Abstract

Purpose:Patients with cancers of oropharynx have a favorable prognosis and are an ideal candidate for adaptive therapy. A replan to improve coverage or escalate/de-escalate dose based on morphological information alone may not be adequate as the grossly involved lymph nodes (LNs) of a subset of these patients tend to become cystic and often do not regress. Functional adaptation may be a better approach when considering replanning for these patients. The purpose of this study was to evaluate the weekly trends in treatment related morphological and physiological changes for these LNs using diffusion-weighted MRI (DW-MRI) and evaluate its implications for adaptive replanning.Methods:Ten patients with histologically proven oropharynx HNSCC undergoing concurrent chemoradiation were analyzed in this study. MR imaging protocol included axial T1w, T2w, and DW-MRI using a 3 T Philips MR scanner. The patients were scanned weekly in radiation treatment planning position using a 16 element phased-array anterior coil and a 44 element posterior coil. A total of 65 DWI and T2w scans were analyzed. DWI was performed using an optimized single-shot echo planar imaging sequence (TR/TE = 5000/65 ms, slice thickness = 5 mm; slices = 28; b values = 0 and 800 s/mm2). Quantification of the DW-MRI images was performed by calculating the apparent diffusion coefficient (ADC). T2w and DWI scans were imported into the Eclipse treatment planning system and gross tumor volumes (GTVs) corresponding to grossly involved LNs were contoured on each axial slice by physician experts. An attempt was made to remove any cystic or necrotic components so that the ADC analysis was of viable tumor only. A pixel-by-pixel fit of signal intensities within the GTVs was performed assuming monoexponential behavior. From each GTV histogram mean, median, standard deviation, skewness, and kurtosis were calculated. Absolute and percent change in weekly ADC histogram parameters and percent change in T2w GTV were also calculated.Results:For all nodes, an immediate change in ADC was observed during first 2–3 weeks after which ADC values either continued to increase or plateaued. A few nodal volumes had a slightly decreased ADC value during later weeks. Percent increase in median ADC from weeks 1 to 6 with respect to baseline was 14%, 25%, 41%, 42%, 45%, and 58%. The corresponding change in median T2 volumes was 8%, 10%, 16%, 22%, 40%, and 42%, respectively. The ADC distribution of the viable tumors was initially highly kurtotic; however, the kurtosis decreased as treatment progressed. The ADC distribution also showed a higher degree of skewness in the first 2 weeks, progressively becoming less skewed as treatment progressed so as to slowly approach a more symmetric distribution.Conclusions:Physiological changes in LNs represented by changes in ADC evaluated using DW-MRI are evident sooner than the morphological changes calculated from T2w MRI. The decisions for adaptive replanning may need to be individualized and should be based primarily on tumor functional information. The authors’ data also suggest that for many patients, week 3 maybe the optimal time to intervene and replan. Larger studies are needed to confirm their findings.

Highlights

  • Oropharynx squamous cell carcinoma (OSCC) associated with human papillomavirus (HPV) has a favorable prognosis

  • It is well established that HPV-positive patients are more responsive to chemotherapy and radiation therapy (RT) relative to HPV-negative patients,1 making them ideal candidates for adaptive therapy

  • The Eastern Cooperative Oncology Group (ECOG) Phase II study (E1308) that evaluated whether response to platinum-based induction chemotherapy could be used to select patients who can safely receive a lower dose of intensity modulated radiation therapy (54 instead of 74 Gy)

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Summary

Introduction

Oropharynx squamous cell carcinoma (OSCC) associated with human papillomavirus (HPV) has a favorable prognosis. It is well established that HPV-positive patients are more responsive to chemotherapy and radiation therapy (RT) relative to HPV-negative patients, making them ideal candidates for adaptive therapy. An adaptive replan to improve the coverage or escalate/de-escalate dose can be beneficial to this population in further reducing normal tissue complications. Multiple groups are looking at prospective deescalation protocols that favor deintensification of therapy. The Eastern Cooperative Oncology Group (ECOG) Phase II study (E1308) that evaluated whether response to platinum-based induction chemotherapy could be used to select patients who can safely receive a lower dose of intensity modulated radiation therapy (54 instead of 74 Gy). Two other clinical trials (NCT1088802/J0988 and NCT01221753) are exploring other radiation deintensification protocols with concomitant chemotherapy in favorable subset of HPV-associated OSCC

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