Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Study protocol

Prospective, longitudinal, multi-modal functional imaging for radical chemo-IMRT treatment of locally advanced head and neck cancer: the INSIGHT study

Authors: Liam Welsh, Rafal Panek, Dualta McQuaid, Alex Dunlop, Maria Schmidt, Angela Riddell, Dow-Mu Koh, Simon Doran, Iain Murray, Yong Du, Sue Chua, Vibeke Hansen, Kee H. Wong, Jamie Dean, Sarah Gulliford, Shreerang Bhide, Martin O. Leach, Christopher Nutting, Kevin Harrington, Kate Newbold

Published in: Radiation Oncology | Issue 1/2015

Login to get access

Abstract

Background

Radical chemo-radiotherapy (CRT) is an effective organ-sparing treatment option for patients with locally advanced head and neck cancer (LAHNC). Despite advances in treatment for LAHNC, a significant minority of these patients continue to fail to achieve complete response with standard CRT. By constructing a multi-modality functional imaging (FI) predictive biomarker for CRT outcome for patients with LAHNC we hope to be able to reliably identify those patients at high risk of failing standard CRT. Such a biomarker would in future enable CRT to be tailored to the specific biological characteristics of each patients’ tumour, potentially leading to improved treatment outcomes.

Methods/design

The INSIGHT study is a single-centre, prospective, longitudinal multi-modality imaging study using functional MRI and FDG-PET/CT for patients with LAHNC squamous cell carcinomas receiving radical CRT. Two cohorts of patients are being recruited: one treated with, and another treated without, induction chemotherapy. All patients receive radical intensity modulated radiotherapy with concurrent chemotherapy. Patients undergo functional imaging before, during and 3 months after completion of radiotherapy, as well as at the time of relapse, should that occur within the first two years after treatment. Serum samples are collected from patients at the same time points as the FI scans for analysis of a panel of serum markers of tumour hypoxia.

Discussion

The primary aim of the INSIGHT study is to acquire a prospective multi-parametric longitudinal data set comprising functional MRI, FDG PET/CT, and serum biomarker data from patients with LAHNC undergoing primary radical CRT. This data set will be used to construct a predictive imaging biomarker for outcome after CRT for LAHNC. This predictive imaging biomarker will be used in future studies of functional imaging based treatment stratification for patients with LAHNC. Additional objectives are: defining the reproducibility of FI parameters; determining robust methods for defining FI based biological target volumes for IMRT planning; creation of a searchable database of functional imaging data for data mining. The INSIGHT study will help to establish the role of FI in the clinical management of LAHNC.

Trial registration

Literature
1.
Corvò R. Evidence-based radiation oncology in head and neck squamous cell carcinoma. Radiother Oncol. 2007;85:156–70.PubMedCrossRef
2.
Lefebvre JL, Ang KK, Larynx Preservation Consensus Panel. Larynx preservation clinical trial design: key issues and recommendations-a consensus panel summary. In Int J Radiat Oncol Biol Phys. 2009;73:1293–303.CrossRef
3.
Kazi R, Venkitaraman R, Johnson C, Prasad V, Clarke P, Rhys-Evans P, et al. Electroglottographic comparison of voice outcomes in patients with advanced laryngopharyngeal cancer treated by chemoradiotherapy or total laryngectomy. Int J Radiat Oncol Biol Phys. 2008;70:344–52.PubMedCrossRef
4.
Harrington KJ, Nutting CM. Interactions between ionizing radiation and drugs in head and neck cancer: how can we maximize the therapeutic index? Curr Opin Investig Drugs. 2002;3:807–11.PubMed
5.
Bentzen SM, Trotti A. Evaluation of early and late toxicities in chemoradiation trials. J Clin Oncol. 2007;25:4096–103.PubMedCrossRef
6.
Hunter KU, Schipper M, Feng FY, Lyden T, Haxer M, Murdoch-Kinch C-A, et al. Toxicities affecting quality of life after chemo-IMRT of oropharyngeal cancer: prospective study of patient-reported, observer-rated, and objective outcomes. Int J Radiat Oncol Biol Phys. 2013;85:935–40.PubMedCentralPubMedCrossRef
7.
Bhide SA, Newbold KL, Harrington KJ, Nutting CM. Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers. Br J Radiol. 2012;85:487–94.PubMedCentralPubMedCrossRef
8.
Grégoire V, Jeraj R, Lee JA, O’Sullivan B. Radiotherapy for head and neck tumours in 2012 and beyond: conformal, tailored, and adaptive? Lancet Oncol. 2012;13:e292–300.PubMedCrossRef
9.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.PubMedCentralPubMedCrossRef
10.
Clark GM. Prognostic factors versus predictive factors: Examples from a clinical trial of erlotinib. Mol Oncol. 2008;1:406–12.PubMedCrossRef
11.
Bachtiary B, Boutros PC, Pintilie M, Shi W, Bastianutto C, Li J-H, et al. Gene expression profiling in cervical cancer: an exploration of intratumor heterogeneity. Clin Cancer Res. 2006;12:5632–40.PubMedCrossRef
12.
Geißler C, Hambek M, Leinung M, Diensthuber M, Gassner D, Stöver T, et al. The challenge of tumor heterogeneity–different phenotypes of cancer stem cells in a head and neck squamous cell carcinoma xenograft mouse model. In Vivo. 2012;26:593–8.PubMed
13.
Harrington K, Jankowska P, Hingorani M. Molecular biology for the radiation oncologist: the 5Rs of radiobiology meet the hallmarks of cancer. Clin Oncol (R Coll Radiol). 2007;19:561–71.CrossRef
14.
Quon H, Brizel DM. Predictive and prognostic role of functional imaging of head and neck squamous cell carcinomas. Semin Radiat Oncol. 2012;22:220–32.PubMedCrossRef
15.
Ling CC, Humm J, Larson S, Amols H, Fuks Z, Leibel S, et al. Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Radiat Oncol Biol. 2000;47:551–60.CrossRef
16.
Horsman MR, Mortensen LS, Petersen JB, Busk M, Overgaard J. Imaging hypoxia to improve radiotherapy outcome. Nat Rev Clin Oncol. 2012;9:674–87.PubMedCrossRef
17.
van der Heide UA, Houweling AC, Groenendaal G, Beets-Tan RGH, Lambin P. Functional MRI for radiotherapy dose painting. Magn Reson Imaging. 2012;30:1216–23.PubMedCrossRef
18.
Schwartz DL, Rajendran J, Yueh B, Coltrera MD, Leblanc M, Eary J, et al. FDG-PET prediction of head and neck squamous cell cancer outcomes. Arch Otolaryngol Head Neck Surg. 2004;130:1361–7.PubMedCrossRef
19.
Cao Y, Popovtzer A, Li D, Chepeha DB, Moyer JS, Prince ME, et al. Early prediction of outcome in advanced head-and-neck cancer based on tumor blood volume alterations during therapy: a prospective study. Int J Radiat Oncol Biol Phys. 2008;72:1287–90.PubMedCentralPubMedCrossRef
20.
Galbán CJ, Mukherji SK, Chenevert TL, Meyer CR, Hamstra DA, Bland PH, et al. A feasibility study of parametric response map analysis of diffusion-weighted magnetic resonance imaging scans of head and neck cancer patients for providing early detection of therapeutic efficacy. Transl Oncol. 2009;2:184–90.PubMedCentralPubMedCrossRef
21.
Zips D, Zöphel K, Abolmaali N, Perrin R, Abramyuk A, Haase R, et al. Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer. Radiother Oncol. 2012;105:21–8.PubMedCrossRef
22.
Srinivasan A, Mohan S, Mukherji SK. Biologic imaging of head and neck cancer: the present and the future. AJNR Am J Neuroradiol. 2012;33:586–94.PubMedCrossRef
23.
Schwartz J, Humm JL, Gonen M, Kalaigian H, Schoder H, Larson SM, et al. Repeatability of SUV measurements in serial PET. Med Phys. 2011;38:2629–38.PubMedCrossRef
24.
Lambin P, van Stiphout RGPM, Starmans MHW, Rios-Velazquez E, Nalbantov G, Aerts HJWL, et al. Predicting outcomes in radiation oncology–multifactorial decision support systems. Nat Rev Clin Oncol. 2013;10:27–40.PubMedCrossRef
25.
Alber M, Thorwarth D. Multi-modality functional image guided dose escalation in the presence of uncertainties. Radiother Oncol. 2014.
26.
Boeckx C, Baay M, Wouters A, Specenier P, Vermorken JB, Peeters M, et al. Anti-epidermal growth factor receptor therapy in head and neck squamous cell carcinoma: focus on potential molecular mechanisms of drug resistance. Oncologist. 2013;18:850–64.PubMedCentralPubMedCrossRef
27.
Vermorken JB, Stöhlmacher-Williams J, Davidenko I, Licitra L, Winquist E, Villanueva C, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013;14:697–710.PubMedCrossRef
28.
29.
Nowsheen S, Bonner JA, Yang ES. The poly(ADP-Ribose) polymerase inhibitor ABT-888 reduces radiation-induced nuclear EGFR and augments head and neck tumor response to radiotherapy. Radiother Oncol. 2011;99:331–8.PubMedCentralPubMedCrossRef
30.
Forster M, Mendes R, Fedele S. Synthetic lethality and PARP-inhibitors in oral and head and neck cancer. Curr Pharm Des. 2012;18:5431–41.PubMedCrossRef
31.
Güster JD, Weissleder SV, Busch C-J, Kriegs M, Petersen C, Knecht R, et al. The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines. Radiother Oncol. 2014;113:345–51.PubMedCrossRef
32.
Masterson L, Moualed D, Liu ZW, Howard JEF, Dwivedi RC, Tysome JR, et al. De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials. Eur J Cancer. 2014;50:2636–48.PubMedCrossRef
33.
Rios-Velazquez E, Hoebers F, Aerts HJWL, Rietbergen MM, Brakenhoff RH, Leemans RC, et al. Externally validated HPV-based prognostic nomogram for oropharyngeal carcinoma patients yields more accurate predictions than TNM staging. Radiother Oncol. 2014;113:324–30.PubMedCrossRef
34.
Bhide SA, Davies M, Burke K, McNair HA, Hansen V, Barbachano Y, et al. Weekly volume and dosimetric changes during chemoradiotherapy with intensity-modulated radiation therapy for head and neck cancer: a prospective observational study. Int J Radiat Oncol Biol Phys. 2010;76:1360–8.PubMedCrossRef
35.
Powell C, Schmidt M, Borri M, Koh D-M, Partridge M, Riddell A, et al. Changes in functional imaging parameters following induction chemotherapy have important implications for individualised patient-based treatment regimens for advanced head and neck cancer. Radiother Oncol. 2013;106:112–7.PubMedCrossRef
36.
Bussink J, van Herpen CML, Kaanders JHAM, Oyen WJG. PET-CT for response assessment and treatment adaptation in head and neck cancer. Lancet Oncol. 2010;11:661–9.PubMedCrossRef
37.
Ogawa S, Lee TM, Nayak AS, Glynn P. Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Magn Reson Med. 1990;14:68–78.PubMedCrossRef
38.
Rijpkema M, Kaanders JHAM, Joosten FBM, van der Kogel AJ, Heerschap A. Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2002;53:1185–91.PubMedCrossRef
39.
McPhail LD, Robinson SP. Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. Radiology. 2010;254:110–8.PubMedCrossRef
40.
Li SP, Taylor NJ, Makris A, Ah-See M-LW, Beresford MJ, Stirling JJ, et al. Primary human breast adenocarcinoma: imaging and histologic correlates of intrinsic susceptibility-weighted MR imaging before and during chemotherapy. Radiology. 2010;257:643–52.PubMedCrossRef
41.
Dibble EH, Alvarez ACL, Truong M-T, Mercier G, Cook EF, Subramaniam RM. 18 F-FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: adding value to clinical staging. J Nucl Med. 2012;53:709–15.PubMedCrossRef
42.
Thorwarth D, Eschmann S-M, Scheiderbauer J, Paulsen F, Alber M. Kinetic analysis of dynamic 18 F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer. BMC Cancer. 2005;5:152.PubMedCentralPubMedCrossRef
43.
Schinagl DAX, Span PN, Oyen WJ, Kaanders JHAM. Can FDG PET predict radiation treatment outcome in head and neck cancer? Results of a prospective study. Eur J Nucl Med Mol Imaging. 2011;38:1449–58.PubMedCentralPubMedCrossRef
44.
Lehtiö K, Eskola O, Viljanen T, Oikonen V, Grönroos T, Sillanmäki L, et al. Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer. Radiat Oncol Biol. 2004;59:971–82.CrossRef
45.
Allal AS, Slosman DO, Kebdani T, Allaoua M, Lehmann W, Dulguerov P. Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[18 F]fluoro-2-deoxy-D-glucose. Radiat Oncol Biol. 2004;59:1295–300.CrossRef
46.
Moeller BJ, Rana V, Cannon BA, Williams MD, Sturgis EM, Ginsberg LE, et al. Prospective risk-adjusted [18 F]Fluorodeoxyglucose positron emission tomography and computed tomography assessment of radiation response in head and neck cancer. J Clin Oncol. 2009;27:2509–15.PubMedCentralPubMedCrossRef
47.
Liu W-S, Wu M-F, Tseng H-C, Liu J-T, Weng J-H, Li Y-C, et al. The role of pretreatment FDG-PET in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2012;82:561–6.PubMedCrossRef
48.
Liao C-T, Chang JT-C, Wang H-M, Ng S-H, Hsueh C, Lee L-Y, et al. Pretreatment primary tumor SUVmax measured by FDG-PET and pathologic tumor depth predict for poor outcomes in patients with oral cavity squamous cell carcinoma and pathologically positive lymph nodes. Int J Radiat Oncol Biol Phys. 2009;73:764–71.PubMedCrossRef
49.
Machtay M, Natwa M, Andrel J, Hyslop T, Anne PR, Lavarino J, et al. Pretreatment FDG-PET standardized uptake value as a prognostic factor for outcome in head and neck cancer. Head Neck. 2009;31:195–201.PubMedCrossRef
50.
Byers LA, Holsinger FC, Kies MS, William WN, El-Naggar AK, Lee JJ, et al. Serum signature of hypoxia-regulated factors is associated with progression after induction therapy in head and neck squamous cell cancer. Mol Cancer Ther. 2010;9:1755–63.PubMedCentralPubMedCrossRef
51.
Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10:472–84.PubMedCrossRef
52.
Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra24.PubMedCentralPubMedCrossRef
53.
Ritoe SC, Krabbe PFM, Kaanders JHAM, van den Hoogen FJA, Verbeek ALM, Marres HAM. Value of routine follow-up for patients cured of laryngeal carcinoma. Cancer. 2004;101:1382–9.PubMedCrossRef
54.
Boysen M, Lövdal O, Tausjö J, Winther F. The value of follow-up in patients treated for squamous cell carcinoma of the head and neck. Eur J Cancer. 1992;28:426–30.PubMedCrossRef
55.
Bhide SA, Ahmed M, Barbachano Y, Newbold K, Harrington KJ, Nutting CM. Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer. Br J Cancer. 2008;99:57–62.PubMedCentralPubMedCrossRef
56.
Bhide SA, Newbold KL, Harrington KJ, Nutting CM. Combined chemotherapy and intensity-modulated radiotherapy for the treatment of head and neck cancers. Expet Rev Anticancer Ther. 2010;10:297–300.CrossRef
57.
Wilkins AC, Rosenfelder N, Schick U, Gupta S, Thway K, Nutting CM, et al. Equivalence of cisplatin and carboplatin-based chemoradiation for locally advanced squamous cell carcinoma of the head and neck: a matched-pair analysis. Oral Oncol. 2013;49:615–9.PubMedCrossRef
58.
d’Arcy JA, Collins DJ, Padhani AR, Walker-Samuel S, Suckling J, Leach MO. Informatics in Radiology (infoRAD): Magnetic Resonance Imaging Workbench: analysis and visualization of dynamic contrast-enhanced MR imaging data. Radiographics. 2006;26:621–32.PubMedCrossRef
59.
Marcus DS, Olsen TR, Ramaratnam M, Buckner RL. The Extensible Neuroimaging Archive Toolkit: an informatics platform for managing, exploring, and sharing neuroimaging data. Neuroinformatics. 2007;5:11–34.PubMed
60.
Doran SJ, d’Arcy J, Collins DJ, Andriantsimiavona R, Orton M, Koh D-M, et al. Informatics in radiology: development of a research PACS for analysis of functional imaging data in clinical research and clinical trials. Radiographics. 2012;32:2135–50.PubMedCrossRef
61.
Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res. 1999;8:135–60.PubMedCrossRef
62.
Burton P, Gurrin L, Sly P. Extending the simple linear regression model to account for correlated responses: an introduction to generalized estimating equations and multi-level mixed modelling. Stat Med. 1998;17:1261–91.PubMedCrossRef
63.
He X, Oyadiji SO. Application of coefficient of variation in reliability-based mechanical design and manufacture. J Mater Process Tech. 2001;119:374–8.CrossRef
64.
65.
Lucs AV, Saltman B, Chung CH, Steinberg BM, Schwartz DL. Opportunities and challenges facing biomarker development for personalized head and neck cancer treatment. Head Neck. 2013;35:294–306.PubMedCentralPubMedCrossRef
66.
O’Connor JPB, Tofts PS, Miles KA, Parkes LM, Thompson G, Jackson A. Dynamic contrast-enhanced imaging techniques: CT and MRI. Br J Radiol. 2011;84(2):S112–20.PubMedCentralPubMedCrossRef
67.
Leach MO, Morgan B, Tofts PS, Buckley DL, Huang W, Horsfield MA, et al. Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging. Eur Radiol. 2012;22:1451–64.PubMedCrossRef
Metadata
Title
Prospective, longitudinal, multi-modal functional imaging for radical chemo-IMRT treatment of locally advanced head and neck cancer: the INSIGHT study
Authors
Liam Welsh
Rafal Panek
Dualta McQuaid
Alex Dunlop
Maria Schmidt
Angela Riddell
Dow-Mu Koh
Simon Doran
Iain Murray
Yong Du
Sue Chua
Vibeke Hansen
Kee H. Wong
Jamie Dean
Sarah Gulliford
Shreerang Bhide
Martin O. Leach
Christopher Nutting
Kevin Harrington
Kate Newbold
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0415-7

Other articles of this Issue 1/2015

Radiation Oncology 1/2015 Go to the issue

Research

Palliative radiotherapy with or without additional care by a multidisciplinary palliative care team in patients with newly diagnosed cancer: a retrospective matched pairs comparison

Research

French multicentre clinical evaluation of helical TomoTherapy® for anal cancer in a cohort of 64 consecutive patients

Research

Data management, documentation and analysis systems in radiation oncology: a multi-institutional survey

Research

Age most significant predictor of requiring enteral feeding in head-and-neck cancer patients

Research

Promising results with image guided intensity modulated radiotherapy for muscle invasive bladder cancer

Research

Evaluation of the optimal combinations of modulation factor and pitch for Helical TomoTherapy plans made with TomoEdge using Pareto optimal fronts