Abstract
The use of radiotherapy for treatment of gastric cancer has become commonplace over the past 10 years following reporting of the US Intergroup Trial 0116. However, gastric irradiation has proved to be very challenging for radiation oncologists. Aside from the technical difficulties associated with radiotherapy, there are also many clinical challenges faced by clinicians when deciding optimal treatment for patients with gastric cancer. With increasing use of perioperative chemotherapy and more extensive surgical resection, the indications for radiotherapy have become less well defined. Radiation oncologists are also wary of the acute and potential late toxicities associated with abdominal irradiation. This chapter will describe the challenges faced by radiation oncologists when treating gastric cancer and summarise the available evidence regarding prognostic and predictive factors for survival, response and toxicity after radiotherapy.
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Ajani JA, Mansfield PF, Janjan N, Morris J, Pisters PW, Lynch PM, Feig B, Myerson R, Nivers R, Cohen DS, Gunderson LL (2004) Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol 22(14):2774–2780
Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA (2006) 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 24(24):3953–3958
Alani S, Soyfer V, Strauss N, Schifter D, Corn BW (2009) Limited advantages of intensity-modulated radiotherapy over 3D conformal radiation therapy in the adjuvant management of gastric cancer. Int J Radiat Oncol Biol Phys 74(2):562–566. doi:10.1016/j.ijrobp.2008.09.061
Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Ji J, Yeh TS, Button P, Sirzen F, Noh SH (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379(9813):315–321. doi:10.1016/S0140-6736(11)61873-4
Bell LA, Ryan KM (2004) Life and death decisions by E2F–1. Cell Death Differ 11(2):137–142. doi:10.1038/sj.cdd.4401324
Bonenkamp JJ, Hermans J, Sasako M, van de Velde CJ (1999) Extended lymph-node dissection for gastric cancer. Dutch gastric cancer group. N Engl J Med 340(12):908–914
Buffart TE, van Grieken NC, Tijssen M, Coffa J, Ylstra B, Grabsch HI, van de Velde CJ, Carvalho B, Meijer GA (2009) High resolution analysis of DNA copy-number aberrations of chromosomes 8, 13, and 20 in gastric cancers. Virchows Archiv Int J pathol 455(3):213–223. doi:10.1007/s00428-009-0814-y
Bunt AM, Hermans J, Smit VT, van de Velde CJ, Fleuren GJ, Bruijn JA (1995) Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries. J Clin Oncol 13(1):19–25
Chakravarty T, Crane CH, Ajani JA, Mansfield PF, Briere TM, Beddar AS, Mok H, Reed VK, Krishnan S, Delclos ME, Das P (2012) Intensity-modulated radiation therapy with concurrent chemotherapy as preoperative treatment for localized gastric adenocarcinoma. Int J Radiat Oncol Biol Phys 83(2):581–586. doi:10.1016/j.ijrobp.2011.07.035
Chang AT, Ng WT, Law AL, Ku KM, Lee MC, Lee AW (2011) Adjuvant chemoradiation for resected gastric cancer: a 10 year experience. Gastric Cancer 14(1):63–71. doi:10.1007/s10120-011-0011-y
Cheng JC, Wu JK, Lee PC, Liu HS, Jian JJ, Lin YM, Sung JL, Jan GJ (2004) Biologic susceptibility of hepatocellular carcinoma patients treated with radiotherapy to radiation-induced liver disease. Int J Radiat Oncol Biol Phys 60(5):1502–1509. doi:10.1016/j.ijrobp.2004.05.048
Cunningham D, Allum WH, Stenning SP, Thompson JN, van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, Participants MT (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355(1):11–20
Cuschieri A, Weeden S, Fielding J, Bancewicz J, Craven J, Joypaul V, Sydes M, Fayers P (1999) Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical co-operative group. Br J Cancer 79(9–10):1522–1530
Dahele M, Skinner M, Schultz B, Cardoso M, Bell C, Ung YC (2010) Adjuvant radiotherapy for gastric cancer: A dosimetric comparison of 3-dimensional conformal radiotherapy, tomotherapy and conventional intensity modulated radiotherapy treatment plans. Med Dosim 35(2):115–121. doi:10.1016/j.meddos.2009.03.003
Dawson LA, Kavanagh BD, Paulino AC, Das SK, Miften M, Li XA, Pan C, Ten Haken RK, Schultheiss TE (2010) Radiation-associated kidney injury. Int J Radiat Oncol Biol Phys 76(3):S108–S115. doi:10.1016/j.ijrobp.2009.02.089
Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK (2002) Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 53(4):810–821
Dawson LA, Ten Haken RK, Lawrence TS (2001) Partial irradiation of the liver. Semin Radiat Oncol 11(3):240–246
Dikken JL, van de Velde CJ, Gonen M, Verheij M, Brennan MF, Coit DG (2012) The new American joint committee on cancer/international union against cancer staging system for adenocarcinoma of the stomach: increased complexity without clear improvement in predictive accuracy. Ann Surg Oncol 19(8):2443–2451. doi:10.1245/s10434-012-2403-6
Edge SB, Byrd DR, Compton CC et al (2009) American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging manual, 7th edn. Springer, Berlin Heidelberg New York
Fuchs CS, Tepper JE, Niedzwiecki D, Hollis D, Mamon HJ, Swanson R, Haller DG, Dragovich T, Alberts SR, Bjarnason GA, Willett CG, Enzinger PC, Goldberg RM, Venook AP, Mayer RJ (2011) Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and after CRT: intergroup trial CALGB 80101. J Clin Oncol 29(15):4003
Guggenheim DE, Shah MA (2012) Gastric cancer epidemiology and risk factors. J Surg Oncol. doi:10.1002/jso.23262
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):1–11
Han DS, Suh YS, Kong SH, Lee HJ, Choi Y, Aikou S, Sano T, Park BJ, Kim WH, Yang HK (2012) Nomogram predicting long-term survival after D2 gastrectomy for gastric cancer. J Clin Oncol 30(31):3834–3840. doi:10.1200/JCO.2012.41.8343
Jansen EP, Saunders MP, Boot H, Oppedijk V, Dubbelman R, Porritt B, Cats A, Stroom J, Valdes Olmos R, Bartelink H, Verheij M (2007) Prospective study on late renal toxicity following postoperative chemoradiotherapy in gastric cancer. Int J Radiat Oncol Biol Phys 67(3):781–785. doi:10.1016/j.ijrobp.2006.09.012
Kassam Z, Lockwood G, O’Brien C, Brierley J, Swallow C, Oza A, Siu L, Knox JJ, Wong R, Cummings B, Kim J, Moore M, Ringash J (2006) Conformal radiotherapy in the adjuvant treatment of gastric cancer: review of 82 cases. Int J Radiat Oncol Biol Phys 65(3):713–719. doi:10.1016/j.ijrobp.2006.01.001
Kattan MW, Karpeh MS, Mazumdar M, Brennan MF (2003) Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma. J Clin Oncol 21(19):3647–3650. doi:10.1200/JCO.2003.01.240
Kim TH, Kim DY, Park JW, Kim SH, Choi JI, Kim HB, Lee WJ, Park SJ, Hong EK, Kim CM (2007) Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 67(1):225–231. doi:10.1016/j.ijrobp.2006.08.015
Koc M, Dizen H, Ozalp N, Keskek M, Karakose N, Tez M (2009) External validation of a US-derived nomogram that predicts individual survival after gastric cancer resection. Langenbeck’s Arch Surg 394(4):755–756. doi:10.1007/s00423-008-0426-z
Kundel Y, Purim O, Idelevich E, Lavrenkov K, Man S, Kovel S, Karminsky N, Pfeffer RM, Nisenbaum B, Fenig E, Sulkes A, Brenner B (2011) Postoperative chemoradiation for resected gastric cancer–is the Macdonald regimen tolerable? a retrospective multi-institutional study. Radiat Oncol 6:127. doi:10.1186/1748-717X-6-127
La Thangue NB (2003) The yin and yang of E2F–1: balancing life and death. Nature Cell Biol 5(7):587–589. doi:10.1038/ncb0703-587
Lee J, Park CK, Park JO, Lim T, Park YS, Lim HY, Lee I, Sohn TS, Noh JH, Heo JS, Kim S, Lim do H, Kim KM, Kang WK (2008) Impact of E2F–1 expression on clinical outcome of gastric adenocarcinoma patients with adjuvant chemoradiation therapy. Clin Cancer Res 14(1):82–88. doi:10.1158/1078-0432.CCR-07-0612
Leong T, Joon DL, Willis D, Jayamoham J, Spry N, Harvey J, Di Iulio J, Milner A, Mann GB, Michael M (2011) Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys 79(3):690–695. doi:10.1016/j.ijrobp.2009.11.042
Leong T, Smithers M, Michael M, Gebski V, Boussioutas A, Miller D, Zalcberg JR, Wong R, Haustermans K (2012) TOPGEAR: An international randomized phase III trial of preoperative chemoradiotherapy versus preoperative chemotherapy for resectable gastric cancer (AGITG/TROG/EORTC/NCIC CTG). J Clin Oncol 30(15) (May 20 Supplement):TPS4141
Leong T, Willis D, Joon DL, Condron S, Hui A, Ngan SY (2005) 3D Conformal radiotherapy for gastric cancer-results of a comparative planning study. Radiother Oncol 74(3):301–306
Li SG, Ye ZY, Zhao ZS, Tao HQ, Wang YY, Niu CY (2008) Correlation of integrin beta3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma. World J Gastroenterol 14(3):421–427
Liang SX, Zhu XD, Xu ZY, Zhu J, Zhao JD, Lu HJ, Yang YL, Chen L, Wang AY, Fu XL, Jiang GL (2006) Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: the risk factors and hepatic radiation tolerance. Int J Radiat Oncol Biol Phys 65(2):426–434. doi:10.1016/j.ijrobp.2005.12.031
MacDonald JS (2011) Gastric Cancer: Nagoya is not New York. J Clin Oncol 29(33):4348–4350
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345(10):725–730
Marchet A, Mocellin S, Belluco C, Ambrosi A, DeMarchi F, Mammano E, Digito M, Leon A, D’Arrigo A, Lise M, Nitti D (2007) Gene expression profile of primary gastric cancer: towards the prediction of lymph node status. Ann Surg Oncol 14(3):1058–1064. doi:10.1245/s10434-006-9090-0
May KS, Khushalani NI, Chandrasekhar R, Wilding GE, Iyer RV, Ma WW, Flaherty L, Russo RC, Fakih M, Kuvshinoff BW, Gibbs JF, Javle MM, Yang GY (2010) Analysis of clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen. Int J Radiat Oncol Biol Phys 76(4):1193–1198. doi:10.1016/j.ijrobp.2009.03.002
Minn AY, Hsu A, La T, Kunz P, Fisher GA, Ford JM, Norton JA, Visser B, Goodman KA, Koong AC, Chang DT (2010) Comparison of intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy as adjuvant therapy for gastric cancer. Cancer 116(16):3943–3952. doi:10.1002/cncr.25246
Mutze K, Langer R, Schumacher F, Becker K, Ott K, Novotny A, Hapfelmeier A, Hofler H, Keller G (2011) DNA methyltransferase 1 as a predictive biomarker and potential therapeutic target for chemotherapy in gastric cancer. Eur J Cancer 47(12):1817–1825. doi:10.1016/j.ejca.2011.02.024
Novotny AR, Schuhmacher C, Busch R, Kattan MW, Brennan MF, Siewert JR (2006) Predicting individual survival after gastric cancer resection: validation of a US-derived nomogram at a single high-volume center in Europe. Ann Surg 243(1):74–81
Osti MF, Agolli L, Bracci S, Monaco F, Tubin S, Minniti G, De Sanctis V, Enrici RM (2012) Adjuvant chemoradiation with 5-fluorouracil or capecitabine in patients with gastric cancer after D2 nodal dissection. Anticancer Res 32(4):1397–1402
Pan CC, Kavanagh BD, Dawson LA, Li XA, Das SK, Miften M, Ten Haken RK (2010) Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 76(3 Suppl):S94–S100. doi:10.1016/j.ijrobp.2009.06.092
Patel PR, Mansfield PF, Crane CH, Wu TT, Lee JH, Lynch PM, Morris J, Pisters PW, Feig B, Sunder PK, Izzo JG, Ajani JA (2007) Clinical stage after preoperative chemoradiation is a better predictor of patient outcome than the baseline stage for localized gastric cancer. Cancer 110(5):989–995. doi:10.1002/cncr.22870
Peeters KC, Kattan MW, Hartgrink HH, Kranenbarg EK, Karpeh MS, Brennan MF, van de Velde CJ (2005) Validation of a nomogram for predicting disease-specific survival after an R0 resection for gastric carcinoma. Cancer 103(4):702–707. doi:10.1002/cncr.20783
Quero L, Bouchbika Z, Kouto H, Baruch-Hennequin V, Gornet JM, Munoz N, Cojean-Zelek I, Houdart R, Panis Y, Valleur P, Aparicio T, Maylin C, Hennequin C (2012) Postoperative chemotherapy followed by conformal concomitant chemoradiotherapy in high-risk gastric cancer. Int J Radiat Oncol Biol Phys 83(2):574–580. doi:10.1016/j.ijrobp.2011.07.031
Reed VK, Krishnan S, Mansfield PF, Bhosale PR, Kim M, Das P, Janjan NA, Delclos ME, Lowy AM, Feig BW, Pisters PW, Ajani JA, Crane CH (2008) Incidence, natural history, and patterns of locoregional recurrence in gastric cancer patients treated with preoperative chemoradiotherapy. Int J Radiat Oncol Biol Phys 71(3):741–747. doi:10.1016/j.ijrobp.2007.10.030
Robb WB, Mariette C (2012) Predicting the response to chemotherapy in gastric adenocarcinoma: who benefits from neoadjuvant chemotherapy? Recent Res Cancer Res 196:241–268. doi:10.1007/978-3-642-31629-6_17
Rohatgi PR, Mansfield PF, Crane CH, Wu TT, Sunder PK, Ross WA, Morris JS, Pisters PW, Feig BW, Gunderson LL, Ajani JA (2006) Surgical pathology stage by American Joint Commission on cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma. Cancer 107(7):1475–1482. doi:10.1002/cncr.22180
Rostom Y, Zaghloul H, Khedr G, El-Shazly W, Abd-Allah D (2012) Docetaxel-based preoperative chemoradiation in localized gastric cancer: impact of pathological complete response on patient outcome. J Gastrointest Cancer. doi:10.1007/s12029-012-9449-3
Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. New Engl J Med 357(18):1810–1820. doi:10.1056/NEJMoa072252
Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS (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(19):2327–2333. doi:10.1200/JCO.2011.36.7136
Smalley SR, Gunderson L, Tepper J, Martenson JA, Minsky B, Willett C, Rich T (2002) Gastric surgical adjuvant radiotherapy consensus report: rationale and treatment implementation. Int J Radiat Oncol Biol Phys 52(2):283–293
Soyuer S, Soyuer I, Unal D, Ucar K, Yildiz OG, Orhan O (2010) Prognostic significance of CD9 expression in locally advanced gastric cancer treated with surgery and adjuvant chemoradiotherapy. Pathol Res Pract 206(9):607–610. doi:10.1016/j.prp.2010.04.004
Stewart FA, Oussoren Y, Bartelink H (1989) The influence of cisplatin on the response of mouse kidneys to multifraction irradiation. Radiother Oncol 15(1):93–102
Strong VE, Song KY, Park CH, Jacks LM, Gonen M, Shah M, Coit DG, Brennan MF (2010) Comparison of gastric cancer survival following R0 resection in the United States and Korea using an internationally validated nomogram. Ann Surg 251(4):640–646. doi:10.1097/SLA.0b013e3181d3d29b
Tarbell NJ, Guinan EC, Niemeyer C, Mauch P, Sallan SE, Weinstein HJ (1988) Late onset of renal dysfunction in survivors of bone marrow transplantation. Int J Radiat Oncol Biol Phys 15(1):99–104
Teramoto K, Tada M, Tamoto E, Abe M, Kawakami A, Komuro K, Matsunaga A, Shindoh G, Takada M, Murakawa K, Kanai M, Kobayashi N, Fujiwara Y, Nishimura N, Shirata K, Takahishi T, Ishizu A, Ikeda H, Hamada J, Kondo S, Katoh H, Moriuchi T, Yoshiki T (2005) Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiling. J Surg Res 124(2):225–236. doi:10.1016/j.jss.2004.10.003
Tillman GF, Pawlicki T, Koong AC, Goodman KA (2008) Preoperative versus postoperative radiotherapy for locally advanced gastroesophageal junction and proximal gastric cancers: a comparison of normal tissue radiation doses. Dis Esophagus 21(5):437–444. doi:10.1111/j.1442-2050.2007.00794.x
Van Cutsem E, de Haas S, Kang YK, Ohtsu A, Tebbutt NC, Ming XuJ, Peng Yong W, Langer B, Delmar P, Scherer SJ, Shah MA (2012) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol 30(17):2119–2127. doi:10.1200/JCO.2011.39.9824
Verdecchia A, Mariotto A, Gatta G, Bustamante-Teixeira MT, Ajiki W (2003) Comparison of stomach cancer incidence and survival in four continents. Eur J Cancer 39(11):1603–1609
Verheij M, Dikken J, Coit D, Baser R, Gonen M, Goodman K, Brennan M, Jansen E, Boot H, van de Velde C (2012) Performance of a nomogram predicting disease-specific survival after an R0 resection for gastric cancer in patients receiving postoperative chemoradiation therapy. Int J Radiat Oncol Biol Phys 84(3):S194
Wang S, Wu X, Chen Y, Zhang J, Ding J, Zhou Y, He S, Tan Y, Qiang F, Bai J, Zeng J, Gong Z, Li A, Li G, Roe OD, Zhou J (2012) Prognostic and predictive role of JWA and XRCC1 expressions in gastric cancer. Clin Cancer Res 18(10):2987–2996. doi:10.1158/1078-0432.CCR-11-2863
Wu L, Timmers C, Maiti B, Saavedra HI, Sang L, Chong GT, Nuckolls F, Giangrande P, Wright FA, Field SJ, Greenberg ME, Orkin S, Nevins JR, Robinson ML, Leone G (2001) The E2F1-3 transcription factors are essential for cellular proliferation. Nature 414(6862):457–462. doi:10.1038/35106593
Wu Y, Guo E, Yu J, Xie Q (2008) High DcR3 expression predicts stage pN2-3 in gastric cancer. Am J Clin Oncol 31(1):79–83. doi:10.1097/COC.0b013e3180ca77ad
Zhang ZX, Gu XZ, Yin WB, Huang GJ, Zhang DW, Zhang RG (1998) 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 42(5):929–934
Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, Tsuneyama K, Takano Y (2006) Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res 26 (5A):3579–3583
Zhu WG, Xua DF, Pu J, Zong CD, Li T, Tao GZ, Ji FZ, Zhou XL, Han JH, Wang CS, Yu CH, Yi JG, Su XL, Ding JX (2012) A randomized, controlled, multicenter study comparing intensity-modulated radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric cancer patients with D2 resection. Radiother Oncol 104(3):361–366. doi:10.1016/j.radonc.2012.08.024
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Leong, T. (2013). Gastric Cancer. In: Nieder, C., Gaspar, L. (eds) Decision Tools for Radiation Oncology. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2013_829
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