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Title: SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study

Abstract

Purpose: To prospectively evaluate the tumor vascularity assessed by perfusion CT for prediction of chemo-radiation treatment (CRT) response in locally advanced rectal cancer (LARC). Methods: Eighteen consecutive patients (61.9±8.8 years, from March–June 2015) diagnosed with LARC who underwent 6–8 weeks CRT followed by surgery were included. The pre-treatment perfusion CT was acquired after a 5s delay of contrast agent injection for 45s with 1s interval. A total of 7-cm craniocaudal range covered the tumor region with 3-mm slice thickness. The effective radiation dose is around 15mSv, which is about 1.5 the conventional abdomen/pelvis CT dose. The parametric map of blood flow (BF), blood volume (BV), mean transit time (MTT), permeability (PMB), and maximum intensity map (MIP) were obtained from commercial software (Syngo-CT 2011A, Siemens). An experienced radiation oncologist outlined the tumor based on the pre-operative MR and pathologic residual region, but was blinded with regards to pathological tumor stage. The perfusion parameters were compared to histopathological response quantified by tumor regression grade as good-responder (GR, TRG 0-1) vs. non-good responder (non-GR). Furthermore, the predictive value for pathological complete response (pCR) was also investigated. Results: Both BV (p=0.02) and MTT (P=0.02) was significantly higher and permeambility was lower (p=0.004) in themore » good responders. The BF was higher in GR group but not statistically significant. Regarding the discrimination of pCR vs non-pCR, the BF was higher in the pCR group (p=0.08) but none of those parameters showed statistically significant differences. Conclusion: BV and MTT can discriminate patients with a favorable response from those that fail to respond well, potentially selecting high-risk patients with resistant tumors that may benefit from an aggressive preoperative treatment approach. However, future studies with more patient data are needed to verify the prognostic value of perfusion CT especially for pCR prediction. This work is supported by the National High-tech R&D program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917), Natural Science Foundation of China (NSFC Grant No. 81201091).« less

Authors:
; ; ;  [1]; ; ; ; ; ;  [2]
  1. Rutgers-Cancer Institute of New Jersey, Rutgers-Robert Wood Johnson Medical, New Brunswick, NJ (United States)
  2. Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang (China)
Publication Date:
OSTI Identifier:
22626767
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ABDOMEN; BLOOD; BLOOD FLOW; COMPUTER CODES; COMPUTERIZED TOMOGRAPHY; CONTRAST MEDIA; DIAGNOSIS; HAZARDS; INJECTION; MEDICAL PERSONNEL; NEOPLASMS; PATIENTS; PELVIS; PERMEABILITY; POLYMERASE CHAIN REACTION; RADIATION DOSES; RADIOTHERAPY; RECTUM; SURGERY; THICKNESS

Citation Formats

Nie, K, Yue, N, Jabbour, S, Kim, S, Shi, L, Mao, T, Qian, L, Hu, X, Sun, X, and Niu, T. SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study. United States: N. p., 2016. Web. doi:10.1118/1.4955819.
Nie, K, Yue, N, Jabbour, S, Kim, S, Shi, L, Mao, T, Qian, L, Hu, X, Sun, X, & Niu, T. SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study. United States. doi:10.1118/1.4955819.
Nie, K, Yue, N, Jabbour, S, Kim, S, Shi, L, Mao, T, Qian, L, Hu, X, Sun, X, and Niu, T. 2016. "SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study". United States. doi:10.1118/1.4955819.
@article{osti_22626767,
title = {SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study},
author = {Nie, K and Yue, N and Jabbour, S and Kim, S and Shi, L and Mao, T and Qian, L and Hu, X and Sun, X and Niu, T},
abstractNote = {Purpose: To prospectively evaluate the tumor vascularity assessed by perfusion CT for prediction of chemo-radiation treatment (CRT) response in locally advanced rectal cancer (LARC). Methods: Eighteen consecutive patients (61.9±8.8 years, from March–June 2015) diagnosed with LARC who underwent 6–8 weeks CRT followed by surgery were included. The pre-treatment perfusion CT was acquired after a 5s delay of contrast agent injection for 45s with 1s interval. A total of 7-cm craniocaudal range covered the tumor region with 3-mm slice thickness. The effective radiation dose is around 15mSv, which is about 1.5 the conventional abdomen/pelvis CT dose. The parametric map of blood flow (BF), blood volume (BV), mean transit time (MTT), permeability (PMB), and maximum intensity map (MIP) were obtained from commercial software (Syngo-CT 2011A, Siemens). An experienced radiation oncologist outlined the tumor based on the pre-operative MR and pathologic residual region, but was blinded with regards to pathological tumor stage. The perfusion parameters were compared to histopathological response quantified by tumor regression grade as good-responder (GR, TRG 0-1) vs. non-good responder (non-GR). Furthermore, the predictive value for pathological complete response (pCR) was also investigated. Results: Both BV (p=0.02) and MTT (P=0.02) was significantly higher and permeambility was lower (p=0.004) in the good responders. The BF was higher in GR group but not statistically significant. Regarding the discrimination of pCR vs non-pCR, the BF was higher in the pCR group (p=0.08) but none of those parameters showed statistically significant differences. Conclusion: BV and MTT can discriminate patients with a favorable response from those that fail to respond well, potentially selecting high-risk patients with resistant tumors that may benefit from an aggressive preoperative treatment approach. However, future studies with more patient data are needed to verify the prognostic value of perfusion CT especially for pCR prediction. This work is supported by the National High-tech R&D program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917), Natural Science Foundation of China (NSFC Grant No. 81201091).},
doi = {10.1118/1.4955819},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose: Accurate delineation of target volumes is important to maximize radiation dose to the tumor and minimize it to nontumor tissue. Computed tomography (CT) and magnetic resonance imaging (MRI) are standard imaging modalities in rectal cancer. The aim was to explore whether functional imaging with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), combined with CT (FDG-PET/CT) gives additional information to standard pretreatment evaluation and changes the shape and size of the gross tumor volume (GTV). Methods and Materials: From 2007 to 2009, 77 consecutive patients with locally advanced rectal cancer were prospectively screened for inclusion in the study at twomore » university hospitals in Sweden, and 68 patients were eligible. Standard GTV was delineated using information from clinical examination, CT, and MRI (GTV-MRI). Thereafter, a GTV-PET was defined in the fused PET-CT, and the target volume delineations were compared for total volume, overlap, and mismatch. Pathologic uptake suspect of metastases was also registered. Results: The median volume of GTV-MRI was larger than that of GTV-PET: 111 cm{sup 3} vs. 87 cm{sup 3} (p < 0.001). In many cases, the GTV-MRI contained the GTV defined on the PET/CT images as subvolumes, but when a GTV total was calculated after the addition of GTV-PET to GTV-MRI, the volume increased, with median 11% (range, 0.5-72%). New lesions were seen in 15% of the patients for whom PET/CT was used. Conclusions: FDG-PET/CT facilitates and adds important information to the standard delineation procedure of locally advanced rectal cancer, mostly resulting in a smaller GTV, but a larger total GTV using the union of GTV-MRI and GTV-PET. New lesions were sometimes seen, potentially changing the treatment strategy.« less
  • Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific 'signature' correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy. Methods and Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsiesmore » obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study. Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909 Asterisk-Operator , miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.« less
  • Purpose: We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting. Methods and Materials: Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80mg/m{sup 2} on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80mg/m{sup 2}) was infused on Days 1, 8, 22, and 29. Four or more weeksmore » after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety. Results: We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea. Conclusions: A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.« less
  • Purpose: Morphologic imaging techniques perform poorly in assessing the response to preoperative radiotherapy (RT), mainly because of desmoplastic reactions. The aim of this study was to investigate the potential of sequential 18-fluoro-2-deoxy-D-glucose (18FDG-PET) in assessing the response of rectal cancer to neoadjuvant RT and to determine which parameters can be used as surrogate markers for histopathologic response. Methods and Materials: 18FDG-PET scans were acquired before and during the 5th week after the end of RT. Tracer uptake was assessed semiquantitatively using standardized uptake values (SUV). The percentage differences (%{Delta}) between pre- and post-RT scans in SUV{sub max}, SUV{sub mean}, metabolicmore » volume (MV), and total glycolytic volume (tGV) were calculated. Results: Forty-five consecutive patients with histologically confirmed rectal adenocarcinoma were enrolled. After neoadjuvant RT, 20 of the 45 patients were classified as histopathologic responders and 25 as non-responders. Intense 18F-FDG uptake was seen in all tumors before neoadjuvant RT (average SUV{sub max} 12.9 {+-} 6.0). When patients were classified as histologic responders and nonresponders, significant differences in %{Delta}SUV{sub max} (55.8% vs. 37.4%, p = 0.023) and %{Delta}SUV{sub mean} (40.1% vs. 21.0%, p = 0.001) were observed between the two groups. For %{Delta}MV and %{Delta}tGV, decreases were more prominent in responders but were not significantly different from those in nonresponders. As demonstrated by receiver operating characteristic analysis, %{Delta}SUV{sub mean} was a more powerful discriminator than was %{Delta}SUV{sub max}. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for optimal threshold of %{Delta}SUV{sub mean} (24.5%) were 80%, 72%, 76%, 70%, and 82% respectively. Conclusion: Sequential 18FDG-PET allows assessment of the response to preoperative RT. Both %{Delta}SUV{sub mean} and %{Delta}SUV{sub max} correlate with histopathologic response and can be used to evaluate and compare the effectiveness of different neoadjuvant treatment strategies. The maximum accuracy figures and the positive predictive value figures for both {Delta}%SUV{sub mean} and {Delta}%SUV{sub max} are, however, too low to justify modification of the standard treatment protocol of an individual patient.« less
  • Purpose: To compare three different pharmacokinetic models for analysis of dynamic-contrast-enhanced (DCE)-CT data with respect to different acquisition times and location of region of interest. Methods: Eight rectal cancer patients with pre-treatment DCE-CTs were included. The dynamic sequence started 4–10seconds(s) after the injection of contrast agent. The scan included a 110s acquisition with intervals of 40×1s+15×3s+4×6s. An experienced oncologist outlined the tumor region. Hotspots with top-5%-enhancement were also identified. Pharmacokinetic analysis was performed using three different models: deconvolution method, Patlak model, and modified Toft’s model. Perfusion parameters as blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface-area-product (PS),more » volume transfer constant (Ktrans), and flux rate constant (Kep), were compared with respect to different acquisition times of 45s, 65s, 85s and 105s. Both hotspot and whole-volume variances were also assessed. The differences were compared using the Wilcoxon matched-pairs test and Bland-Altman plots. Results: Moderate correlation was observed for various perfusion parameters (r=0.56–0.72, p<0.0001) but the Wilcoxon test revealed a significant difference among the three models (P < .001). Significant differences in PS were noted between acquisitions of 45s versus longer time of 85s or 105s (p<0.05) using Patlak but not with the deconvolution method. In addition, measurements varied substantially between whole-volume vs. hotspot analysis. Conclusion: The radiation dose of DCE-CT was on average 1.5 times of an abdomen/pelvic CT, which is not insubstantial. To take the DCE-CT forward as a biomarker in oncology, prospective studies should be carefully designed with the optimal image acquisition and analysis technique. Our study suggested that: (1) different kinetic models are not interchangeable; (2) a 45s acquisition might not be sufficient for reliable permeability measurement in rectal cancer using Patlak model, but might be achievable using deconvolution method; and (3) local variations existed inside the tumor, and both whole-volume-averaged and local-heterogeneity analysis is recommended for future quantitative studies. This work is supported by the National High-tech R&D program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917), Natural Science Foundation of China (NSFC Grant No. 81201091).« less