B Cannon

Prospective Risk-Adjusted [18F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography Assessment of Radiation Response in Head and Neck Cancer

PURPOSE [(18)F]Fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) imaging may improve assessment of radiation response in patients with head and neck cancer, but it is not yet known for which patients this is most useful. We conducted a prospective trial to identify patient populations likely to benefit from the addition of functional imaging to the assessment of radiotherapy response. PATIENTS AND METHODS Ninety-eight patients with locally advanced cancer of the oropharynx, larynx, or hypopharynx were prospectively enrolled and treated with primary radiotherapy, with or without chemotherapy. Patients underwent FDG-PET/CT and contrast-enhanced CT imaging 8 weeks after completion of treatment. Functional and anatomic imaging response was correlated with clinical and pathologic response. Imaging accuracy was then compared between imaging modalities. RESULTS Although postradiation maximum standard uptake values were significantly higher in nonresponders compared with responders, the positive and negative predictive values of FDG-PET/CT scanning were similar to those for CT alone in the unselected study population. Subset analyses revealed that FDG-PET/CT outperformed CT alone in response assessment for patients at high risk for treatment failure (those with human papillomavirus [HPV] -negative disease, nonoropharyngeal primaries, or history of tobacco use). No benefit to FDG-PET/CT was seen for low-risk patients lacking these features. CONCLUSION These data do not support the broad application of FDG-PET/CT for radiation response assessment in unselected head and neck cancer patients. However, FDG-PET/CT may be the imaging modality of choice for patients with highest risk disease, particularly those with HPV-negative tumors. Optimal timing of FDG-PET/CT imaging after radiotherapy merits further investigation.

Prospective Imaging Assessment of Mortality Risk After Head-and-Neck Radiotherapy

PURPOSE The optimal roles for imaging-based biomarkers in the management of head-and-neck cancer remain undefined. Unresolved questions include whether functional or anatomic imaging might improve mortality risk assessment for this disease. We addressed these issues in a prospective institutional trial. METHODS AND MATERIALS Ninety-eight patients with locally advanced pharyngolaryngeal squamous cell cancer were enrolled. Each underwent pre- and post-chemoradiotherapy contrast-enhanced computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT imaging. Imaging parameters were correlated with survival outcomes. RESULTS Low post-radiation primary tumor FDG avidity correlated with improved survival on multivariate analysis; so too did complete primary tumor response by CT alone. Although both imaging modalities lacked sensitivity, each had high specificity and negative predictive value for disease-specific mortality risk assessment. Kaplan-Meier estimates confirmed that both CT and FDG-PET/CT stratify patients into distinct high- and low-probability survivorship groups on the basis of primary tumor response to radiotherapy. Subset analyses demonstrated that the prognostic value for each imaging modality was primarily derived from patients at high risk for local treatment failure (human papillomavirus [HPV]-negative disease, nonoropharyngeal primary disease, or tobacco use). CONCLUSIONS CT alone and FDG-PET/CT are potentially useful tools in head-and-neck cancer-specific mortality risk assessment after radiotherapy, particularly for selective use in cases of high-risk HPV-unrelated disease. Focus should be placed on corroboration and refinement of patient selection for imaging-based biomarkers in future studies.

Metabolic Imaging Biomarkers of Postradiotherapy Xerostomia

PURPOSE Xerostomia is a major complication of head and neck radiotherapy (RT). Available xerostomia measures remain flawed. [(18)F]fluorodeoxyglucose-labeled positron emission tomography-computed tomography (FDG-PET-CT) is routinely used for staging and response assessment of head and neck cancer. We investigated quantitative measurement of parotid gland FDG uptake as a potential biomarker for post-RT xerostomia. METHODS AND MATERIALS Ninety-eight locally advanced head and neck cancer patients receiving definitive RT underwent baseline and post-RT FDG-PET-CT on a prospective imaging trial. A separate validation cohort of 14 patients underwent identical imaging while prospectively enrolled in a second trial collecting sialometry and patient-reported outcomes. Radiation dose and pre- and post-RT standard uptake values (SUVs) for all voxels contained within parotid gland ROI were deformably registered. RESULTS Average whole-gland or voxel-by-voxel models incorporating parotid D(Met) (defined as the pretreatment parotid SUV weighted by dose) accurately predicted posttreatment changes in parotid FDG uptake (e.g., fractional parotid SUV). Fractional loss of parotid FDG uptake closely paralleled early parotid toxicity defined by posttreatment salivary output (p < 0.01) and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia scores (p < 0.01). CONCLUSIONS In this pilot series, loss of parotid FDG uptake was strongly associated with acute clinical post-RT parotid toxicity. D(Met) may potentially be used to guide function-sparing treatment planning. Prospective validation of FDG-PET-CT as a convenient, quantifiable imaging biomarker of parotid function is warranted and ongoing.

SU‐GG‐J‐146: Evaluation of Parotid Density Changes during IMRT of Head‐And‐Neck Cancer

Purpose: To evaluate the change in parotid gland density over the course of treatment for patients who have undergone adaptive radiation therapy to the head‐and‐neck. Method and Materials:Computed tomography(CT)images from sixteen patients were analyzed to assess the change in mean parotid density and parotid volume over the course of treatment. Daily CTimages were acquired for a group of patients treated with adaptive radiation therapy using a CT‐on‐rails unit. A total of 529 CT scans (∼33 fractions per patient) were analyzed. Parotid contours were deformed from the planning CT to each treatment day CTimage using an in‐house deformable image registration tool. The parotid volume, and average and standard deviation in CT number (HU) were obtained for each treatment fraction. Linear regression analysis was performed with a 95% confidence interval to determine the rate and trend of parotid density change. The Pearson correlation coefficient was used to evaluate possible correlations with parotid volume and function measurements. Results: Eleven of the sixteen patients showed a steady decrease in density for both parotids over the course of treatment. Two patients showed a steady decrease only in their ipsilateral parotid. The linear regression analysis for this subset of patients (p‐value <0.01) revealed an average rate of decrease of 0.30 HU/fraction (range 0.13–0.70 HU/fraction). The density reduction correlated well with parotid volume change (in 24/32 instances), and was moderately correlated with patient follow‐up saliva‐flow measurements (9 patients, correlation coefficient range 0.27–0.63) for the first two follow‐up appointments. Conclusion: The mean parotid density decreased steadily and correlated well with the volume shrinkage in most patients observed in this study. In the limited available data, the density change also correlated with saliva‐flow, which warrants future studies with a larger patient population and additional treatment parameters.

SU‐GG‐J‐153: Voxel‐Based Phenomenological SUV‐Dose Response Model for the Human Parotid Glands

Purpose: The goal of this study is to evaluate SUV as an imaging biomarker of parotid function following radiotherapy (RT) and to develop a phenomenological model of SUV‐dose response, enabling prediction of the biomarker prior to RT. Method and Materials: As part of an ongoing study, patients (n = 8) with head and neck cancer (HNC) had 18F‐FDG PET/CT studies performed before (within 30 days) and following RT (∼50 days). In addition, resting and stimulated whole mouth saliva was collected. Next, a deformable image registration algorithm was utilized to map parotid contours from planning CT (PCT) images to pre‐ and post‐RT PET/CT studies, separately. Mean SUV was then calculated for the parotid glands at both time points and compared to collected saliva. The SUV‐dose response relationship was assessed in a separate cohort (n = 60) also treated for HNC. Pre‐ and post‐RT PET/CT images were deformably aligned to PCT images to achieve correspondence between SUV and planned dose. SUV response was then modeled using a single parameter, incorporating planned dose and pre‐RT SUV; defined as metabolic dose.Results: Post‐RT stimulated saliva and SUV decreased (59% and 20%, respectively) in seven patients. For one patient, stimulated saliva and SUV increased (14% and 11%, respectively). Fractional SUV correlated significantly with xerostomia grade, P < 0.01 and Spearmans ρ = −0.964. A second order polynomial provided an adequate fit to the log transformed SUV‐dose response curve, adjusted R2 = 0.95. Post‐RT SUV was predicted within 3% for an exemplary patient, but overestimated (50%) in the worst case. Conclusions: Pilot data suggest that SUV is significantly correlated with parotid saliva output. Furthermore, the feasibility of predicting reductions in SUV, prior to treatment delivery, has been demonstrated. Conflict of Interest: Research partially sponsored by Varian Medical Systems.

SU‐FF‐J‐131: Improving Quantitation in Serial PET/CT with Improved Image Registration and Intra‐Patient Metabolic Correction

Purpose: The goal of this study is to explore the use of deformable image registration in conjunction with an internal metabolic reference to improve quantitative treatment response assessment using F18‐FDG PET/CT. Method and Materials: To account for anatomic and positional changes, pre‐ and post‐radiotherapy (RT) PET/CT studies were aligned with a deformable image registration technique to the planning CT (PCT). Consequently, both CT‐ and PET‐based regions‐of‐interest on all co‐registered image sets can be used to determine uptake for the same anatomic volumes. The brainstem, contoured on PCT, was selected as an internal metabolic normalization structure to correct for study dependent variations; particularly, inconsistent injection‐to‐imaging time. The mean SUV was calculated using a threshold contour (40% of maximum) method, created on the pre‐RT PET/CT images. Students t‐tests and receiver operating characteristic (ROC) analyses were performed for metabolically corrected (uptake ratio of tumor to brainstem) and uncorrected mean and maximum SUV. Results: A statistically detectable separation was improved between responding and non‐responding patients using the corrected post‐RT mean SUV for the threshold contour (P=0.017 vs. P=0.00); while no worsening was seen for the maximum SUV (P<0.00 vs. P<0.00). Reduction of uptake the between pre‐ and post‐RT images was only significant for the maximum SUV (P=0.033) and subsequently improved when corrected with the metabolic reference (P=0.012). Finally, ROC analysis of the maximum corrected post‐RT SUV showed improvement in specificity (94% vs. 85%) and similar results for the sensitivity (83% vs. 83%) level. However, ROC analyses of corrected and uncorrected mean post‐RT SUV derived from the threshold contour did not show improvement. Conclusions: Multiple lines of evidence demonstrate that correction of SUV with an internal metabolic reference may improve the quantitative potential of F18‐FDG PET/CT. Conflict of Interest: Research sponsored by Varian Medical Systems.

SU‐GG‐J‐163: Radiotherapy Response Assessment Using Deformed Serial 18F‐FDG PET/CT

Purpose: To assess the ability of SUV measured on serial 18 F ‐ FDG PET/CT to differentiate radiotherapy (RT) responders from non‐responders. Method and Materials: Between November 2005 and August 2007, 88 eligible patients with AJCC stage III‐IVb HNSCC were enrolled in an IRB approved protocol to receive serial PET/CT imaging studies prior to and following RT. Analysis of similar anatomic volumes on temporally separated images was facilitated with a deformable image registration technique to map pre‐ and post‐RT CTimages to a reference image set, namely the RT planning CTimages. The resulting deformable transformations were applied to the pre‐ and post‐RT PETimages, thereby aligning both PETdata sets to the RT planning CTimages. SUV reduction factors were created from pre‐ and post‐RT SUV ratios and calculated for RT contours and fixed thresholds of the maximum signal intensity on PETimages. Variations in pre‐ and post‐RT PET/CT scannermodel and uptake duration were controlled to eliminate possible confounding factors for intrapatient analysis.Results: Cross correlation of patients whose serial PET/CT images were collected with the same scannermodel and with uptake duration differences ⩽ 15 min reduced the useable number of patients drastically from 88 to 10. For the controlled patient cohort, the average SUV reduction factor for responders (N = 7) vs. non‐responders (N = 3) calculated for the GTV contour was (1.4 ± 1.6) and (1.0 ± 1.7), respectively. For all contours (N = 4), nonparametric testing revealed [P > 0.05]. Conclusion: The average SUV reduction factor was not able to significantly differentiate responders and non‐responders in all contours studied. The large reduction in useable patients following strict data set control may be an important cautionary note for future studies investigating serial PET/CT for treatment response monitoring. Research sponsored by Varian Medical Systems.

SU‐EE‐A3‐04: ROI‐Based Response Assessment Using Pre‐ and Post‐RT 18F‐FDG PET/CT

Purpose: To assess the therapy‐induced changes of head and neck cancers using 18F‐FDG PET/CT imaging studies performed prior to and following the completion of a course of radiotherapy (RT) through a region‐of‐interest based (ROI) analysis.Method and Materials: As part of an ongoing study, nine patients with carcinoma of the head and neck had PET/CT imaging studies performed prior to the start of treatment (range: 4 – 58 days; median: 36 days) and following the conclusion of treatment (range: 33 – 63 days; median: 59 days). RT contours, created with the Pinnacle treatment planning system and CT simulation images, from physician‐approved plans were collected to align with pre‐ and post‐RT PET/CT images. Utilizing in‐house developed software, the contours were deformed to the pre‐ and post‐RT PET/CT images through a non‐rigid registration. The non‐rigidly aligned RT contours were then used as ROIs to collect data from the pre‐and post‐RT PET images. The standard uptake value (SUV) was calculated assuming that identical structures were contained in the pre‐ and post‐RT deformed volumes, which were altered by anatomic changes as a result of RT. Results: For the GTV contour, the mean pre‐ and post‐RT SUV and standard deviation was (5.6 ± 0.9) and (2.4 ± 0.6), respectively. Within the GTV, the mean maximum SUV prior to RT was (23 ± 4.6), while after the conclusion of RT, the mean maximum SUV was (5.0 ± 1.9). Additionally, the mean ratio of the pre‐ to post‐RT mean SUV was (2.5 ± 0.7), indicating an overall decrease in uptake of the tracer in tissues within the GTV contour. Conclusion: Through the use of deformable image registration, the feasibility of 18F‐FDG PET/CT ROI‐based analyses of RT‐induced changes in patients with head and neck cancers has been demonstrated.