McDonald, Mark William

6006 Background: IMPT has unique biologic and physical properties compared with IMRT, limits radiation dose beyond the targeted tumor volumes, and is a novel de-intensification strategy for the management of head and neck tumors. This study was designed to compare the outcomes for patients with OPC after chemoradiation therapy (CRT) with IMRT vs IMPT. Methods: This is a multi-center, randomized, phase III non-inferiority OPC trial Stage III/IV (AJCC 7th) squamous cell carcinoma stratified patients by human papillomavirus status, smoking status, and receipt of induction chemotherapy (IC). The primary endpoint was the rate of progression-free survival (PFS) rate at 3 years, where progression was defined as disease recurrence or death. Under the null hypothesis, H0: r ≥ 1.535 established the margin for non-inferiority of IMPT. Secondary endpoints include overall survival (OS), treatment-related malnutrition, and gastrostomy-tube dependence. Analyses were conducted on intent-to-treat (ITT; n=440), per-protocol (PP; n=296), and as-treated (AT; n=397) populations. Results: Patients (n=440) were randomized to undergo IMRT(n=219) or IMPT (n=221) at 21 institutions. The median age was 61 years and HPV/p16 was positive in 95%. IC was the initial treatment in 13% of patients. All patients were treated with CRT to 70 Gy in 33 fx with bilateral neck treatment, and post-CRT surgical lymph node dissection occurred in 8%. The median follow-up was 3.14 years. In the ITT analysis, the hazard ratio (HR) for disease progression or death at 3 y was 0.87 (95%CI 0.56,1.35); p=0.006 and the corresponding HR for death (OS) was 0.63 (95%CI 0.36-1.10) suggesting a protective affect with IMPT. In PP analysis, the PFS HR was 0.85 (95%CI 0.52,1.38); p=0.009 and HR for death (OS) was 0.60 (95%CI 0.32-1.12). In the AT analysis, PFS HR was 0.88 (95%CI 0.56,1.37); p=0.007 and the corresponding HR for death (OS) was 0.70 (95%CI 0.40-1.22). For each analysis above, the null hypothesis was rejected and IMPT was non-inferior to IMRT. PP gastrostomy-tube dependence decreased with IMPT vs. IMRT from 42% to 28% (p=0.019), and more IMPT patients sustained their nutrition with end of treatment weight loss < 5% from baseline: 24% vs 14% (p=0.037). Conclusions: IMPT is non-inferior to IMRT and has emerged as a standard of care CRT approach for OPC that reduces malnutrition and gastrostomy-tube dependence. Clinical trial information: NCT01893307 .

AbstractPurposeMetallic implants have been correlated to local control failure for spinal sarcoma and chordoma patients due to the uncertainty of implant delineation from computed tomography (CT). Such uncertainty can compromise the proton Monte Carlo dose calculation (MCDC) accuracy. A component method is proposed to determine the dimension and volume of the implants from CT images.MethodsThe proposed component method leverages the knowledge of surgical implants from medical supply vendors to predefine accurate contours for each implant component, including tulips, screw bodies, lockers, and rods. A retrospective patient study was conducted to demonstrate the feasibility of the method. The reference implant materials and samples were collected from patient medical records and vendors, Medtronic and NuVasive. Additional CT images with extensive features, such as extended Hounsfield units and various reconstruction diameters, were used to quantify the uncertainty of implant contours.ResultsFor in vivo patient implant estimation, the reference and the component method differences were 0.35, 0.17, and 0.04 cm3for tulips, screw bodies, and rods, respectively. The discrepancies by a conventional threshold method were 5.46, 0.76, and 0.05 cm3, respectively. The mischaracterization of implant materials and dimensions can underdose the clinical target volume coverage by 20 cm3for a patient with eight lumbar implants. The tulip dominates the dosimetry uncertainty as it can be made from titanium or cobalt–chromium alloys by different vendors.ConclusionsA component method was developed and demonstrated using phantom and patient studies with implants. The proposed method provides more accurate implant characterization for proton MCDC and can potentially enhance the treatment quality for proton therapy. The current proof‐of‐concept study is limited to the implant characterization for lumbar spine. Future investigations could be extended to cervical spine and dental implants for head‐and‐neck patients where tight margins are required to spare organs at risk.