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Title: Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer

Abstract

Purpose: Postoperative chemoradiotherapy in gastric cancer improves locoregional control and survival. Reports on late toxicity, however, have been scarce thus far. Because renal toxicity is one of the most serious late complications in upper abdominal radiotherapy, we prospectively analyzed kidney function in patients who underwent postoperative chemoradiotherapy for gastric cancer. Patients and Methods: In 44 patients, Tc{sup 99m}-thiatide renography was performed before and at regular intervals after postoperative chemoradiotherapy. The left-to-right (L/R) ratio was used as an index of the relative kidney function. Mean L/R values were calculated for four follow-up time intervals. For all patients, kidney V{sub 20} (percentage of the volume of the kidney that received more than 20 Gy) and mean dose of both kidneys were retrieved from the three-dimensional dose-volume histograms. Results: We observed a progressive decrease in left renal function of 11% (p = 0.012) after 6 months, up to 52% (p < 0.001) after >18 months. The V{sub 20} (left kidney) and mean left kidney dose were identified as parameters associated with decreased kidney function. Mean serum creatinine was increased from 74.6 {mu}mol/L before treatment to 86.1 {mu}mol/L at 1 year after chemoradiotherapy (p < 0.001). In patients with a follow-up of 18-28 months,more » one case of severe renovascular hypertension was observed. Conclusion: A progressive relative functional impairment of the left kidney in patients after postoperative chemoradiotherapy for gastric cancer is demonstrated. To optimize the survival benefit that can be established with adjuvant regimens, strategies to minimize the dose to the kidneys and other critical organs should be explored.« less

Authors:
 [1];  [2];  [3];  [4];  [4];  [2];  [3];  [4];  [5];  [4];  [4]
  1. Department of Radiotherapy, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands). E-mail: epm.jansen@nki.nl
  2. Department of Radiation Oncology, Christie Hospital NHS Trust, Manchester (United Kingdom)
  3. Department of Gastroenterology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
  4. Department of Radiotherapy, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
  5. Department of Nuclear Medicine, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
Publication Date:
OSTI Identifier:
20944729
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2006.09.012; PII: S0360-3016(06)02991-9; 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; CARCINOMAS; COMBINED THERAPY; CREATININE; CRITICAL ORGANS; HYPERTENSION; KIDNEYS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; RENOGRAPHY; TECHNETIUM 99; TOXICITY

Citation Formats

Jansen, Edwin, Saunders, Mark P., Boot, Henk, Oppedijk, Vera, Dubbelman, Ria, Porritt, Bridget, Cats, Annemieke, Stroom, Joep, Valdes Olmos, Renato, Bartelink, Harry, and Verheij, Marcel. Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.09.012.
Jansen, Edwin, Saunders, Mark P., Boot, Henk, Oppedijk, Vera, Dubbelman, Ria, Porritt, Bridget, Cats, Annemieke, Stroom, Joep, Valdes Olmos, Renato, Bartelink, Harry, & Verheij, Marcel. Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer. United States. doi:10.1016/j.ijrobp.2006.09.012.
Jansen, Edwin, Saunders, Mark P., Boot, Henk, Oppedijk, Vera, Dubbelman, Ria, Porritt, Bridget, Cats, Annemieke, Stroom, Joep, Valdes Olmos, Renato, Bartelink, Harry, and Verheij, Marcel. Thu . "Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer". United States. doi:10.1016/j.ijrobp.2006.09.012.
@article{osti_20944729,
title = {Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer},
author = {Jansen, Edwin and Saunders, Mark P. and Boot, Henk and Oppedijk, Vera and Dubbelman, Ria and Porritt, Bridget and Cats, Annemieke and Stroom, Joep and Valdes Olmos, Renato and Bartelink, Harry and Verheij, Marcel},
abstractNote = {Purpose: Postoperative chemoradiotherapy in gastric cancer improves locoregional control and survival. Reports on late toxicity, however, have been scarce thus far. Because renal toxicity is one of the most serious late complications in upper abdominal radiotherapy, we prospectively analyzed kidney function in patients who underwent postoperative chemoradiotherapy for gastric cancer. Patients and Methods: In 44 patients, Tc{sup 99m}-thiatide renography was performed before and at regular intervals after postoperative chemoradiotherapy. The left-to-right (L/R) ratio was used as an index of the relative kidney function. Mean L/R values were calculated for four follow-up time intervals. For all patients, kidney V{sub 20} (percentage of the volume of the kidney that received more than 20 Gy) and mean dose of both kidneys were retrieved from the three-dimensional dose-volume histograms. Results: We observed a progressive decrease in left renal function of 11% (p = 0.012) after 6 months, up to 52% (p < 0.001) after >18 months. The V{sub 20} (left kidney) and mean left kidney dose were identified as parameters associated with decreased kidney function. Mean serum creatinine was increased from 74.6 {mu}mol/L before treatment to 86.1 {mu}mol/L at 1 year after chemoradiotherapy (p < 0.001). In patients with a follow-up of 18-28 months, one case of severe renovascular hypertension was observed. Conclusion: A progressive relative functional impairment of the left kidney in patients after postoperative chemoradiotherapy for gastric cancer is demonstrated. To optimize the survival benefit that can be established with adjuvant regimens, strategies to minimize the dose to the kidneys and other critical organs should be explored.},
doi = {10.1016/j.ijrobp.2006.09.012},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 67,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 2007},
month = {Thu Mar 01 00:00:00 EST 2007}
}
  • Purpose: Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods: Between December 2000 and September 2003, 27 patients were treated at Tuebingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m{supmore » 2}), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m{sup 2}/24 h). A dose constraint of {<=}12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results: The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m{sup 2} in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range. Conclusions: Using a dose constraint of {<=}12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m{sup 2} administered before and after simultaneous 5-FU and radiotherapy.« less
  • Background: The Intergroup 0116 randomized study showed that postoperative 5-fluorouracil-based chemoradiotherapy improved locoregional control and overall survival in patients with gastric cancer. We hypothesized that these results could be improved further by using a more effective, intensified, and convenient chemotherapy schedule. Therefore, this Phase I-II dose-escalation study was performed to determine the maximal tolerated dose and toxicity profile of postoperative radiotherapy combined with concurrent capecitabine. Patients and Methods: After recovery from surgery for adenocarcinoma of the gastroesophageal junction or stomach, all patients were treated with capecitabine monotherapy, 1,000 mg/m{sup 2} twice daily for 2 weeks. After a 1-week treatment-free interval,more » patients received capecitabine (650-1,000 mg/m{sup 2} orally twice daily 5 days/week) in a dose-escalation schedule combined with radiotherapy on weekdays for 5 weeks. Radiotherapy was delivered to a total dose of 45 Gy in 25 fractions to the gastric bed, anastomoses, and regional lymph nodes. Results: Sixty-six patients were treated accordingly. Two patients went off study before or shortly after the start of chemoradiotherapy because of progressive disease. Therefore, 64 patients completed treatment as planned. During the chemoradiotherapy phase, 4 patients developed four items of Grade III dose-limiting toxicity (3 patients in Dose Level II and 1 patient in Dose Level IV). The predefined highest dose of capecitabine, 1,000 mg/m{sup 2} twice daily orally, was tolerated well and, therefore, considered safe for further clinical evaluation. Conclusions: This Phase I-II study shows that intensified chemoradiotherapy with daily capecitabine is feasible in postoperative patients with gastroesophageal junction and gastric cancer.« less
  • Purpose: Preoperative chemoradiotherapy (CRT) is superior to radiotherapy (RT) in locally advanced rectal cancer, but the survival gain is limited. Late toxicity is, therefore, important. The aim was to compare late bowel, urinary, and sexual functions after CRT or RT. Methods and Materials: Patients (N = 207) with nonresectable rectal cancer were randomized to preoperative CRT or RT (2 Gy Multiplication-Sign 25 {+-} 5-fluorouracil/leucovorin). Extended surgery was often required. Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer (EORTC) Quality of Lifemore » Questionnaire (QLQ-C30), International Index of Erectile Function (IIEF), and sexual function -vaginal changes questionnaire (SVQ). Results: Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up, 78 (74%) responded. More patients in the CRT group had received a stoma (73% vs. 52%, p = 0.09). Most patients without a stoma (7 of 12 in CRT group and 9 of 16 in RT group) had incontinence for liquid stools or gas. No stoma and good anal function were seen in 5 patients (11%) in the CRT group and in 11 (30%) in the RT group (p = 0.046). Of 44 patients in the CRT group, 12 (28%) had had bowel obstruction compared with 5 of 33 (15%) in the RT group (p = 0.27). One-quarter of the patients reported urinary incontinence. The majority of men had severe erectile dysfunction. Few women reported sexual activity during the previous month. However, the majority did not have concerns about their sex life. Conclusions: Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer. There was a clear tendency for the problems to be more common after CRT than after RT.« less
  • Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36-75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes atmore » 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m Superscript-Two ) followed by a bolus of 5-fluorouracil (400 mg/m Superscript-Two ) and then a 44-h continuous infusion of 5-fluorouracil (2400-3600 mg/m Superscript-Two ) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.« less
  • Purpose: To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity. Methods and Materials: A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy was performed before and at 12 and/or 24 months after RT.more » Pathologic findings such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were documented and correlated with the corresponding VRS. Results: Before RT, 99% had a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by VRS (p < 0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A significant coherence between the VRS and EORTC/RTOG was found (p < 0.01). Conclusions: The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the VRS was significantly more sensitive.« less