Multimodality functional imaging in radiation therapy during treatment: relationship between DW-MRI and 18F FDG PET in head and neck squamous cell carcinoma
David Aramburu Nuñez1,2, Antonio Lopez Medina3, Moises Mera Iglesias4, Francisco Salvador Gomez5, Vaios Hatzoglou6, Ramesh Paudyal1, Alfonso Calzado2, Joseph O Deasy1, Amita Shukla-Dave7, and Victor M Muñoz8

1Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, 2Department of Radiology, Complutense University, Madrid, Spain, 3Medical Physics & Radiological Protection, Galaria - Hospital do Meixoeiro – Complexo Hospitalario Universitario de Vigo, Vigo, Spain, 4Medical Physics, Oncoserv, Santiago de los Caballeros, Dominican Republic, 5Medical Physics and Radiological Protection, Galaria - Hospital do Meixoeiro – Complexo Hospitalario Universitario de Vigo, Vigo, Spain, 6Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, 7Medical Physics & Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, 8Radiation Oncology, Galaria - Hospital do Meixoeiro – Complexo Hospitalario Universitario de Vigo, Vigo, Spain

Synopsis

Biologically guided radiotherapy needs an understanding of how different functional imaging techniques interact and link together. DW-MRI and 18F FDG-PET techniques were used in this study for achieving this objective. 5 HPV-, HNSCC patients underwent 20 DW-MRI and 10 18F-FDG-PET/CT scans before and during radiation therapy. ADC maps derived from DW-MRI and SUV values from 18F-FDG were used for evaluating tumor response. The initial evaluation of the preliminary results suggests that in these solid tumors cellularity is inversely proportional to the glucose metabolic uptake. The survival status and functional metrics show different trends for NED, AWD and DOD.

Purpose

Human papillomavirus-negative (HPV-) head and neck cancers have poor outcome compared with HPV positive cancers1. Thus, in an effort to perform biologically guided radiotherapy it is critical to understand how different functional imaging techniques2 interact and potentially complement each other. Multimodality imaging can provide useful anatomical and functional data about tumors, including tumor cellularity measured by diffusion weighted (DW)-MRI and glucose metabolic status measured by 18F-fluorodeoxyglucose (18F-FDG) PET. In order to characterize the tumor and to implement new predictive models based on functional imaging data, we must ensure we can extract as much information as possible from the available data. Some of the main parameters to characterize tumor behavior, along with radiation therapy treatment, must be initial tumor density, hypoxia, malignancy-proliferation, dose to each voxel, and timing of the dose. In this work we focus on DW-MRI and 18F FDG-PET derived parameters. The purpose of our study was to non-invasively assess the tumor biology and metabolism of neck nodal metastases in HPV- head and neck squamous cell carcinoma (HNSCC) by investigating the relationship between tumor cellularity measured using DW-MRI and glucose metabolism measured by 18F-FDG PET.

Methods

This study was approved by local institutional review board and we obtained informed consent from all patients. Five newly diagnosed HPV- HNSCC patients with metastatic neck nodes underwent 20 DW-MRI imaging studies i.e. pre-, intra- [2 and 3 weeks] and post- chemo- radiation (dose of 70Gy) therapy. These patients also had pre- and post-and 10 18F-FDG PET/CT scans. All MRI examinations were performed on a 1.5-T scanner (Achieva; Philips Healthcare) with a Philips Sense Flex Medium coil. Standard MR images for localization and T2w Turbo Spin Echo images were obtained followed by DW-MRI acquisition using a single-shot echo planar imaging (SS-EPI) (TE/TR (ms) = 77/5270; NEX=4, FOV (cm): 23-25, slice thickness (mm)= 6 with 3 b values of b=0, 600 and 1000 s/mm², respectively. Whole-body PET/CT scan (Discovery, GE Healthcare Bio-Sciences Corp.) was performed in 3D mode from head to thigh, 60min after intravenous administration of approximately 370MBq (±10%) of 18F-FDG with a FOV(cm)= 70, matrix 218 × 218. The pixel spacing was 5.47mm with a slice thickness =3.27 mm. PET images were corrected for attenuation, scatter, decay, dead time, random coincidences and slice sensitivity. Regions of interest (ROIs) were delineated for each patient by the neuroradiologist on the primary and nodes using in-house software. The matched regions of interests from both modalities were analyzed. We registered all datasets (MRI studies, radiation dose distributions and PET/CT) in order to extract each voxel’s information (signal intensity, radiation dose and Uptake) using the software: ARTFIBio 0.6.23. To examine the correlations between DW-MRI derived apparent diffusion coefficient (ADC [mm2/s]) metric using mono-exponential fitting4 and mean of standard uptake value (SUV) measurements using established method5 from 18F-FDG PET, the non-parametric Spearman correlation coefficient was calculated. All patients had a clinical follow-up as standard of care and survival status was documented into groups at 1year: no evidence of disease [NED], alive with disease [AWD], and dead of disease [DOD].

Results

For the 5 patients, a total of 4 primary tumors and 9 nodes were analyzed. One patient had unknown primary tumor. There was a strong negative correlation between the mean of the pretreatment ADC (ρ=-0.6, p=0.008) and the 18F-FDG SUV (Figure 1). On last 1 year clinical follow up the survival status of patients was as follows: 1 NED, 2 AWD and 2 DOD. No primary was visible by MRI for delineation on the post-treatment MRI study for all patients. No node was visible by MRI for delineation on the post-treatment MRI except in the DOD patients. ADC values for pre-, 2 intra- and 1 post -treatment MRIs from primary and node of representative DOD, AWD and NED patients are shown in Table 1 (Figure 2). Figure 3 shows different trends depending on the outcome when ADC is plotted versus radiation dose.

Discussion

Multi modality imaging offers much more information about tumor biology and metabolism than the individual datasets on their own. The initial evaluation of the preliminary results suggests that in these solid tumors cellularity is inversely proportional to the glucose metabolic uptake. The survival status and functional metrics show different trends for NED, AWD and DOD.

Conclusion

These initial findings need to be validated in larger populations so that these patients can receive individualized radiation therapy.

Acknowledgements

We thank the National Health Institute of Spain for supporting this work with ISCIII Grant PI11/02035,BIOCAPS, and the Galician Government through the project CN 2012/260 “Consolidation Research Units: AtlantTIC”.

References

1. Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML, “Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial” J Natl Cancer Inst. 2008 Feb 20;100(4):261-9.

2. Jansen JF, Schöder H, Lee NY, Stambuk HE, Wang Y, Fury MG, Patel SG, Pfister DG, Shah JP, Koutcher JA, Shukla-Dave A. Tumor metabolism and perfusion in head and neck squamous cell carcinoma: pretreatment multimodality imaging with 1H magnetic resonance spectroscopy, dynamic contrast-enhanced MRI, and [18F]FDG-PET. Int J Radiat Oncol Biol Phys. 2012;82(1):299-307.

3. Landesa-Vázquez, I.., Alba-Castro, J.L, Mera-Iglesias, M., Aramburu-Núñez, D., López-Medina, and A. Muñóz-Garzón, V., "ARTFIBio: A Cross-Platform Image Registration Tool for Tumor Response Quantification in Head and Neck Cancer," in 2nd IEEE Int. Conf. on Biomedical and Health Informatics, Valencia (Spain), 2014.

4. Stejskal, E. O. and Tanner, J. E., "Spin diffusion measurements: spin echoes in the presence of a time dependent field gradient," J Chem Phys, p. 42:288–292, 1965.

5. IAEA, Quantitative Nuclear Medicine Imaging: Concepts, Requirements and Methods, IAEA Library, 2014.

Figures

Figure 1. The relationship between SUV and ADC in HPV– HNSCC patients showing an inverse correlation between the two metrics.

Figure 2. ADC map overlaid on T2W MR images. The top, middle and bottom rows are images from three HPV – HNSCC patients who were classified based on survival as DOD, AWD and NED respectively.

Figure 3. Primary tumor ADC pre- and intra- treatment (2nd and 3th week) versus radiation treatment dose in HPV – HNSCC patients who were classified based on survival as DOD, AWD and NED.

Table 1. ADC metric values for representative HPV – HNSCC patients who were classified based on survival as DOD, AWD and NED before and during therapy.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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