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Title: A comparative study of volumetric analysis, histopathologic downstaging, and tumor regression grade in evaluating tumor response in locally advanced rectal cancer following preoperative chemoradiation

Abstract

Purpose: To compare tumor volume reduction rate, histopathologic downstaging, and tumor regression grade (TRG) among tumor responses in rectal cancer after preoperative chemoradiotherapy (CRT). Patients and Methods: Between 2002 and 2004, 30 patients with locally advanced rectal cancer underwent preoperative CRT, followed by surgical resection. Magnetic resonance volumetry was performed before and after CRT. Histopathologic tumor staging and tumor regression were reviewed. We compared pre- and post-CRT tumor volume and percent of volume reduction, according to histopathologic downstaging and TRG. Results: The tumor volume reduction rates ranged from 14.6% to 100%. Mean pre- and post-CRT tumor volumes were significantly smaller in patients who showed T downstaging than in those who did not (p 0.040, 0.014). The mean tumor volume reduction was 66.4% vs. 55.2% (p 0.361). However, the mean pre- and post-CRT tumor volume and mean tumor volume reduction rate between patients who showed N downstaging and those who did not were not statistically different (p = 0.176, 0.767, and 0.899). With respect to TRG, the mean pre- and post-CRT tumor volumes were not statistically significant (p = 0.108, 0.708, and 0.120). Conclusion: Tumor volume reduction rate does not correlate with histopathologic downstaging and TRG. It might be hazardous tomore » evaluate tumor response with respect to volume reduction and to select the surgical method on this basis.« less

Authors:
 [1];  [2];  [3];  [2];  [3];  [4];  [5];  [2];  [3];  [2];  [3];  [2];  [3];  [6];  [6]
  1. Colorectal Cancer Clinic Severance Hospital, Yonsei University Medical Center, Seoul (Korea, Republic of) and Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of). E-mail: namkyuk@yumc.yonsei.ac.kr
  2. Colorectal Cancer Clinic Severance Hospital, Yonsei University Medical Center, Seoul (Korea, Republic of)
  3. (Korea, Republic of)
  4. National Cancer Center, Proton Therapy Center, Ilsan (Korea, Republic of)
  5. Department of Pathology, National Insurance Hospital, Ilsan (Korea, Republic of)
  6. Department of Medical Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)
Publication Date:
OSTI Identifier:
20850315
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.08.020; PII: S0360-3016(06)02769-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; COMBINED THERAPY; NEOPLASMS; PATHOLOGICAL CHANGES; PATIENTS; SURGERY; VOLUMETRIC ANALYSIS

Citation Formats

Kim, Nam Kyu, Baik, Seung Hyuk, Department of Surgery, Yonsei University College of Medicine, Seoul, Min, Byung Soh, Department of Surgery, Yonsei University College of Medicine, Seoul, Pyo, Hong Ryull, Choi, Yun Jung, Kim, Hogeun, Department of Pathology, Yonsei University College of Medicine, Seoul, Seong, Jinsil, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Keum, Ki Chang, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Rha, Sun Young, and Chung, Hyun Cheol. A comparative study of volumetric analysis, histopathologic downstaging, and tumor regression grade in evaluating tumor response in locally advanced rectal cancer following preoperative chemoradiation. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.08.020.
Kim, Nam Kyu, Baik, Seung Hyuk, Department of Surgery, Yonsei University College of Medicine, Seoul, Min, Byung Soh, Department of Surgery, Yonsei University College of Medicine, Seoul, Pyo, Hong Ryull, Choi, Yun Jung, Kim, Hogeun, Department of Pathology, Yonsei University College of Medicine, Seoul, Seong, Jinsil, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Keum, Ki Chang, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Rha, Sun Young, & Chung, Hyun Cheol. A comparative study of volumetric analysis, histopathologic downstaging, and tumor regression grade in evaluating tumor response in locally advanced rectal cancer following preoperative chemoradiation. United States. doi:10.1016/j.ijrobp.2006.08.020.
Kim, Nam Kyu, Baik, Seung Hyuk, Department of Surgery, Yonsei University College of Medicine, Seoul, Min, Byung Soh, Department of Surgery, Yonsei University College of Medicine, Seoul, Pyo, Hong Ryull, Choi, Yun Jung, Kim, Hogeun, Department of Pathology, Yonsei University College of Medicine, Seoul, Seong, Jinsil, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Keum, Ki Chang, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Rha, Sun Young, and Chung, Hyun Cheol. Mon . "A comparative study of volumetric analysis, histopathologic downstaging, and tumor regression grade in evaluating tumor response in locally advanced rectal cancer following preoperative chemoradiation". United States. doi:10.1016/j.ijrobp.2006.08.020.
@article{osti_20850315,
title = {A comparative study of volumetric analysis, histopathologic downstaging, and tumor regression grade in evaluating tumor response in locally advanced rectal cancer following preoperative chemoradiation},
author = {Kim, Nam Kyu and Baik, Seung Hyuk and Department of Surgery, Yonsei University College of Medicine, Seoul and Min, Byung Soh and Department of Surgery, Yonsei University College of Medicine, Seoul and Pyo, Hong Ryull and Choi, Yun Jung and Kim, Hogeun and Department of Pathology, Yonsei University College of Medicine, Seoul and Seong, Jinsil and Department of Radiation Oncology, Yonsei University College of Medicine, Seoul and Keum, Ki Chang and Department of Radiation Oncology, Yonsei University College of Medicine, Seoul and Rha, Sun Young and Chung, Hyun Cheol},
abstractNote = {Purpose: To compare tumor volume reduction rate, histopathologic downstaging, and tumor regression grade (TRG) among tumor responses in rectal cancer after preoperative chemoradiotherapy (CRT). Patients and Methods: Between 2002 and 2004, 30 patients with locally advanced rectal cancer underwent preoperative CRT, followed by surgical resection. Magnetic resonance volumetry was performed before and after CRT. Histopathologic tumor staging and tumor regression were reviewed. We compared pre- and post-CRT tumor volume and percent of volume reduction, according to histopathologic downstaging and TRG. Results: The tumor volume reduction rates ranged from 14.6% to 100%. Mean pre- and post-CRT tumor volumes were significantly smaller in patients who showed T downstaging than in those who did not (p 0.040, 0.014). The mean tumor volume reduction was 66.4% vs. 55.2% (p 0.361). However, the mean pre- and post-CRT tumor volume and mean tumor volume reduction rate between patients who showed N downstaging and those who did not were not statistically different (p = 0.176, 0.767, and 0.899). With respect to TRG, the mean pre- and post-CRT tumor volumes were not statistically significant (p = 0.108, 0.708, and 0.120). Conclusion: Tumor volume reduction rate does not correlate with histopathologic downstaging and TRG. It might be hazardous to evaluate tumor response with respect to volume reduction and to select the surgical method on this basis.},
doi = {10.1016/j.ijrobp.2006.08.020},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 67,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
  • Background and Purpose: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Methods and Materials: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m{sup 2}/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Results: Fifty patients completed preoperative treatment according to themore » protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Conclusions: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.« less
  • Purpose: To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods and Materials: A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging wasmore » defined as a reduction of at least one T-stage level. Results: Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p 0.012 vs. odds ratio, 3.235; p < 0.001, respectively). Conclusion: A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer.« less
  • Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from themore » histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.« less
  • Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{supmore » 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.« less
  • Purpose: Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen. Methods and Materials: Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40more » mg/m{sup 2} of irinotecan per week for 5 consecutive weeks and 1,650 mg/m{sup 2} of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints. Results: In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32-72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2-37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death. Conclusions: Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.« less