial FDG-PET/CT images acquired during chemoradiotherapy of 18 head and neck cancer patients. PET imaging PVE was simulated using the discrepancy between with and without iterative deconvolution-based PVE corrections. Effect of tumor DIR uncertainty was simulated using the discrepancy between two DIR algorithms, including one with and one without soft-tissue mechanical correction for the voxel displacement. The effect of TI variation was simulated using linear interpolation on the dual-point PET/CT images. Tumor voxel pretreatment metabolic activity (SUV0 ) and dose-response matrix (DRM) discrepancies induced by each of the three uncertainties were quantified, respectively. Adverse effects of tumor voxel SUV0 and DRM discrepancies on tumor control probability (TCP) in DPbN were assessed. RESULTS Partial volume effect and TI variations of 10 mins induced a mean ± standard deviation (SD) of tumor voxel SUV0 discrepancies to be -0.7% ± 9.2% and 0% ± 4.8%, respectively. Tumor voxel DRM discrepancies induced by PVE, tumor DIR discrepancy, and TI variations were 0.6% ± 8.9%, 1.7% ± 9.1%, and 0% ± 7%, respectively. Partial volume effect induced SUV0 and DRM discrepancies correlated significantly with the tumor shape and FDG uptake heterogeneity. Tumor DIR uncertainty-induced DRM discrepancy correlated significantly with the tumor volume and shrinkage during treatment. Among the three uncertainties, PVE dominated the adverse effects on the TCP, with a mean ± SD of TCP reduction to be 12.7% ± 9.8% for all tumors if no compensation was applied for. CONCLUSIONS Effect of uncertainties in quantitative FDG-PET/CT imaging feedback on intratumoral dose-response quantification was not negligible. These uncertainties primarily caused by PVE and tumor DIR were highly dependent on individual tumor shape, volume, shrinkage during treatment, and pretreatment SUV heterogeneity, which can be managed individually. The adverse effects of these uncertainties could be minimized by using proper PVE corrections and DIR methods and compensated for in the clinical implementation of DPbN.
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Affiliation(s)
- Shupeng Chen
- Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 48073, USA.,Medical Physics, School of Medicine, Wayne State University, Detroit, MI, 48201, USA
| | - Di Yan
- Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 48073, USA
| | - An Qin
- Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 48073, USA
| | - Piotr Maniawski
- Advanced Molecular Imaging, Philips, Cleveland, OH, 44143, USA
| | - Daniel J Krauss
- Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 48073, USA
| | - George D Wilson
- Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 48073, USA
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14
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Abstract
Head and neck cancers are commonly encountered malignancies in the United States, of which the majority are attributed to squamous cell carcinoma. 18F-FDG-PET/CT has been well established in the evaluation, treatment planning, prognostic implications of these tumors and is routinely applied for the management of patients with these cancers. Many alternative investigational PET radiotracers have been extensively studied in the evaluation of these tumors. Although these radiotracers have not been able to replace 18F-FDG-PET/CT in routine clinical practice currently, they may provide important additional information about the biological mechanisms of these tumors, such as foci of tumor hypoxia as seen on hypoxia specific PET radiotracers such as 18F-Fluoromisonidazole (18F-FMISO), which could be useful in targeting radioresistant hypoxic tumor foci when treatment planning. There are multiple other hypoxia-specific PET radiotracers such as 18F-Fluoroazomycinarabinoside (FAZA), 18F-Flortanidazole (HX4), which have been evaluated similarly, of which 18F-Fluoromisonidazole (18F-FMISO) has been the most investigated. Other radiotracers frequently studied in the evaluation of these tumors include radiolabeled amino acid PET radiotracers, which show increased uptake in tumor cells with limited uptake in inflammatory tissue, which can be useful especially in differentiating postradiation inflammation from residual and/or recurrent disease. 18F-Fluorothymidine (FLT) is localized intracellularly by nucleoside transport and undergoes phosphorylation thereby being retained within tumor cells and can serve as an indicator of tumor proliferation. Decrease in radiotracer activity following treatment can be an early indicator of treatment response. This review aims at synthesizing the available literature on the most studied non-FDG-PET/CT in head and neck cancer.
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Affiliation(s)
- Charles Marcus
- Department of Radiology, West Virginia University, Morgantown, WV.
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15
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Wiedenmann N, Grosu AL, Büchert M, Rischke HC, Ruf J, Bielak L, Majerus L, Rühle A, Bamberg F, Baltas D, Hennig J, Mix M, Bock M, Nicolay NH. The utility of multiparametric MRI to characterize hypoxic tumor subvolumes in comparison to FMISO PET/CT. Consequences for diagnosis and chemoradiation treatment planning in head and neck cancer. Radiother Oncol 2020; 150:128-135. [PMID: 32544609 DOI: 10.1016/j.radonc.2020.06.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/02/2020] [Accepted: 06/10/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND PURPOSE Hypoxia is an essential metabolic marker that determines chemo- and radiation resistance in head-and-neck squamous cell carcinoma (HNSCC) patients. Our exploratory analysis aimed to identify multiparametric MRI (mpMRI) parameters linked to hypoxia that might be used as surrogate for [18F]FMISO-PET in diagnosis and chemoradiation treatment (CRT) of HNSCC. MATERIALS AND METHODS 21 patients undergoing definitive CRT for HNSCC were prospectively imaged with serial [18F]FMISO-PET and 3 Tesla mpMRI for T1- and T2-weighted and dynamic contrast-enhanced perfusion and diffusion-weighted measurements (ktrans, ve, kep, ADC) in weeks 0, 2 and 5 and FDG-PET in week 0. [18F]FMISO-PET-derived hypoxic subvolumes (HSV) and complementary non-hypoxic subvolumes (nonHSV) were created for tumor and lymph nodes and projected on the mpMRI scans after PET/MRI co-registration. MpMRI and [18F]FMISO-PET parameters within HSVs and nonHSVs were statistically compared. RESULTS FMISO-PET-based HSVs of the primary tumors on MRI were characterized by lower ADC at all time points (p = 0.012 at baseline; p = 0.015 in week 2) and reduced interstitial space volume fraction ve and perfusion ktrans at baseline (p = 0.006, p = 0.047) compared to nonHSVs. Hypoxic lymph nodes were characterized by significantly lower ADC values at baseline (p = 0.039), but not at later time points and a reduction in ktrans-based perfusion at week 2 (p = 0.018). CONCLUSION MpMRI parameters differ significantly between hypoxic and non-hypoxic tumor regions, defined on FMISO-PET/CT as gold standard and might represent surrogate markers for tumor hypoxia. These findings suggest that mpMRI may be useful in the future as a surrogate modality for hypoxia imaging in order to personalize CRT.
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Affiliation(s)
- Nicole Wiedenmann
- Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Martin Büchert
- Department of Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Hans C Rischke
- Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Nuclear Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Juri Ruf
- Department of Nuclear Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Lars Bielak
- Department of Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Liette Majerus
- Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Alexander Rühle
- Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Fabian Bamberg
- Department of Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Dimos Baltas
- Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jürgen Hennig
- Department of Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Mix
- Department of Nuclear Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Bock
- Department of Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nils H Nicolay
- Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
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[ 18F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials. Clin Transl Radiat Oncol 2020; 23:9-15. [PMID: 32368624 PMCID: PMC7184102 DOI: 10.1016/j.ctro.2020.04.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 04/06/2020] [Indexed: 11/20/2022] Open
Abstract
Introduction The presence of hypoxia in head-and-neck squamous cell carcinoma is a negative prognostic factor. PET imaging with [18F] HX4 can be used to visualize hypoxia, but it is currently unknown how this correlates with prognosis. We investigated the prognostic value of [18F] HX4 PET imaging in patients treated with definitive radio(chemo)therapy (RTx). Materials and methods We analyzed 34 patients included in two prospective clinical trials (NCT01347281, NCT01504815). Static [18F] HX4 PET-CT images were collected, both pre-treatment (median 4 days before start RTx, range 1-16), as well as during RTx (median 13 days after start RTx, range 3-17 days). Static uptake at both time points (n = 33 pretreatment, n = 28 during RTx) and measured changes in hypoxic fraction (HF) and hypoxic volume (HV) (n = 27 with 2 time points) were analyzed. Univariate cox analyses were done for local progression free survival (PFS) and overall survival (OS) at both timepoints. Change in uptake was analyzed by comparing outcome with Kaplan-Meier curves and log-rank test between patients with increased and decreased/stable hypoxia, similarly between patients with and without residual hypoxia (rHV = ratio week 2/baseline HV with cutoff 0.2). Voxelwise Spearman correlation coefficients were calculated between normalized [18F] HX4 PET uptake at baseline and week 2. Results Analyses of static images showed no prognostic value for [18F] HX4 uptake. Analysis of dynamic changes showed that both OS and local PFS were significantly shorter (log-rank P < 0.05) in patients with an increase in HV during RTx and OS was significantly shorter in patients with rHV, with no correlation to HPV-status. The voxel-based correlation to evaluate spatial distribution yielded a median Spearman correlation coefficient of 0.45 (range 0.11-0.65). Conclusion The change of [18F] HX4 uptake measured on [18F] HX4 PET early during treatment can be considered for implementation in predictive models. With these models patients with a worse prognosis can be selected for treatment intensification.
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17
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Rezaee L. Optimization of treatment planning for hypoxic tumours and re-modulation of radiation intensity in heavy-ion radiotherapy. Rep Pract Oncol Radiother 2020; 25:68-78. [PMID: 31889925 DOI: 10.1016/j.rpor.2019.12.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 09/30/2019] [Accepted: 12/13/2019] [Indexed: 12/26/2022] Open
Abstract
Aim The purpose of this study is to optimize treatment planning in carbon ion radiotherapy, taking into account the effect of tumour hypoxia. Background In conventional hadron therapy, the goal is to create a homogenous dose in the tumour area and, thus, achieve a uniform cell survival level. Since the induction of a specific damage to cells is directly influenced by the level of hypoxia in the tissue, the varying oxygen pressure in the different regions of hypoxic tumours would disrupt the uniformity of the cell survival level. Materials and methods Using the Geant4 Monte Carlo Code, the physical dose profile and dose-averaged linear energy transfer were calculated in the tumour. Then, the oxygen enhancement ratio in different areas of the tumour were compared with different pressures. Results Modulations of radiation intensities as well as energies of ion beams were calculated, both considering and disregarding the effect of hypoxia, and the required dose profiles were compared with each other. Cell survival levels were also compared between the two methods. An equation was obtained for re-modulating the beams in the presence of hypoxia, and radiation weighting factors were extracted for the beam intensities. Conclusion The results show that taking the effect of hypoxia into account would cause the reduction of average doses delivered to the tumour tissues up to 1.54 times. In this regard, the required dose is reduced by 1.63 times in the healthy tissues before the tumour. This will result in an effective protection of healthy tissues around the tumour.
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Affiliation(s)
- Ladan Rezaee
- Department of Physics, Shiraz Branch, Islamic Azad University, Shiraz, Iran
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Giammarile F, Castellucci P, Dierckx R, Estrada Lobato E, Farsad M, Hustinx R, Jalilian A, Pellet O, Rossi S, Paez D. Non-FDG PET/CT in Diagnostic Oncology: a pictorial review. Eur J Hybrid Imaging 2019; 3:20. [PMID: 34191163 PMCID: PMC8218094 DOI: 10.1186/s41824-019-0066-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 10/22/2019] [Indexed: 11/25/2022] Open
Abstract
Positron emission tomography/computed tomography (PET/CT) is currently one of the main imaging modalities for cancer patients worldwide. Fluorodeoxyglucose (FDG) PET/CT has earned its global recognition in the modern management of cancer patients and is rapidly becoming an important imaging modality for patients with cardiac, neurological, and infectious/inflammatory conditions. Despite its proven benefits, FDG has limitations in the assessment of several relevant tumours such as prostate cancer. Therefore, there has been a pressing need for the development and clinical application of different PET radiopharmaceuticals that could image these tumours more precisely. Accordingly, several non-FDG PET radiopharmaceuticals have been introduced into the clinical arena for management of cancer. This trend will undoubtedly continue to spread internationally. The use of PET/CT with different PET radiopharmaceuticals specific to tumour type and biological process being assessed is part of the personalised precision medicine approach. The objective of this publication is to provide a case-based method of understanding normal biodistribution, variants, and pitfalls, including several examples of different imaging appearances for the main oncological indications for each of the new non-FDG PET radiopharmaceuticals. This should facilitate the interpretation and recognition of common variants and pitfalls to ensure that, in clinical practice, the official report is accurate and helpful. Some of these radiopharmaceuticals are already commercially available in many countries (e.g. 68Ga-DOTATATE and DOTATOC), others are in the process of becoming available (e.g. 68Ga-PSMA), and some are still being researched. However, this list is subject to change as some radiopharmaceuticals are increasingly utilised, while others gradually decrease in use.
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Affiliation(s)
- Francesco Giammarile
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
| | - Paolo Castellucci
- Department of Nuclear Medicine, Sant'Orsola-Malpighi Hospital, 40138, Bologna, Italy
| | - Rudi Dierckx
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands
| | - Enrique Estrada Lobato
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| | - Mohsen Farsad
- Department of Nuclear Medicine, Bolzano Hospital, Bolzano, Italy
| | - Roland Hustinx
- Department of Nuclear Medicine, CHU Liège, University of Liège, Liège, Belgium
| | - Amirreza Jalilian
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| | - Olivier Pellet
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| | - Susana Rossi
- Centro Uruguayo de Imagenología Molecular (CUDIM), Montevideo, Uruguay
| | - Diana Paez
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
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19
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Hrinivich WT, McNutt TR, Meyer JJ. Radiation treatment planning with embedded dose escalation. Radiat Oncol 2019; 14:145. [PMID: 31412952 PMCID: PMC6693221 DOI: 10.1186/s13014-019-1348-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 07/26/2019] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Heterogeneous target doses are a common by-product from attempts to improve normal tissue sparing in radiosurgery treatment planning. These regions of escalated dose within the target may increase tumor control probability (TCP). Purposely embedding hot spots within tumors during optimization may also increase the TCP. This study discusses and compares five optimization approaches that not only eliminate homogeneity constraints, but also maximize heterogeneity and internal dose escalation. METHODS Co-planar volumetric modulated arc therapy (VMAT) plans were produced for virtual spherical targets with 2-8 cm diameters, minimum target dose objectives of 25 Gy, and objectives to minimize normal tissue dose. Five other sets of plans were produced with additional target dose objectives: 1) minimum dose-volume histogram (DVH) objective on 10% of the target 2) minimum dose objective on a sub-structure within the target, and 3-5) minimum generalized equivalent uniform dose (gEUD) objectives assuming three different volume-effect parameters. Plans were normalized to provide equivalent maximum OAR dose and were compared in terms of target D0.1 cc, ratio of V12.5 Gy to PTV volume (R50%), monitor units per 5 Gy fraction (MU), and mean multi-leaf collimator (MLC) segment size. All planning approaches were also applied to a clinical patient dataset and compared. RESULTS Mean ± standard deviation metrics achievable using the baseline and experimental approaches 1-5) included D0.1 cc: 27.7 ± 0.8, 64.6 ± 10.5, 56.5 ± 10.3, 48.9 ± 5.7, 44.8 ± 5.0, and 37.4 ± 4.5 Gy. R50%: 4.64 ± 3.27, 5.15 ± 2.32, 4.83 ± 2.64, 4.42 ± 1.83, 4.45 ± 1.88, and 4.21 ± 1.75. MU: 795 ± 27, 1988 ± 222, 1766 ± 259, 1612 ± 112, 1524 ± 90, and 1362 ± 146. MLC segment size: 4.7 ± 1.6, 2.3 ± 0.7, 2.6 ± 0.8, 2.7 ± 0.7, 2.7 ± 0.8, and 2.8 ± 0.8 cm. CONCLUSIONS The DVH-based approach provided the highest embedded doses for all target diameters and patient example with modest increases in R50%, achieved by decreasing MLC segment size while increasing MU. These results suggest that embedding doses > 220% of tumor margin dose is feasible, potentially improving TCP for solid tumors.
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Affiliation(s)
- William T Hrinivich
- Dept. of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 N Broadway St. Weinberg Suite 1440, Baltimore, MD, 21231, USA.
| | - Todd R McNutt
- Dept. of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 N Broadway St. Weinberg Suite 1440, Baltimore, MD, 21231, USA
| | - Jeffrey J Meyer
- Dept. of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 N Broadway St. Weinberg Suite 1440, Baltimore, MD, 21231, USA
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20
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Zou W, Dong L, Kevin Teo BK. Current State of Image Guidance in Radiation Oncology: Implications for PTV Margin Expansion and Adaptive Therapy. Semin Radiat Oncol 2018; 28:238-247. [PMID: 29933883 DOI: 10.1016/j.semradonc.2018.02.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Image guidance technology has evolved and seen widespread application in the past several decades. Advancements in the diagnostic imaging field have found new applications in radiation oncology and promoted the development of therapeutic devices with advanced imaging capabilities. A recent example is the development of linear accelerators that offer magnetic resonance imaging for real-time imaging and online adaptive planning. Volumetric imaging, in particular, offers more precise localization of soft tissue targets and critical organs which reduces setup uncertainty and permit the use of smaller setup margins. We present a review of the status of current imaging modalities available for radiation oncology and its impact on target margins and use for adaptive therapy.
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Affiliation(s)
- Wei Zou
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
| | - Lei Dong
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA
| | - Boon-Keng Kevin Teo
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA
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21
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Han K, Shek T, Vines D, Driscoll B, Fyles A, Jaffray D, Keller H, Metser U, Pintilie M, Xie J, Yeung I, Milosevic M. Measurement of Tumor Hypoxia in Patients With Locally Advanced Cervical Cancer Using Positron Emission Tomography with 18F-Fluoroazomyin Arabinoside. Int J Radiat Oncol Biol Phys 2018; 102:1202-1209. [PMID: 29680257 DOI: 10.1016/j.ijrobp.2018.02.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 02/11/2018] [Accepted: 02/20/2018] [Indexed: 01/25/2023]
Abstract
PURPOSE To assess cervical tumor hypoxia using the hypoxia tracer 18F-fluoroazomycin arabinoside (18F-FAZA) and compare different reference tissues and thresholds for quantifying tumor hypoxia. METHODS AND MATERIALS Twenty-seven patients with cervical cancer were studied prospectively by positron emission tomography (PET) imaging with 18F-FAZA before starting standard chemoradiation. The hypoxic volume was defined as all voxels within a tumor (T) with standardized uptake values (SUVs) greater than 3 standard deviations from the mean gluteus maximus muscle SUV value (M) or SUVs greater than 1 to 1.4 times the mean SUV value of the left ventricle, a blood (B) surrogate. The hypoxic fraction was defined as the ratio of the number of hypoxic voxels to the total number of tumor voxels. RESULTS A 18F-FAZA-PET hypoxic volume could be identified in the majority of cervical tumors (89% when using T/M or T/B > 1.2 as threshold) on the 2-hour static scan. The hypoxic fraction ranged from 0% to 99% (median 31%) when defined using the T/M threshold and from 0% to 78% (median 32%) with the T/B > 1.2 threshold. Hypoxic volumes derived from the different thresholds were highly correlated (Spearman's correlation coefficient ρ between T/M and T/B > 1-1.4 were 0.82-0.91), as were hypoxic fractions (0.75-0.85). Compartmental analysis of the dynamic scans showed k3, the FAZA accumulation constant, to be strongly correlated with hypoxic fraction defined using the T/M (Spearman's ρ=0.72) and T/B > 1.2 thresholds (0.76). CONCLUSIONS Hypoxia was detected in the majority of cervical tumors on 18F-FAZA-PET imaging. The extent of hypoxia varied markedly between tumors but not significantly with different reference tissues/thresholds.
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Affiliation(s)
- Kathy Han
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
| | - Tina Shek
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Quantitative Imaging for Personalized Cancer Medicine, Techna Institute, University Health Network, Toronto, Ontario, Canada
| | - Douglass Vines
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Quantitative Imaging for Personalized Cancer Medicine, Techna Institute, University Health Network, Toronto, Ontario, Canada
| | - Brandon Driscoll
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Quantitative Imaging for Personalized Cancer Medicine, Techna Institute, University Health Network, Toronto, Ontario, Canada
| | - Anthony Fyles
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - David Jaffray
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Quantitative Imaging for Personalized Cancer Medicine, Techna Institute, University Health Network, Toronto, Ontario, Canada
| | - Harald Keller
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Quantitative Imaging for Personalized Cancer Medicine, Techna Institute, University Health Network, Toronto, Ontario, Canada
| | - Ur Metser
- Joint Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada; Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
| | - Melania Pintilie
- Department of Biostatistics, University Health Network, Toronto, Ontario, Canada
| | - Jason Xie
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Ivan Yeung
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Quantitative Imaging for Personalized Cancer Medicine, Techna Institute, University Health Network, Toronto, Ontario, Canada
| | - Michael Milosevic
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
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22
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Epel B, Maggio MC, Barth ED, Miller RC, Pelizzari CA, Krzykawska-Serda M, Sundramoorthy SV, Aydogan B, Weichselbaum RR, Tormyshev VM, Halpern HJ. Oxygen-Guided Radiation Therapy. Int J Radiat Oncol Biol Phys 2018; 103:977-984. [PMID: 30414912 DOI: 10.1016/j.ijrobp.2018.10.041] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 10/15/2018] [Accepted: 10/29/2018] [Indexed: 12/18/2022]
Abstract
PURPOSE It has been known for over 100 years that tumor hypoxia, a near-universal characteristic of solid tumors, decreases the curative effectiveness of radiation therapy. However, to date, there are no reports that demonstrate an improvement in radiation effectiveness in a mammalian tumor on the basis of tumor hypoxia localization and local hypoxia treatment. METHODS AND MATERIALS For radiation targeting of hypoxic subregions in mouse fibrosarcoma, we used oxygen images obtained using pulse electron paramagnetic resonance pO2 imaging combined with 3D-printed radiation blocks. This achieved conformal radiation delivery to all hypoxic areas in FSa fibrosarcomas in mice. RESULTS We demonstrate that treatment delivering a radiation boost to hypoxic volumes has a significant (P = .04) doubling of tumor control relative to boosts to well-oxygenated volumes. Additional dose to well-oxygenated tumor regions minimally increases tumor control beyond the 15% control dose to the entire tumor. If we can identify portions of the tumor that are more resistant to radiation, it might be possible to reduce the dose to more sensitive tumor volumes without significant compromise in tumor control. CONCLUSIONS This work demonstrates in a single, intact mammalian tumor type that tumor hypoxia is a local tumor phenomenon whose treatment can be enhanced by local radiation. Despite enormous clinical effort to overcome hypoxic radiation resistance, to our knowledge this is the first such demonstration, even in preclinical models, of targeting additional radiation to hypoxic tumor to improve the therapeutic ratio.
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Affiliation(s)
- Boris Epel
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
| | - Matthew C Maggio
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
| | - Eugene D Barth
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
| | - Richard C Miller
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
| | - Charles A Pelizzari
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
| | - Martyna Krzykawska-Serda
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
| | - Subramanian V Sundramoorthy
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
| | - Bulent Aydogan
- Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
| | - Ralph R Weichselbaum
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois; Ludwig Center for Metastasis Research, University of Chicago, Chicago, Illinois
| | - Victor M Tormyshev
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Novosibirsk Institute of Organic Chemistry, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia
| | - Howard J Halpern
- National Institutes of Health Center for EPR Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
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23
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The Expanding Role of Physiologic Imaging in Radiation Oncology. Int J Radiat Oncol Biol Phys 2018; 102:694-697. [DOI: 10.1016/j.ijrobp.2018.01.059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 01/16/2018] [Indexed: 11/19/2022]
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24
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Hamming-Vrieze O, Navran A, Al-Mamgani A, Vogel WV. Biological PET-guided adaptive radiotherapy for dose escalation in head and neck cancer: a systematic review. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF RADIOPHARMACEUTICAL CHEMISTRY AND BIOLOGY 2018; 62:349-368. [DOI: 10.23736/s1824-4785.18.03087-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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25
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Kelada OJ, Decker RH, Nath SK, Johung KL, Zheng MQ, Huang Y, Gallezot JD, Liu C, Carson RE, Oelfke U, Carlson DJ. High Single Doses of Radiation May Induce Elevated Levels of Hypoxia in Early-Stage Non-Small Cell Lung Cancer Tumors. Int J Radiat Oncol Biol Phys 2018; 102:174-183. [PMID: 30102194 PMCID: PMC6092043 DOI: 10.1016/j.ijrobp.2018.05.032] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 05/10/2018] [Accepted: 05/13/2018] [Indexed: 01/12/2023]
Abstract
PURPOSE Tumor hypoxia correlates with treatment failure in patients undergoing conventional radiation therapy. However, no published studies have investigated tumor hypoxia in patients undergoing stereotactic body radiation therapy (SBRT). We aimed to noninvasively quantify the tumor hypoxic volume (HV) in non-small cell lung cancer (NSCLC) tumors to elucidate the potential role of tumor vascular response and reoxygenation at high single doses. METHODS AND MATERIALS Six SBRT-eligible patients with NSCLC tumors >1 cm were prospectively enrolled in an institutional review board-approved study. Dynamic positron emission tomography images were acquired at 0 to 120 minutes, 150 to 180 minutes, and 210 to 240 minutes after injection of 18F-fluoromisonidazole. Serial imaging was performed prior to delivery of 18 Gy and at approximately 48 hours and approximately 96 hours after SBRT. Tumor HVs were quantified using the tumor-to-blood ratio (>1.2) and rate of tracer influx (>0.0015 mL·min·cm-3). RESULTS An elevated and in some cases persistent level of tumor hypoxia was observed in 3 of 6 patients. Two patients exhibited no detectable baseline tumor hypoxia, and 1 patient with high baseline hypoxia only completed 1 imaging session. On the basis of the tumor-to-blood ratio, in the remaining 3 patients, tumor HVs increased on day 2 after 18 Gy and then showed variable responses on day 4. In the 3 of 6 patients with detectable hypoxia at baseline, baseline tumor HVs ranged between 17% and 24% (mean, 21%), and HVs on days 2 and 4 ranged between 33% and 45% (mean, 40%) and between 18% and 42% (mean, 28%), respectively. CONCLUSIONS High single doses of radiation delivered as part of SBRT may induce an elevated and in some cases persistent state of tumor hypoxia in NSCLC tumors. Hypoxia imaging with 18F-fluoromisonidazole positron emission tomography should be used in a larger cohort of NSCLC patients to determine whether elevated tumor hypoxia is predictive of treatment failure in SBRT.
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Affiliation(s)
- Olivia J Kelada
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut; Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany
| | - Roy H Decker
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut
| | - Sameer K Nath
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut
| | - Kimberly L Johung
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut
| | - Ming-Qiang Zheng
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
| | - Yiyun Huang
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
| | - Jean-Dominique Gallezot
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
| | - Chi Liu
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
| | - Richard E Carson
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
| | - Uwe Oelfke
- Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany
| | - David J Carlson
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
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26
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Stieb S, Eleftheriou A, Warnock G, Guckenberger M, Riesterer O. Longitudinal PET imaging of tumor hypoxia during the course of radiotherapy. Eur J Nucl Med Mol Imaging 2018; 45:2201-2217. [PMID: 30128659 DOI: 10.1007/s00259-018-4116-y] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 07/30/2018] [Indexed: 12/11/2022]
Abstract
Hypoxia results from an imbalance between oxygen supply and consumption. It is a common phenomenon in solid malignant tumors such as head and neck cancer. As hypoxic cells are more resistant to therapy, tumor hypoxia is an indicator for poor prognosis. Several techniques have been developed to measure tissue oxygenation. These are the Eppendorf O2 polarographic needle electrode, immunohistochemical analysis of endogenous (e.g., hypoxia-inducible factor-1α (HIF-1a)) and exogenous markers (e.g., pimonidazole) as well as imaging methods such as functional magnetic resonance imaging (e.g., blood oxygen level dependent (BOLD) imaging, T1-weighted imaging) and hypoxia positron emission tomography (PET). Among the imaging modalities, only PET is sufficiently validated to detect hypoxia for clinical use. Hypoxia PET tracers include 18F-fluoromisonidazole (FMISO), the most commonly used hypoxic marker, 18F-flouroazomycin arabinoside (FAZA), 18Ffluoroerythronitroimidazole (FETNIM), 18F-2-nitroimidazolpentafluoropropylacetamide (EF5) and 18F-flortanidazole (HX4). As technical development provides the opportunity to increase the radiation dose to subregions of the tumor, such as hypoxic areas, it has to be ensured that these regions are stable not only from imaging to treatment but also through the course of radiotherapy. The aim of this review is therefore to characterize the behavior of tumor hypoxia during radiotherapy for the whole tumor and for subregions by using hypoxia PET tracers, with focus on head and neck cancer patients.
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Affiliation(s)
- Sonja Stieb
- Department of Radiation Oncology, University Hospital and University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland. .,Institute of Diagnostic and Interventional Radiology, University Hospital and University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
| | - Afroditi Eleftheriou
- Department of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland
| | - Geoffrey Warnock
- Department of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.,Department of Nuclear Medicine, University Hospital and University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital and University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Oliver Riesterer
- Department of Radiation Oncology, University Hospital and University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
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27
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Kelada OJ, Rockwell S, Zheng MQ, Huang Y, Liu Y, Booth CJ, Decker RH, Oelfke U, Carson RE, Carlson DJ. Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [ 18F]Fluoromisonidazole ([ 18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements. Mol Imaging Biol 2018; 19:893-902. [PMID: 28409339 DOI: 10.1007/s11307-017-1083-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
PURPOSE The purpose of this study is to use dynamic [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) to compare estimates of tumor hypoxic fractions (HFs) derived by tracer kinetic modeling, tissue-to-blood ratios (TBR), and independent oxygen (pO2) measurements. PROCEDURES BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO2 measurements. Data from 120-min dynamic [18F]FMISO scans were fit to two-compartment irreversible three rate constant (K 1, k 2, k 3) and Patlak models (K i). Tumor HFs were calculated and compared using K i, k 3, TBR, and pO2 values. The clinical impact of each method was evaluated on [18F]FMISO scans for three non-small cell lung cancer (NSCLC) radiotherapy patients. RESULTS HFs defined by TBR (≥1.2, ≥1.3, and ≥1.4) ranged from 2 to 85 % of absolute tumor volume. HFs defined by K i (>0.004 ml min cm-3) and k 3 (>0.008 min-1) varied from 9 to 85 %. HF quantification was highly dependent on metric (TBR, k 3, or K i) and threshold. HFs quantified on human [18F]FMISO scans varied from 38 to 67, 0 to 14, and 0.1 to 27 %, for each patient, respectively, using TBR, k 3, and K i metrics. CONCLUSIONS [18F]FMISO PET imaging metric choice and threshold impacts hypoxia quantification reliability. Our results suggest that tracer kinetic modeling has the potential to improve hypoxia quantification clinically as it may provide a stronger correlation with direct pO2 measurements.
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Affiliation(s)
- Olivia J Kelada
- Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, CT, 06520-8040, USA.,Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany
| | - Sara Rockwell
- Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, CT, 06520-8040, USA.,Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA
| | - Ming-Qiang Zheng
- Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA
| | - Yiyun Huang
- Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA
| | - Yanfeng Liu
- Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, CT, 06520-8040, USA
| | - Carmen J Booth
- Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Roy H Decker
- Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, CT, 06520-8040, USA
| | - Uwe Oelfke
- Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany
| | - Richard E Carson
- Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA
| | - David J Carlson
- Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, CT, 06520-8040, USA.
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How Advances in Imaging Will Affect Precision Radiation Oncology. Int J Radiat Oncol Biol Phys 2018; 101:292-298. [DOI: 10.1016/j.ijrobp.2018.01.047] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 05/11/2017] [Accepted: 01/12/2018] [Indexed: 11/20/2022]
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Zhu T, Das S, Wong TZ. Integration of PET/MR Hybrid Imaging into Radiation Therapy Treatment. Magn Reson Imaging Clin N Am 2017; 25:377-430. [PMID: 28390536 DOI: 10.1016/j.mric.2017.01.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Hybrid PET/MR imaging is in early development for treatment planning. This article briefly reviews research and clinical applications of PET/MR imaging in radiation oncology. With improvements in workflow, more specific tracers, and fast and robust acquisition protocols, PET/MR imaging will play an increasingly important role in better target delineation for treatment planning and have clear advantages in the evaluation of tumor response and in a better understanding of tumor heterogeneity. With advances in treatment delivery and the potential of integrating PET/MR imaging with research on radiomics for radiation oncology, quantitative and physiologic information could lead to more precise and personalized RT.
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Affiliation(s)
- Tong Zhu
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA
| | - Shiva Das
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA
| | - Terence Z Wong
- Department of Radiology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA.
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Skorska M, Piotrowski T, Ryczkowski A. Comparison of dose distribution for head and neck cancer patients with and without dose painting escalation during radiotherapy realized with tomotherapy unit. Br J Radiol 2017; 90:20170019. [PMID: 28555505 DOI: 10.1259/bjr.20170019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE To determine and quantify the percentage dose increase to organs at risk (OARs) with multiple-level dose painting (DP) for patients with head and neck cancer in comparison with standard regimen. METHODS 12 patients who had undergone fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET)/CT scan were retrospectively enrolled. Two treatment plans-one using DP escalation and one without-were optimized for each patient base on PET/CT data. The following variables were assessed: dose to OARs and target volumes; execution time; equivalent uniform dose; and normal tissue complication probability. RESULTS No statistically significant differences in beam-on time were observed between plans with and without DP. However, significantly higher doses were observed for all DP-escalated plans in the OARs, with only two exceptions: the brain stem and V60Gy for the mandible. Multiple-level DP resulted in dose increases ranging from 3.0% to 12.9%, depending on the OAR. The largest increase was seen for the parotid glands and the smallest for the mandible. Significant differences in the equivalent uniform dose were observed only for the parotid glands and spinal column, where the dose without DP was lower. The normal tissue complication probability for most OARs was very small. CONCLUSION Importantly, even though DP escalation resulted in higher doses to OARs vs conventional treatment planning, these usually did not exceed the dose tolerance levels. However, clinical trials are necessary to confirm the benefits of DP and to guarantee no additional toxicity. Advances in knowledge: Multiple-level DP by numbers resulted in 3.0-12.9% dose increase, depending on the OAR. Our findings may suggest that DP escalation to very high doses is feasible for about 83% of patients without higher toxicity; however, it still should be confirmed on a larger group of patients.
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Affiliation(s)
- Malgorzata Skorska
- 1 Department of Medical Physics, Greater Poland Cancer Centre, Poznan, Poland
| | - Tomasz Piotrowski
- 1 Department of Medical Physics, Greater Poland Cancer Centre, Poznan, Poland.,2 Department of Electroradiology, University of Medical Sciences, Poznan, Poland
| | - Adam Ryczkowski
- 1 Department of Medical Physics, Greater Poland Cancer Centre, Poznan, Poland
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31
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Grimes DR, Warren DR, Warren S. Hypoxia imaging and radiotherapy: bridging the resolution gap. Br J Radiol 2017; 90:20160939. [PMID: 28540739 PMCID: PMC5603947 DOI: 10.1259/bjr.20160939] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Oxygen distribution is a major determinant of treatment success in radiotherapy, with well-oxygenated tumour regions responding by up to a factor of three relative to anoxic volumes. Conversely, tumour hypoxia is associated with treatment resistance and negative prognosis. Tumour oxygenation is highly heterogeneous and difficult to measure directly. The recent advent of functional hypoxia imaging modalities such as fluorine-18 fluoromisonidazole positron emission tomography have shown promise in non-invasively determining regions of low oxygen tension. This raises the prospect of selectively increasing dose to hypoxic subvolumes, a concept known as dose painting. Yet while this is a promising approach, oxygen-mediated radioresistance is inherently a multiscale problem, and there are still a number of substantial challenges that must be overcome if hypoxia dose painting is to be successfully implemented. Current imaging modalities are limited by the physics of such systems to have resolutions in the millimetre regime, whereas oxygen distribution varies over a micron scale, and treatment delivery is typically modulated on a centimetre scale. In this review, we examine the mechanistic basis and implications of the radiobiological oxygen effect, the factors influencing microscopic heterogeneity in tumour oxygenation and the consequent challenges in the interpretation of clinical hypoxia imaging (in particular fluorine-18 fluoromisonidazole positron emission tomography). We also discuss dose-painting approaches and outline challenges that must be addressed to improve this treatment paradigm.
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Affiliation(s)
- David Robert Grimes
- 1 Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratory, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford OX37DQ, UK.,2 Centre for Advanced and Interdisciplinary Radiation Research (CAIRR), School of Mathematics and Physics, Queen's University Belfast, UK
| | - Daniel R Warren
- 1 Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratory, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford OX37DQ, UK
| | - Samantha Warren
- 1 Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratory, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford OX37DQ, UK.,3 Hall-Edwards Radiotherapy Research Group, Queen Elizabeth Hospital, Birmingham, UK
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32
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Nohadani O, Roy A. Robust optimization with time-dependent uncertainty in radiation therapy. ACTA ACUST UNITED AC 2017. [DOI: 10.1080/24725579.2017.1296907] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Omid Nohadani
- Department of Industrial Engineering and Management Sciences, Northwestern University, Evanston, IL, USA
| | - Arkajyoti Roy
- Department of Industrial Engineering and Management Sciences, Northwestern University, Evanston, IL, USA
- Department of Applied Statistics and Operations Research, Bowling Green State University, Bowling Green, OH, USA
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Vera P, Thureau S, Chaumet-Riffaud P, Modzelewski R, Bohn P, Vermandel M, Hapdey S, Pallardy A, Mahé MA, Lacombe M, Boisselier P, Guillemard S, Olivier P, Beckendorf V, Salem N, Charrier N, Chajon E, Devillers A, Aide N, Danhier S, Denis F, Muratet JP, Martin E, Riedinger AB, Kolesnikov-Gauthier H, Dansin E, Massabeau C, Courbon F, Farcy Jacquet MP, Kotzki PO, Houzard C, Mornex F, Vervueren L, Paumier A, Fernandez P, Salaun M, Dubray B. Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by 18F-Misonidazole PET/CT in Patients with Non-Small Cell Lung Carcinoma (RTEP5 Study). J Nucl Med 2017; 58:1045-1053. [PMID: 28254869 DOI: 10.2967/jnumed.116.188367] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Accepted: 02/07/2017] [Indexed: 01/09/2023] Open
Abstract
See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant 18F-misonidazole (18F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The 18F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In 18F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-β = 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were 18F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the 18F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the 18F-FMISO-negative patients (P = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the 18F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Conclusion: Our approach results in a response rate of 40% or more, with acceptable toxicity. 18F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.
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Affiliation(s)
- Pierre Vera
- Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, University of Rouen, Rouen, France
| | - Sébastien Thureau
- Department of Radiation Oncology and Medical Physics, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, Rouen, France
| | - Philippe Chaumet-Riffaud
- Department of Nuclear Medicine, Hôpitaux universitaires Paris Sud Bicêtre AP-HP and University Paris Sud, Paris, France
| | - Romain Modzelewski
- Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, University of Rouen, Rouen, France
| | - Pierre Bohn
- Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, University of Rouen, Rouen, France
| | - Maximilien Vermandel
- University Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Image Assisted Laser Therapy for Oncology, Lille, France
| | - Sébastien Hapdey
- Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, University of Rouen, Rouen, France
| | - Amandine Pallardy
- Department of Nuclear Medicine, Nantes University Hospital, Nantes, France
| | - Marc-André Mahé
- Department of Radiation Oncology, Institut de Cancérologie de l'Ouest (ICO)-René Gauducheau, Nantes, France
| | - Marie Lacombe
- Department of Nuclear Medicine, Institut de Cancérologie de l'Ouest (ICO), Nantes, France
| | - Pierre Boisselier
- Department of Radiation Oncology, Institut régional du Cancer Montpellier (ICM), Montpellier, France
| | - Sophie Guillemard
- Department of Nuclear Medicine, Institut régional du Cancer Montpellier (ICM), Montpellier, France
| | - Pierre Olivier
- Department of Nuclear Medicine, Brabois University Hospital, Nancy, France
| | - Veronique Beckendorf
- Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy, France
| | - Naji Salem
- Department of Radiation Oncology, Institut Paoli Calmette, Marseille, France
| | - Nathalie Charrier
- Department of Nuclear Medicine, Institut Paoli Calmette, Marseille, France
| | - Enrique Chajon
- Department of Radiation Oncology, Centre regional de lutte contre le cancer de Bretagne Eugène Marquis, Rennes, France
| | - Anne Devillers
- Department of Nuclear Medicine, Centre regional de lutte contre le cancer de Bretagne Eugène Marquis, Rennes, France
| | - Nicolas Aide
- Nicolas Aide, Nuclear Medicine and TEP Centre, Caen University Hospital and Inserm U1086 ANTICIPE, Caen, France
| | - Serge Danhier
- Department of Radiation Oncology, François Baclesse Cancer Center, Caen, France
| | - Fabrice Denis
- Department of Radiation Oncology, Institut Inter-Régional de Cancérologie (ILC), Centre Jean Bernard/Clinique Victor Hugo, Le Mans, France
| | - Jean-Pierre Muratet
- Department of Nuclear Medicine, Institut Inter-Régional de Cancérologie (ILC), Centre Jean Bernard/Clinique Victor Hugo, Le Mans, France
| | - Etienne Martin
- Radiation Oncology, Centre Georges-Francois Leclerc, Dijon, France
| | | | | | - Eric Dansin
- Department of Radiation Oncology, Oscar Lambret Center, Lille cedex, France
| | - Carole Massabeau
- Département de Radiothérapie. Institut Universitaire du Cancer, Toulouse cedex 9, France
| | - Fredéric Courbon
- Department of Nuclear Medicine, Institut Claudius Regaud, IUCT, Toulouse cedex 9, France
| | - Marie-Pierre Farcy Jacquet
- Department of Radiation Oncology, CHU de Nîmes, Institut de cancérologie du Gard, Rue Henri Pujol, Nîmes, France
| | - Pierre-Olivier Kotzki
- Department of Nuclear Medicine, Institut régional du Cancer Montpellier (ICM), Montpellier, France.,Department of Nuclear Medicine, CHU de Nîmes, Institut de cancérologie du Gard, Nîmes, France
| | - Claire Houzard
- Department of Nuclear Medicine, Hospices Civils de Lyon, Lyon, France
| | - Francoise Mornex
- Department of Radiation Oncology, Hospices Civils de Lyon, Lyon, France
| | | | - Amaury Paumier
- Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, site Paul Papin, France
| | - Philippe Fernandez
- Department of Nuclear Medicine, Hôpital Pellegrin, CHU de Bordeaux, France; and
| | - Mathieu Salaun
- Normandy University, UNIROUEN, QuantIF-LITIS EA 4108, Rouen University Hospital, Department of Pulmonology-Thoracic Oncology-Respiratory Intensive Care, Rouen, France
| | - Bernard Dubray
- Department of Radiation Oncology and Medical Physics, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, Rouen, France
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Pigorsch SU, Wilkens JJ, Kampfer S, Kehl V, Hapfelmeier A, Schläger C, Bier H, Schwaiger M, Combs SE. Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol. Radiat Oncol 2017; 12:45. [PMID: 28249612 PMCID: PMC5333380 DOI: 10.1186/s13014-017-0776-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 02/06/2017] [Indexed: 11/16/2022] Open
Abstract
Background Standard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation. Methods The ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1st and 5th week (cisplatin 20 mg/m2/d d 1–5 and d 29–33) or weekly (cisplatin 40 mg/m2/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start. Discussion The primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1. Trial registration ClinicalTrials.gov Identifier: NCT 01212354, EudraCT-No.: 2010-021139-15
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Affiliation(s)
- Steffi U Pigorsch
- Department of Radiaton Oncology, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany. .,Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, D-85764, Oberschleissheim, Germany.
| | - Jan J Wilkens
- Department of Radiaton Oncology, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.,Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, D-85764, Oberschleissheim, Germany
| | - Severin Kampfer
- Department of Radiaton Oncology, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.,Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, D-85764, Oberschleissheim, Germany
| | - Victoria Kehl
- Institute of Medical Statistics and Epidemiology (IMSE), Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany
| | - Alexander Hapfelmeier
- Institute of Medical Statistics and Epidemiology (IMSE), Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany
| | - Christian Schläger
- Münchner Studienzentrum (MSZ Coordination Centre for Clinical Trials), Technical University of Munich, Ismaninger Strasse 22, D-81675, Munich, Germany
| | - Henning Bier
- Department of Ear, Neck and Throat (ENT), Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany
| | - Markus Schwaiger
- Department of Nuclear Medicine, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany
| | - Stephanie E Combs
- Department of Radiaton Oncology, Technical University of Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675, Munich, Germany.,Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, D-85764, Oberschleissheim, Germany
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Hong BJ, Kim J, Jeong H, Bok S, Kim YE, Ahn GO. Tumor hypoxia and reoxygenation: the yin and yang for radiotherapy. Radiat Oncol J 2016; 34:239-249. [PMID: 28030900 PMCID: PMC5207368 DOI: 10.3857/roj.2016.02012] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 12/11/2016] [Accepted: 12/12/2016] [Indexed: 12/22/2022] Open
Abstract
Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of ‘reoxygenation’ phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because ‘reoxygenation’ is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn’t it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.
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Affiliation(s)
- Beom-Ju Hong
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
| | - Jeongwoo Kim
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
| | - Hoibin Jeong
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
| | - Seoyeon Bok
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
| | - Young-Eun Kim
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
| | - G-One Ahn
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
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36
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Jeong H, Bok S, Hong BJ, Choi HS, Ahn GO. Radiation-induced immune responses: mechanisms and therapeutic perspectives. Blood Res 2016; 51:157-163. [PMID: 27722125 PMCID: PMC5054246 DOI: 10.5045/br.2016.51.3.157] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Revised: 09/13/2016] [Accepted: 09/13/2016] [Indexed: 01/22/2023] Open
Abstract
Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then discuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radiotherapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.
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Affiliation(s)
- Hoibin Jeong
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Korea
| | - Seoyeon Bok
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Korea
| | - Beom-Ju Hong
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Korea
| | - Hyung-Seok Choi
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Korea
| | - G-One Ahn
- Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Korea
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37
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Quartuccio N, Caobelli F, Di Mauro F, Cammaroto G. Non-18F-FDG PET/CT in the management of patients affected by HNC: state-of-the-art. Nucl Med Commun 2016; 37:891-898. [PMID: 27139114 DOI: 10.1097/mnm.0000000000000530] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PET/computed tomography with F-fluorodeoxyglucose is considered a powerful molecular imaging technique that can provide useful information in the management of patients affected by head and neck cancer. However, misleading findings have been reported because of nonspecific uptake caused by peritumoural inflammation and physiologic changes in nonmalignant tissues in the head and neck region. More specific β-emitting tracers have been introduced that can track other pathological processes. We aimed to review the existing literature performing the search until June 2015 on non-F-fluorodeoxyglucose PET tracers in head and neck cancer to highlight their role in clinical practice.
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Affiliation(s)
- Natale Quartuccio
- aWolfson Molecular Imaging Centre, University of Manchester, Manchester, UK bDepartment of Nuclear Medicine, Hannover Medical School, Hanover, Germany cDepartment of Nuclear Medicine, Universitätsspital Basel, Basel, Switzerland dNuclear Medicine Unit, Department of Biomedical Sciences and Morphologic and Functional Images eDepartment of Otorhinolaryngology, University of Messina, Messina fYoung Executive Committee of the Italian Association of Nuclear Medicine (AIMN), Milan, Italy
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Wanek T, Kreis K, Križková P, Schweifer A, Denk C, Stanek J, Mairinger S, Filip T, Sauberer M, Edelhofer P, Traxl A, Muchitsch VE, Mereiter K, Hammerschmidt F, Cass CE, Damaraju VL, Langer O, Kuntner C. Synthesis and preclinical characterization of 1-(6'-deoxy-6'-[ 18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6'-[ 18F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia. Bioorg Med Chem 2016; 24:5326-5339. [PMID: 27614920 DOI: 10.1016/j.bmc.2016.08.053] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 08/16/2016] [Accepted: 08/27/2016] [Indexed: 12/31/2022]
Abstract
Positron emission tomography (PET) using fluorine-18 (18F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6'-deoxy-6'-[18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[18F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [18F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12±8% (n=10, based on [18F]fluoride starting activity) in a total synthesis time of 60min with a specific activity at end of synthesis of 218±58GBq/μmol (n=10). Both radiolabeling precursor β-6 and unlabeled reference compound β-1 were prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-α-d-allofuranose. In vitro experiments demonstrated an interaction of β-1 with SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific retention of β-[18F]1 in tumor cell lines. In biodistribution studies in healthy mice β-[18F]1 showed homogenous tissue distribution and excellent metabolic stability, which was unaffected by tissue oxygenation. PET studies in tumor bearing mice showed tumor-to-muscle ratios of 2.13±0.22 (n=4) at 2h after administration of β-[18F]1. In ex vivo autoradiography experiments β-[18F]1 distribution closely matched staining with the hypoxia marker pimonidazole. In conclusion, β-[18F]1 shows potential as PET hypoxia radiotracer which merits further investigation.
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Affiliation(s)
- Thomas Wanek
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria.
| | - Katharina Kreis
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
| | - Petra Križková
- Institute of Organic Chemistry, University of Vienna, Währingerstraße 38, A-1090 Vienna, Austria
| | - Anna Schweifer
- Institute of Organic Chemistry, University of Vienna, Währingerstraße 38, A-1090 Vienna, Austria
| | - Christoph Denk
- Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163, A-1060 Vienna, Austria
| | - Johann Stanek
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
| | - Severin Mairinger
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
| | - Thomas Filip
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
| | - Michael Sauberer
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
| | - Patricia Edelhofer
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
| | - Alexander Traxl
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
| | - Viktoria E Muchitsch
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
| | - Kurt Mereiter
- Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/164, A-1060 Vienna, Austria
| | - Friedrich Hammerschmidt
- Institute of Organic Chemistry, University of Vienna, Währingerstraße 38, A-1090 Vienna, Austria
| | - Carol E Cass
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
| | - Vijaya L Damaraju
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
| | - Oliver Langer
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria; Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria
| | - Claudia Kuntner
- Biomedical Systems, AIT Austrian Institute of Technology GmbH, A-2444 Seibersdorf, Austria
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Yuan LW, Yamashita H, Seto Y. Glucose metabolism in gastric cancer: The cutting-edge. World J Gastroenterol 2016; 22:2046-2059. [PMID: 26877609 PMCID: PMC4726677 DOI: 10.3748/wjg.v22.i6.2046] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Revised: 09/18/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer.
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Sharma P, Mukherjee A. Newer positron emission tomography radiopharmaceuticals for radiotherapy planning: an overview. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:53. [PMID: 26904575 PMCID: PMC4739998 DOI: 10.3978/j.issn.2305-5839.2016.01.26] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/28/2015] [Accepted: 12/17/2015] [Indexed: 01/30/2023]
Abstract
Positron emission tomography-computed tomography (PET-CT) has changed cancer imaging in the last decade, for better. It can be employed for radiation treatment planning of different cancers with improved accuracy and outcomes as compared to conventional imaging methods. (18)F-fluorodeoxyglucose remains the most widely used though relatively non-specific cancer imaging PET tracer. A wide array of newer PET radiopharmaceuticals has been developed for targeted imaging of different cancers. PET-CT with such new PET radiopharmaceuticals has also been used for radiotherapy planning with encouraging results. In the present review we have briefly outlined the role of PET-CT with newer radiopharmaceuticals for radiotherapy planning and briefly reviewed the available literature in this regard.
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Chirla R, Marcu LG. PET-based quantification of statistical properties of hypoxic tumor subvolumes in head and neck cancer. Phys Med 2016; 32:23-35. [DOI: 10.1016/j.ejmp.2015.12.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 11/29/2015] [Accepted: 12/13/2015] [Indexed: 11/30/2022] Open
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Tamaki N, Hirata K. Tumor hypoxia: a new PET imaging biomarker in clinical oncology. Int J Clin Oncol 2015; 21:619-625. [DOI: 10.1007/s10147-015-0920-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 10/20/2015] [Indexed: 01/02/2023]
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Zheng J, Klinz SG, De Souza R, Fitzgerald J, Jaffray DA. Longitudinal tumor hypoxia imaging with [(18)F]FAZA-PET provides early prediction of nanoliposomal irinotecan (nal-IRI) treatment activity. EJNMMI Res 2015; 5:57. [PMID: 26481012 PMCID: PMC4610963 DOI: 10.1186/s13550-015-0135-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Accepted: 10/09/2015] [Indexed: 02/05/2023] Open
Abstract
Background Non-invasive measurement of tumor hypoxia has demonstrated potential for the evaluation of disease progression, as well as prediction and assessment of treatment outcome. [18F]fluoroazomycin arabinoside (FAZA) positron emission tomography (PET) has been identified as a robust method for quantification of hypoxia both preclinically and clinically. The goal of this investigation was to evaluate the feasibility and value of repeated FAZA-PET imaging to quantify hypoxia in tumors that received multi-dose chemotherapy. Methods FAZA-PET imaging was conducted over a 21-day period in a mouse xenograft model of HT-29 human colorectal carcinoma, following multi-dose chemotherapy treatment with irinotecan (CPT-11) or nanoliposomal irinotecan (nal-IRI, MM-398). Results Tumors treated with 10 mg/kg nal-IRI maintained significantly lower levels of hypoxia and smaller hypoxic fractions compared to tumors that received 50 mg/kg CPT-11. Specifically, differences in FAZA uptake were detectable 9 days before any significant differences in tumor volume were observed between the treatment groups. Conclusions These findings highlight the potential use of FAZA-PET as an early marker of treatment response following multi-dose chemotherapy. Electronic supplementary material The online version of this article (doi:10.1186/s13550-015-0135-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jinzi Zheng
- TECHNA Institute for the Advancement of Technology for Health, University Health Network, 101 College Street, Rm 7-302, Toronto, Ontario, M5G 1L7, Canada. .,Department of Radiation Physics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. .,Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
| | | | - Raquel De Souza
- Department of Radiation Physics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | | | - David A Jaffray
- TECHNA Institute for the Advancement of Technology for Health, University Health Network, 101 College Street, Rm 7-302, Toronto, Ontario, M5G 1L7, Canada.,Department of Radiation Physics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.,Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.,Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
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Rasmussen JH, Vogelius IR, Aznar MC, Fischer BM, Christensen CB, Friborg J, Loft A, Kristensen CA, Bentzen SM, Specht L. Spatio-temporal stability of pre-treatment 18F-Fludeoxyglucose uptake in head and neck squamous cell carcinomas sufficient for dose painting. Acta Oncol 2015; 54:1416-22. [PMID: 26343280 DOI: 10.3109/0284186x.2015.1061694] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND The pre-treatment 18F-Fludeoxyglucose (FDG) avid subvolume of the tumor has shown promise as a potential target for dose painting in patients with in head and neck squamous cell carcinomas (HNSCC). PURPOSE The purposes of this study are: 1) to assess the pre-treatment spatio-temporal variability of FDG PET/CT target volumes and 2) to assess the impact of this variability on dose distribution in dose painting plans in patients with HNSCC. MATERIAL AND METHODS Thirty patients were enrolled and scanned twice, three days apart, days prior to treatment. Delineation of the FDG avid subvolume of the tumor and lymph nodes on both scans was performed by a specialist in nuclear medicine yielding GTVPET1 and GTVPET2 and segmentation based on SUV iso-contours were constructed yielding two metabolic target volumes, MTV1 and MTV2. Images were co-registered rigidly and dose painting plans with dose escalation up to 82 Gy to GTVPET1 were planned and GTVPET2 was copied from the co-registered images to the dose planning scan. Variation in dose to the target and modeled tumor control probability were assessed as measures of the impact of imaging variations in a dose painting scenario. RESULTS Twenty-four patients were available for full analysis. The median mismatch between GTVPET1 and GTVPET2 was 14.2% (1.7 cm(3)). The median difference in dose to the FDG planning target volume was 0.3 Gy (PTVPET) and 0.4 Gy (PTVMTV). Median difference in the modeled tumor control probability (TCP) was < 0.2% and 23 of 24 patients had a difference in expected TCP < 1%. CONCLUSIONS Pre-treatment FDG PET/CT target volumes were stable and day-to-day variability had no relevant impact on dose distribution and expected tumor control in dose painting plans.
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Affiliation(s)
- Jacob H Rasmussen
- a Department of Oncology , Section of Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark
| | - Ivan R Vogelius
- a Department of Oncology , Section of Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark
| | - Marianne C Aznar
- a Department of Oncology , Section of Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark
| | - Barbara M Fischer
- b Department of Clinical Physiology , Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen , Denmark
| | - Charlotte B Christensen
- b Department of Clinical Physiology , Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen , Denmark
| | - Jeppe Friborg
- a Department of Oncology , Section of Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark
| | - Annika Loft
- b Department of Clinical Physiology , Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen , Denmark
| | - Claus A Kristensen
- a Department of Oncology , Section of Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark
| | - Søren M Bentzen
- c Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center , and Department of Epidemiology and Public Health , University of Maryland School of Medicine , Baltimore , USA
| | - Lena Specht
- a Department of Oncology , Section of Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark
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Even AJ, van der Stoep J, Zegers CM, Reymen B, Troost EG, Lambin P, van Elmpt W. PET-based dose painting in non-small cell lung cancer: Comparing uniform dose escalation with boosting hypoxic and metabolically active sub-volumes. Radiother Oncol 2015; 116:281-6. [DOI: 10.1016/j.radonc.2015.07.013] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Revised: 07/03/2015] [Accepted: 07/16/2015] [Indexed: 12/22/2022]
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Biau J, Chautard E, Miroir J, Lapeyre M. [Radioresistance parameters in head and neck cancers and methods to radiosensitize]. Cancer Radiother 2015; 19:337-46; quiz 360-1, 363. [PMID: 26119219 DOI: 10.1016/j.canrad.2015.02.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 02/06/2015] [Accepted: 02/12/2015] [Indexed: 12/24/2022]
Abstract
Head and neck cancers have been widely studied concerning their sensitivity to radiation therapy. Several parameters affect tumour response to radiation therapy. Some parameters are linked to the tumour. Large or invasive tumours, localization, such as oral cavity or adenopathy, are factors of radioresistance. Others parameters are linked to the patients themselves. Tobacco intoxication during radiotherapy and a low hemoglobin level contribute to radioresistance. More recently, a positive human papilloma virus (HPV) status has been reported to positively affect radiosensitivity. Finally, other parameters are related to tumour biology. Hypoxia, intrinsic radiosensitivity of tumour cells, tumour differentiation and repopulation (provided by Ki-67 index or EGFR level) are components of radiosensitivity. Currently, concurrent chemoradiotherapy is one of the gold standard treatments to overcome clinical outcome of locally advanced head and neck cancer. This combination increases locoregional control and survival. Taxane-based induction chemotherapy can also be an alternative. Another validated approach is the association of radiotherapy with cetuximab (EGFR targeting) but only one randomized study has been published. Fractionation modifications, especially hyperfractionation, have given positive results on both tumour control and survival. Strategies targeting hypoxia improve locoregional control but have less clinical impact.
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Affiliation(s)
- J Biau
- Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 5026, 63011 Clermont-Ferrand cedex 1, France; EA7283 Cancer Resistance Exploring and Targeting (CREAT), Clermont université, université d'Auvergne, 49, boulevard François-Mitterrand, CS 60032, 63001 Clermont-Ferrand cedex 1, France; Équipe recombinaison, réparation et cancer, UMR 3347, CNRS, centre universitaire, 91405 Orsay cedex, France; Inserm U1021, centre universitaire, 91405 Orsay cedex, France; Institut Curie, 26, rue d'Ulm, 75005 Paris, France.
| | - E Chautard
- Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 5026, 63011 Clermont-Ferrand cedex 1, France; EA7283 Cancer Resistance Exploring and Targeting (CREAT), Clermont université, université d'Auvergne, 49, boulevard François-Mitterrand, CS 60032, 63001 Clermont-Ferrand cedex 1, France
| | - J Miroir
- Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 5026, 63011 Clermont-Ferrand cedex 1, France
| | - M Lapeyre
- Département de radiothérapie, centre Jean-Perrin, 58, rue Montalembert, BP 5026, 63011 Clermont-Ferrand cedex 1, France
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Arvold ND, Heidari P, Kunawudhi A, Sequist LV, Mahmood U. Tumor Hypoxia Response After Targeted Therapy in EGFR-Mutant Non-Small Cell Lung Cancer: Proof of Concept for FMISO-PET. Technol Cancer Res Treat 2015; 15:234-42. [PMID: 25759424 DOI: 10.1177/1533034615574386] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Accepted: 01/28/2015] [Indexed: 01/14/2023] Open
Abstract
Hypoxia is associated with resistance to radiotherapy and chemotherapy. Functional imaging of hypoxia in non-small cell lung cancer (NSCLC) could allow early assessment of tumor response and guide subsequent therapies. Epidermal growth factor receptor (EGFR) inhibition with erlotinib reduces hypoxia in vivo. [18F]-Fluoromisonidazole (FMISO) is a radiolabeled tracer that selectively accumulates in hypoxic cells. We sought to determine whether FMISO positron emission tomography (FMISO-PET) could detect changes in hypoxia in vivo in response to EGFR-targeted therapy. In a preclinical investigation, nude mice with human EGFR-mutant lung adenocarcinoma xenografts underwent FMISO-PET scans before and 5 days after erlotinib or empty vehicle initiation. Descriptive statistics and analysis of variance (ANOVA) tests were used to analyze changes in standardized uptake value (SUV), with pooled analyses for the mice in each group (baseline, postvehicle, and posterlotinib). In a small correlative pilot human study, patients with EGFR-mutant metastatic NSCLC underwent FMISO-PET scans before and 10 to 12 days after erlotinib initiation. Changes in SUV were compared to standard chest computed tomography (CT) scans performed 6 weeks after erlotinib initiation. The mean (±standard error of the mean; SUVmean) of the xenografts was 0.17 ± 0.014, 0.14 ± 0.008, and 0.06 ± 0.004 for baseline, postvehicle, and posterlotinib groups, respectively, with lower SUVmean among the posterlotinib group compared to other groups (P < .05). Changes on preclinical PET imaging were striking, with near-complete disappearance of FMISO uptake after erlotinib initiation. Two patients were enrolled on the pilot study. In the first patient, SUVmean increased by 21% after erlotinib, with progression on 6-week chest CT followed by death after 4.8 months. In the second patient, SUVmean decreased by 7% after erlotinib, with regression on 6-week chest CT accompanied by clinical improvement; the patient had stable disease at 14.5 months. In conclusion, we observed that FMISO-PET can detect changes in hypoxia levels after EGFR-directed therapy in EGFR-mutant NSCLC. Further study is warranted to determine its utility as an imaging biomarker of early response to EGFR-directed therapy.
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Affiliation(s)
- Nils D Arvold
- Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, MA, USA
| | - Pedram Heidari
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
| | - Anchisa Kunawudhi
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
| | - Lecia V Sequist
- Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Umar Mahmood
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
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Cheney MD, Chen YL, Lim R, Winrich BK, Grosu AL, Trofimov AV, Depauw N, Shih HA, Schwab JH, Hornicek FJ, DeLaney TF. [18F]-Fluoromisonidazole positron emission tomography/computed tomography visualization of tumor hypoxia in patients with chordoma of the mobile and sacrococcygeal spine. Int J Radiat Oncol Biol Phys 2015; 90:1030-6. [PMID: 25539367 DOI: 10.1016/j.ijrobp.2014.08.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Revised: 08/05/2014] [Accepted: 08/13/2014] [Indexed: 01/15/2023]
Abstract
PURPOSE To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. METHODS AND MATERIALS A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs. RESULTS The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm(3)) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm(3) vs 63.4 cm(3); P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs. CONCLUSIONS Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted.
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Affiliation(s)
| | - Yen-Lin Chen
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Ruth Lim
- Department of Diagnostic Radiology, Massachusetts General Hospital, Boston, Massachusetts
| | - Barbara K Winrich
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Anca L Grosu
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Alexei V Trofimov
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Nicolas Depauw
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts; Centre of Medical Radiation Physics, University of Wollongong, Wollongong, NSW, Australia
| | - Helen A Shih
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Joseph H Schwab
- Department of Orthopedic Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Francis J Hornicek
- Department of Orthopedic Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Thomas F DeLaney
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
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Verwer EE, Boellaard R, Veldt AAMVD. Positron emission tomography to assess hypoxia and perfusion in lung cancer. World J Clin Oncol 2014; 5:824-844. [PMID: 25493221 PMCID: PMC4259945 DOI: 10.5306/wjco.v5.i5.824] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 04/29/2014] [Accepted: 07/15/2014] [Indexed: 02/06/2023] Open
Abstract
In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed.
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