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Published in: Strahlentherapie und Onkologie 5/2013

01-05-2013 | Original article

Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

Authors: J. Boda-Heggemann, MD, PhD, C. Weiss, PhD, V. Schneider, MSc, R.-D. Hofheinz, MD, S. Haneder, MD, H. Michaely, MD, H. Wertz, U. Ronellenfitsch, MD, A. Hochhaus, MD, F. Wenz, MD, F. Lohr, MD

Published in: Strahlentherapie und Onkologie | Issue 5/2013

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Abstract

Purpose

In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy.

Patients and methods

Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS).

Results

Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47  %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44  %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed.

Conclusion

After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity.
Literature
1.
go back to reference Bleiberg H, Goffin JC, Dalesio O et al (1989) Adjuvant radiotherapy and chemotherapy in resectable gastric cancer. A randomized trial of the gastro-intestinal tract cancer cooperative group of the EORTC. Eur J Surg Oncol 15:535–543PubMed Bleiberg H, Goffin JC, Dalesio O et al (1989) Adjuvant radiotherapy and chemotherapy in resectable gastric cancer. A randomized trial of the gastro-intestinal tract cancer cooperative group of the EORTC. Eur J Surg Oncol 15:535–543PubMed
2.
go back to reference Macdonald JS, Smalley SR, Benedetti J et al (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730PubMedCrossRef Macdonald JS, Smalley SR, Benedetti J et al (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730PubMedCrossRef
3.
go back to reference Smalley SR, Benedetti JK, Haller DG et al (2012) Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol 30:2327–2333PubMedCrossRef Smalley SR, Benedetti JK, Haller DG et al (2012) Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol 30:2327–2333PubMedCrossRef
4.
go back to reference Kim S, Lim DH, Lee J et al (2005) An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach. Int J Radiat Oncol Biol Phys 63:1279–1285PubMedCrossRef Kim S, Lim DH, Lee J et al (2005) An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach. Int J Radiat Oncol Biol Phys 63:1279–1285PubMedCrossRef
5.
go back to reference Cunningham D, Allum WH, Stenning SP et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20PubMedCrossRef Cunningham D, Allum WH, Stenning SP et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20PubMedCrossRef
6.
go back to reference Ychou M, Boige V, Pignon JP et al (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29:1715–1721PubMedCrossRef Ychou M, Boige V, Pignon JP et al (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29:1715–1721PubMedCrossRef
7.
go back to reference Hagen P van, Hulshof MC, Lanschot JJ van et al (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366:2074–2084PubMedCrossRef Hagen P van, Hulshof MC, Lanschot JJ van et al (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366:2074–2084PubMedCrossRef
8.
go back to reference Leibl BJ, Vitz S, Schafer W et al (2011) Adenocarcinoma of the esophagogastric junction: neoadjuvant radiochemotherapy and radical surgery: early results and toxicity. Strahlenther Onkol 187:231–237PubMedCrossRef Leibl BJ, Vitz S, Schafer W et al (2011) Adenocarcinoma of the esophagogastric junction: neoadjuvant radiochemotherapy and radical surgery: early results and toxicity. Strahlenther Onkol 187:231–237PubMedCrossRef
9.
go back to reference Brunner T (2012) Despite of the updated analysis of the SWOG-directed Intergroup Study 0116, adjuvant radiochemotherapy is not yet the standard for gastric cancer after curative resection. Strahlenther Onkol 188(11):1052–1053PubMedCrossRef Brunner T (2012) Despite of the updated analysis of the SWOG-directed Intergroup Study 0116, adjuvant radiochemotherapy is not yet the standard for gastric cancer after curative resection. Strahlenther Onkol 188(11):1052–1053PubMedCrossRef
10.
go back to reference Lordick F (2012) Value of postoperative radiochemotherapy after completely resected gastric cancer not definitive despite negative overall results of the ARTIST trial. Strahlenther Onkol 188:636–637PubMedCrossRef Lordick F (2012) Value of postoperative radiochemotherapy after completely resected gastric cancer not definitive despite negative overall results of the ARTIST trial. Strahlenther Onkol 188:636–637PubMedCrossRef
11.
go back to reference Guckenberger M (2012) Indications for neoadjuvant or definitive radiochemotherapy in esophageal cancer of the highest evidence quality. Strahlenther Onkol 188:949–950PubMedCrossRef Guckenberger M (2012) Indications for neoadjuvant or definitive radiochemotherapy in esophageal cancer of the highest evidence quality. Strahlenther Onkol 188:949–950PubMedCrossRef
12.
go back to reference Smalley SR, Gunderson L, Tepper J et al (2002) Gastric surgical adjuvant radiotherapy consensus report: rationale and treatment implementation. Int J Radiat Oncol Biol Phys 52:283–293PubMedCrossRef Smalley SR, Gunderson L, Tepper J et al (2002) Gastric surgical adjuvant radiotherapy consensus report: rationale and treatment implementation. Int J Radiat Oncol Biol Phys 52:283–293PubMedCrossRef
13.
go back to reference Hofheinz RD, Wenz F, Lukan N et al (2009) Oxaliplatin and capecitabine-based chemoradiotherapy for gastric cancer–an extended phase I MARGIT and AIO trial. Int J Radiat Oncol Biol Phys 73:142–147PubMedCrossRef Hofheinz RD, Wenz F, Lukan N et al (2009) Oxaliplatin and capecitabine-based chemoradiotherapy for gastric cancer–an extended phase I MARGIT and AIO trial. Int J Radiat Oncol Biol Phys 73:142–147PubMedCrossRef
14.
go back to reference Boda-Heggemann J, Hofheinz RD, Weiss C et al (2009) Combined adjuvant radiochemotherapy with IMRT/XELOX improves outcome with low renal toxicity in gastric cancer. Int J Radiat Oncol Biol Phys 75:1187–1195PubMedCrossRef Boda-Heggemann J, Hofheinz RD, Weiss C et al (2009) Combined adjuvant radiochemotherapy with IMRT/XELOX improves outcome with low renal toxicity in gastric cancer. Int J Radiat Oncol Biol Phys 75:1187–1195PubMedCrossRef
15.
go back to reference Jansen EP, Saunders MP, Boot H et al (2007) Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer. Int J Radiat Oncol Biol Phys 67:781–785PubMedCrossRef Jansen EP, Saunders MP, Boot H et al (2007) Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer. Int J Radiat Oncol Biol Phys 67:781–785PubMedCrossRef
16.
go back to reference Welz S, Hehr T, Kollmannsberger C et al (2007) Renal toxicity of adjuvant chemoradiotherapy with cisplatin in gastric cancer. Int J Radiat Oncol Biol Phys 69:1429–1435PubMedCrossRef Welz S, Hehr T, Kollmannsberger C et al (2007) Renal toxicity of adjuvant chemoradiotherapy with cisplatin in gastric cancer. Int J Radiat Oncol Biol Phys 69:1429–1435PubMedCrossRef
17.
go back to reference Gunderson LL, Sosin H (1982) Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 8:1–11PubMedCrossRef Gunderson LL, Sosin H (1982) Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 8:1–11PubMedCrossRef
18.
go back to reference Lohr F, Dobler B, Mai S et al (2003) Optimization of dose distributions for adjuvant locoregional radiotherapy of gastric cancer by IMRT. Strahlenther Onkol 179:557–563PubMedCrossRef Lohr F, Dobler B, Mai S et al (2003) Optimization of dose distributions for adjuvant locoregional radiotherapy of gastric cancer by IMRT. Strahlenther Onkol 179:557–563PubMedCrossRef
19.
go back to reference Wieland P, Dobler B, Mai S et al (2004) IMRT for postoperative treatment of gastric cancer: covering large target volumes in the upper abdomen: a comparison of a step-and-shoot and an arc therapy approach. Int J Radiat Oncol Biol Phys 59:1236–1244PubMedCrossRef Wieland P, Dobler B, Mai S et al (2004) IMRT for postoperative treatment of gastric cancer: covering large target volumes in the upper abdomen: a comparison of a step-and-shoot and an arc therapy approach. Int J Radiat Oncol Biol Phys 59:1236–1244PubMedCrossRef
20.
go back to reference Hofheinz RD, Wenz F, Lukan N et al (2008) Oxaliplatin and capecitabine-based chemoradiotherapy for gastric cancer-an extended phase I MARGIT and AIO trial. Int J Radiat Oncol Biol Phys 73(1):142–147PubMedCrossRef Hofheinz RD, Wenz F, Lukan N et al (2008) Oxaliplatin and capecitabine-based chemoradiotherapy for gastric cancer-an extended phase I MARGIT and AIO trial. Int J Radiat Oncol Biol Phys 73(1):142–147PubMedCrossRef
21.
go back to reference Sakuramoto S, Sasako M, Yamaguchi T et al (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820PubMedCrossRef Sakuramoto S, Sasako M, Yamaguchi T et al (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820PubMedCrossRef
22.
go back to reference Bang YJ, Kim YW, Yang HK et al (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379:315–321PubMedCrossRef Bang YJ, Kim YW, Yang HK et al (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379:315–321PubMedCrossRef
23.
go back to reference Stahl M, Walz MK, Stuschke M et al (2009) Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 27:851–856PubMedCrossRef Stahl M, Walz MK, Stuschke M et al (2009) Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 27:851–856PubMedCrossRef
24.
go back to reference Buergy D, Lohr F, Baack T et al (2012) Radiotherapy for tumors of the stomach and gastroesophageal junction—a review of its role in multimodal therapy. Radiat Oncol 7:192PubMedCrossRef Buergy D, Lohr F, Baack T et al (2012) Radiotherapy for tumors of the stomach and gastroesophageal junction—a review of its role in multimodal therapy. Radiat Oncol 7:192PubMedCrossRef
25.
go back to reference Schuhmacher CP, Fink U, Becker K et al (2001) Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up. Cancer 91:918–927PubMedCrossRef Schuhmacher CP, Fink U, Becker K et al (2001) Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up. Cancer 91:918–927PubMedCrossRef
26.
go back to reference Haneder S, Michaely HJ, Schoenberg SO et al (2012) Assessment of renal function after conformal radiotherapy and intensity-modulated radiotherapy by functional (1)H-MRI and (23)Na-MRI. Strahlenther Onkol 188:1146–1154PubMedCrossRef Haneder S, Michaely HJ, Schoenberg SO et al (2012) Assessment of renal function after conformal radiotherapy and intensity-modulated radiotherapy by functional (1)H-MRI and (23)Na-MRI. Strahlenther Onkol 188:1146–1154PubMedCrossRef
27.
go back to reference Lee J, Lim do H, Kim S et al (2012) Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol 30:268–273PubMedCrossRef Lee J, Lim do H, Kim S et al (2012) Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol 30:268–273PubMedCrossRef
Metadata
Title
Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer
Authors
J. Boda-Heggemann, MD, PhD
C. Weiss, PhD
V. Schneider, MSc
R.-D. Hofheinz, MD
S. Haneder, MD
H. Michaely, MD
H. Wertz
U. Ronellenfitsch, MD
A. Hochhaus, MD
F. Wenz, MD
F. Lohr, MD
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Strahlentherapie und Onkologie / Issue 5/2013
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-013-0309-2

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