Faculty Bibliography

Purpose: Esophageal cancer patients undergoing radiotherapy usually receive daily or weekly cone-beam CT (CBCT) imaging to verify positioning before treatment. The purpose of this study is to evaluate the reproducibility of texture features extracted from CBCT and its correlation with CT features for their potential use as early predictors of esophageal cancer response during the course of RT. Methods: Ten patients treated for esophageal cancer that received daily CBCT were retrospectively evaluated (Varian TrueBeam with same Thorax imaging technique: half-fan, full-trajectory, 125 kVp, 270 mAs). The planning CT (CTP) and the two initial CBCTs (day 1 and 2 of treatment) were exported from Eclipse TPS to an in-house processing pipeline. This included edge detection for couch removal, CBCT resampling and automatic 3D rigid-registration of CBCT to CTP using Mattes mutual information metric. GTVs for each patient were exported and texture features were extracted from CTP and the registered CBCTs using the Imaging Biomarker Explorer (IBEX) software. Thirty-three texture features using cooccurrence and run-length matrices were extracted. Texture reproducibility between consecutive CBCTs was evaluated using intraclass correlation (ICC). CTP and CBCTs were evaluated using Pearson's correlation. Significance level was corrected for multiple testing using Bonferroni adjustment. Results: Registration results were deemed satisfactory using mutual information as well as visual inspection within the volume that encompassed the GTV. Out of the initial 33 texture features considered, 13 presented excellent (ICC > 0.9) reproducibility between the two initial CBCTs. Out of these 13 features, 5 presented statistically significant Pearson's correlation adjusted for multiple statistical tests (P < 0.004) ranging from 0.86 to 0.89 (Table). Conclusion: Several texture features from CBCT showed reproducibility between the first two days of treatment and strongly correlated between CTP and CBCT. Therefore, derived texture features could be investigated as predictors of treatment response during the course of treatment

Purpose or Objective Definitive chemoradiotherapy is the upfront treatment of choice in anal squamous cell carcinoma while surgery is reserved to refractory cases. Anterior peroneal resection (APR) of anal cancers often necessitates life-long a lifelong ostomy, leading to lower quality of life for the patient. High risk human papillomavirus HPV subtypes have been shown to have improved outcomes in head and neck cancer. We analyze data from a large hospital based database to evaluate the impact of high risk HPV status on APR in patients with anal cancer. Material and Methods The National Cancer Database (NC

Background: ESCC comprises 80% of esophageal cancers worldwide. Preoperative chemoRT is a standard-of-care based on the CROSS trial (N Engl J Med 2012;366:2074-2084), which reported encouraging pathologic complete response (pCR) and overall survival (OS). Surgery is often deferred in patients with clinical CR (cCR) based on lack of overall survival (OS) benefit (J Clin Oncol 2005;23:2310-2317, J Clin Oncol 2007;25:1160-1168). Nivolumab has activity in advanced ESCC (Lancet Oncol 2017;18:631-639), and adding it to chemoRT may improve outcomes. ESCC has a high somatic mutation rate and treatment with chemoRT may augment the abscopal effect.
Method(s): Our trial aims to establish the safety and tolerability (phase I), as well as the efficacy (phase II) of nivolumab added to a standard chemoRT backbone for patients with Tany N1-3 or T3-4N0 M0 ESCC. Phase I will enroll up to 12 patients and phase II, up to 44, per an optimal two-stage design. The phase I primary endpoint is unacceptable toxicity at 28 days after the last dose of chemotherapy. Phase II primary endpoints are cCR (endoscopy + PET/CT), pCR for patients undergoing surgery, and median progression-free survival and OS, which will be estimated via Kaplan Meier curves. Extensive tumor and blood immune correlative studies are planned. (Table Presented)

PURPOSE/OBJECTIVE:The purpose of this study was to assess the dosimetric equivalence of magnetic resonance (MR)-generated synthetic CT (synCT) and simulation CT for treatment planning in radiotherapy of rectal cancer. METHODS:This study was conducted on eleven patients who underwent whole-body PET/MR and PET/CT examination in a prospective IRB-approved study. For each patient synCT was generated from Dixon MR using a model-based method. Standard treatment planning directives were used to create a four-field box (4F), an oblique four-field (O4F) and a volumetric modulated arc therapy (VMAT) plan on synCT for treatment of rectal cancer. The plans were recalculated on CT with the same monitor units (MUs) as that of synCT. Dose-volume metrics of planning target volume (PTV) and organs at risk (OARs) as well as gamma analysis of dose distributions were evaluated to quantify the difference between synCT and CT plans. All plans were calculated using the analytical anisotropic algorithm (AAA). The VMAT plans on synCT and CT were also calculated using the Acuros XB algorithm for comparison with the AAA calculation. RESULTS:Medians of absolute differences in PTV metrics between synCT and CT plans were 0.2%, 0.2% and 0.3% for 4F, O4F and VMAT respectively. No significant differences were observed in OAR dose metrics including bladder V40Gy, mean dose in bladder, bowel V45Gy and femoral head V30Gy in any techniques. Gamma analysis with 2%/2mm dose difference/distance to agreement criteria showed median passing rates of 99.8% (range: 98.5 to 100%), 99.9% (97.2 to 100%), and 99.9% (99.4 to 100%) for 4F, O4F and VMAT, respectively. Using Acuros XB dose calculation, 2%/2mm gamma analysis generated a passing rate of 99.2% (97.7 to 99.9%) for VMAT plans. CONCLUSION/CONCLUSIONS:SynCT enabled dose calculation equivalent to conventional CT for treatment planning of 3D conformal treatment as well as VMAT of rectal cancer. The dosimetric agreement between synCT and CT calculated doses demonstrated the potential of MR-only treatment planning for rectal cancer using MR generated synCT.

Neoadjuvant chemoradiation has been a standard of care for locally advanced rectal cancers. Recent reports suggest that a pathologic complete response to neoadjuvant treatment correlates to improved overall survival. In addition, some series suggest that patients who have a complete response to neoadjuvant therapy may safely defer surgery in favor of a "watch and wait" approach, therefore avoiding the potential complications and adverse bowel function associated with surgery. It is therefore important to understand the clinical and biologic factors which affect the response of rectal cancers to chemoradiation. This review highlights the current literature examining the biomarkers of tumor response to chemoradiation.

Purpose: The purpose of this study is to assess the dosimetric equivalence of MR-generated synthetic CT and conventional CT for treatment planning in radiotherapy of rectal cancer. Methods: This study was conducted on eleven patients who underwent whole-body PET/MR and PET/CT examination in a prospective IRB-approved study. MR data were obtained on a 3T Siemens PET/MR hybrid scanner using a 2-point Dixon sequence. Synthetic CT (synCT) was generated from Dixon MR using a model-based method and then registered to CT using a deformable registration. Rectal tumors were artificially contoured in the synCT by a physician to define a planning tumor volume (PTV) for treatment planning comparison. Standard treatment planning directives were used to create a four-field box (4F), an oblique four-field box (O4F) and a volumetric modulated arc therapy (VMAT) plans on synCT for each PTV. The plans were recalculated on registered planCT with the same MUs as on synCT. Dose-volume metrics and gamma analysis were evaluated between synCT and CT plans. Results: Differences in PTV Dmin, D95% and Dmax between synCT and CT plans across all patients were 0.02 +/- 0.82% for 4F, -0.16 +/- 0.78% for O4F and -0.31 +/- 0.97% for VMAT plans. In any of the treatment techniques, no significant differences were observed in organs at risk (OAR) dose metrics including small bowel (V45 Gy), bladder (V40 Gy) and femoral head (V30 Gy). Gamma Analysis with 2%/2 mm dose difference/distance to agreement showed percentage pass rates of 98.7 +/- 3.1, 98.0 +/- 3.6, and 98.8 +/- 2.7 for 4F, O4F and VMAT, respectively between SynCT and CT plan. Conclusion: Planning on synCT agreed well with the dose recalculated on planning CT for conventional treatment techniques in rectal cancer radiotherapy. These results suggest the potential of MR-only radiotherapy using MR generated synCT

Purpose: Despite advances in the multimodality care in esophageal cancers, in particular the combination of chemotherapy, radiotherapy and surgery, the 5-year overall survival rate remains only 15-34%. The ability to predict treatment response is therefore of great interest, with the potential to personalize cancer treatment. This project performs a comprehensive texture feature (TF) analysis from esophageal tumor [18F]FDG PET/CT images to establish their predictive value when compared with the PET Response Criteria in Solid Tumors (PERCIST). Methods: Pre/Post chemo-radiation treatment [18F] FDG PET/CT images in sixty five patients were analyzed retrospectively. In all patients, the lesions were identified using nuclear medicine reports. The images were rigid-registered using CERR (a computational environment for clinical research), and segmented using thresholding method. Fifty features, based on the intensity histogram, second and high-order matrices, were extracted from the segmented regions from both image sets. The relative difference of SUVmax and of each TF were used as surrogates for treatment response. One-way ANOVA model of the intra-class correlation coefficient (ICC) and Spearman's rank correlation coefficient (SC) were used to establish correlations between SUVmax and TF treatment response. Results: Relative differences for fifty features were correlated with the corresponding SUVmax based on their ICC values, which were found in the range from 0.4 to 0.6. Two second-order and three high-order feature presented ICC = 0.6 (p < 0.05). Spearman's rank correlation coefficient ranged from -0.7 to 0.7. Two second-order and six high-order features presented 0.5 <= SC <= 0.6 (p < 0.05). Conclusion: Features with high ICC and SC values can be potentially used as additional metrics for treatment assessment. Hence, metabolic texture feature response provides a feasible approach for evaluating clinical outcomes in esophageal chemo-radiation