Preoperative chemoradiotherapy for locally advanced gastric cancer

Radiation Oncology

Brian G Czito³  Hope E Uronis²  Douglas S Tyler¹  Dan G Blazer III¹  Manisha Palta³  Christopher G Willett³  Junzo P Chino³  Joseph M Pepek³ 

[1] Department of Surgery, Duke University School of Medicine, Durham, NC, USA;Department of Medicine, Division of Medical Oncology, Duke University School of Medicine, Durham, NC, USA;Department of Radiation Oncology, Duke University School of Medicine, Box 3085, Durham, NC, 27710, USA

关键词: Neoadjuvant;    Chemoradiotherapy;    Gastric cancer;   

Others  :  1154775
DOI  :  10.1186/1748-717X-8-6

 received in 2012-09-10, accepted in 2012-12-28,  发布年份 2013

【 摘 要 】

Background

To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer.

Methods

Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0.

Results

Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively.

Conclusions

Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

【 授权许可】

   
2013 Pepek et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001, 345:725-730.
• [2]Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006, 355:11-20.
• [3]Bang YJ, Kim YW, Yang HK, et al.: Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 2012, 379:315-321.
• [4]Lee J, Lim Do H, Kim S, et al.: 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 2012, 30:268-273.
• [5]Walsh TN, Noonan N, Hollywood D, et al.: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996, 335:462-467.
• [6]Urba SG, Orringer MB, Turrisi A, et al.: Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001, 19:305-313.
• [7]Tepper J, Krasna MJ, Niedzwiecki D, et al.: Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 2008, 26:1086-1092.
• [8]van Hagen P, Hulshof MC, van Lanschot JJ, et al.: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012, 366:2074-2084.
• [9]Sauer R, Becker H, Hohenberger W, et al.: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004, 351:1731-1740.
• [10]Allum WH, Hallissey MT, Ward LC, et al.: A controlled, prospective, randomised trial of adjuvant chemotherapy or radiotherapy in resectable gastric cancer: interim report. British Stomach Cancer Group. Br J Cancer 1989, 60:739-744.
• [11]Zhang ZX, Gu XZ, Yin WB, et al.: Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)–report on 370 patients. Int J Radiat Oncol Biol Phys 1998, 42:929-934.
• [12]Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 2006, 24:3953-3958.
• [13]Ajani JA, Mansfield PF, Crane CH, et al.: Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol 2005, 23:1237-1244.
• [14]Ajani JA, Mansfield PF, Janjan N, et al.: Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol 2004, 22:2774-2780.
• [15]Reed VK, Krishnan S, Mansfield PF, et al.: Incidence, natural history, and patterns of locoregional recurrence in gastric cancer patients treated with preoperative chemoradiotherapy. Int J Radiat Oncol Biol Phys 2008, 71:741-747.
• [16]Fields RC, Strong VE, Gonen M, et al.: Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma. Br J Cancer 2011, 104:1840-1847.
• [17]Diaz-Gonzalez JA, Rodriguez J, Hernandez-Lizoain JL, et al.: Patterns of response after preoperative treatment in gastric cancer. Int J Radiat Oncol Biol Phys 2011, 80:698-704.
• [18]Siewert JR, Stein HJ: Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg 1998, 85:1457-1459.
• [19]Matzinger O, Gerber E, Bernstein Z, et al.: EORTC-ROG expert opinion: radiotherapy volume and treatment guidelines for neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction and the stomach. Radiother Oncol 2009, 92:164-175.
• [20]Horn RC Jr: Carcinoma of the stomach; autopsy findings in untreated cases. Gastroenterology 29:515-523. discussion, 523–5, 1955
• [21]Gunderson LL, Sosin H: 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 1982, 8:1-11.
• [22]Landry J, Tepper JE, Wood WC, et al.: Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys 1990, 19:1357-1362.
• [23]Papachristou DN, Fortner JG: Local recurrence of gastric adenocarcinomas after gastrectomy. J Surg Oncol 1981, 18:47-53.
• [24]Lowy AM, Feig BW, Janjan N, et al.: A pilot study of preoperative chemoradiotherapy for resectable gastric cancer. Ann Surg Oncol 2001, 8:519-524.
• [25]Bonenkamp JJ, Songun I, Hermans J, et al.: Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 1995, 345:745-748.
• [26]Mariette C, Seitz JF, Maillard E, et al.: Surgery alone versus chemoradiotherapy followed by surgery for localized esophageal cancer: Analysis of a randomized controlled phase III trial FFCD 9901. J Clin Oncol 2010, 28:15s.
• [27]Stahl M, Walz MK, Stuschke M, et al.: Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 2009, 27:851-856.
• [28]Atkins BZ, Shah AS, Hutcheson KA, et al.: Reducing hospital morbidity and mortality following esophagectomy. Ann Thorac Surg 2004, 78:1170-1176. discussion 1170–6
• [29]Wanebo HJ, Kennedy BJ, Chmiel J, et al.: Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg 1993, 218:583-592.
• [30]Bonenkamp JJ, Hermans J, Sasako M, et al.: Extended lymph-node dissection for gastric cancer. N Engl J Med 1999, 340:908-914.
• [31]Piessen G, Messager M, Leteurtre E, et al.: Signet ring cell histology is an independent predictor of poor prognosis in gastric adenocarcinoma regardless of tumoral clinical presentation. Ann Surg 2009, 250:878-887.
• [32]Schuhmacher C, Gretschel S, Lordick F, et al.: Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: european organisation for research and treatment of cancer randomized trial 40954. J Clin Oncol 2010, 28:5210-5218.
• [33]Becker K, Langer R, Reim D, et al.: Significance of histopathological tumor regression after neoadjuvant chemotherapy in gastric adenocarcinomas: a summary of 480 cases. Ann Surg 2011, 253:934-939.
• [34]Chen J, Cheong JH, Yun MJ, et al.: Improvement in preoperative staging of gastric adenocarcinoma with positron emission tomography. Cancer 2005, 103:2383-2390.
• [35]Lowy AM, Mansfield PF, Leach SD, et al.: Laparoscopic staging for gastric cancer. Surgery 1996, 119:611-614.
• [36]Burke EC, Karpeh MS, Conlon KC, et al.: Laparoscopy in the management of gastric adenocarcinoma. Ann Surg 1997, 225:262-267.
• [37]Smith DD, Schwarz RR, Schwarz RE: Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database. J Clin Oncol 2005, 23:7114-7124.
• [38]Siewert JR, Bottcher K, Stein HJ, et al.: Relevant prognostic factors in gastric cancer: ten-year results of the german gastric cancer study. Ann Surg 1998, 228:449-461.