Shiraishi, Satomi

Abstract PURPOSE Vertebral compression fracture (VCF) is a potential adverse effect following stereotactic body radiation therapy (SBRT) for spinal metastases. In this analysis, we developed and internally validated a risk stratification model for VCF. METHODS From an initial set of 680 treatments, we excluded those with proton therapy, prior surgical intervention, or missing data. The final dataset had 464 treatments in 313 patients. Delineations of VCF and all radiographic components of the spinal instability neoplastic score (SINS) were determined by a radiologist. Recursive partitioning analysis (RPA) was conducted using separate training (70%), internal validation (15%), and test (15%) sets. The log-rank test was used as the criterion for node splitting. RESULTS With a median follow-up of 21 months, we identified 84 VCF (18%), including 65 (77%) de novo and 19 (23%) progressive fractures. There was a median 9 months (IQR: 3 – 21) to VCF. From an initial set of 15 candidate variables, six were identified using the backwards selection method, feature importance testing, and a correlation heatmap. Four were then selected in the highest-fidelity RPA models: epidural tumor extension, lumbar location, gross tumor volume > 10 cc, and SINS > 6. One point was assigned to each variable, and the resulting multivariate Cox model had a concordance of 0.760. Each one point increase in score was associated with increasing rates of VCF. Low-risk lesions (score: 0-1, n=273) had 2-year freedom from VCF of 92%, compared to 80% for intermediate-risk (score: 2, n=99) and 56% (score: 3-4, n=92) for high-risk lesions (p < 0.0001). Cumulative incidence curves with death as a competing risk showed increased VCF with higher scores via Gray’s test (p < 0.001). CONCLUSIONS Our internally-validated model identifies a subgroup of patients with high risk for VCF who may benefit from prophylactic surgical stabilization or vertebroplasty.

PURPOSE The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m 2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

PurposeThe purpose of this study was to demonstrate an objective quality control framework for the image review process.Methods and materialsA total of 927 cone‐beam computed tomography (CBCT) registrations were retrospectively analyzed for 33 bilateral head and neck cancer patients who received definitive radiotherapy. Two registration tracking volumes (RTVs) — cervical spine (C‐spine) and mandible — were defined, within which a similarity metric was calculated and used as a registration quality tracking metric over the course of treatment. First, sensitivity to large misregistrations was analyzed for normalized cross‐correlation (NCC) and mutual information (MI) in the context of statistical analysis. The distribution of metrics was obtained for displacements that varied according to a normal distribution with standard deviation of σ = 2 mm, and the detectability of displacements greater than 5 mm was investigated. Then, similarity metric control charts were created using a statistical process control (SPC) framework to objectively monitor the image registration and review process. Patient‐specific control charts were created using NCC values from the first five fractions to set a patient‐specific process capability limit. Population control charts were created using the average of the first five NCC values for all patients in the study. For each patient, the similarity metrics were calculated as a function of unidirectional translation, referred to as the effective displacement. Patient‐specific action limits corresponding to 5 mm effective displacements were defined. Furthermore, effective displacements of the ten registrations with the lowest similarity metrics were compared with a three dimensional (3DoF) couch displacement required to align the anatomical landmarks.ResultsNormalized cross‐correlation identified suboptimal registrations more effectively than MI within the framework of SPC. Deviations greater than 5 mm were detected at 2.8σ and 2.1σ from the mean for NCC and MI, respectively. Patient‐specific control charts using NCC evaluated daily variation and identified statistically significant deviations. This study also showed that subjective evaluations of the images were not always consistent. Population control charts identified a patient whose tracking metrics were significantly lower than those of other patients. The patient‐specific action limits identified registrations that warranted immediate evaluation by an expert. When effective displacements in the anterior–posterior direction were compared to 3DoF couch displacements, the agreement was ±1 mm for seven of 10 patients for both C‐spine and mandible RTVs.ConclusionsQualitative review alone of IGRT images can result in inconsistent feedback to the IGRT process. Registration tracking using NCC objectively identifies statistically significant deviations. When used in conjunction with the current image review process, this tool can assist in improving the safety and consistency of the IGRT process.