Clinical management of gastroesophageal junction tumors: past and recent evidences for the role of radiotherapy in the multidisciplinary approach

Radiation Oncology

Vincenzo Valentini²  Gian Carlo Mattiucci²  Francesco M Di Matteo¹  Alessio G Morganti²  Francesco Cellini³ 

[1] GI Endoscopy Unit, Policlinico Universitario Campus Bio-Medico University, Via Alvaro del Portillo 200, 00128 Rome, Italy;Radiation Oncology Department, Policlinico Universitario “A. Gemelli”, Universita` Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Rome, Italy;Radiation Oncology, Policlinico Universitario Campus Bio-Medico, Via Álvaro del Portillo, 200, 00144 Rome, Italy

关键词: Management;    Chemotherapy;    Tumor;    Chemoradiation;    Radiochemotherapy;    Radiotherapy;    Review;    Esophageal;    Gastric;    Gastroesophageal;   

Others  :  814830
DOI  :  10.1186/1748-717X-9-45

 received in 2013-10-31, accepted in 2014-02-01,  发布年份 2014

【 摘 要 】

Gastroesophageal cancers (such as esophageal, gastric and gastroesophageal-junction -GEJ- lesions) are worldwide a leading cause of death being relatively rare but highly aggressive. In the past years, a clear shift in the location of upper gastrointestinal tract tumors has been recorded, both affecting the scientific research and the modern clinical practice. The integration of pre- or peri-operative multimodal approaches, as radiotherapy and chemotherapy (often combined), seems promising to further improve clinical outcome for such presentations. In the past, the definition of GEJ led to controversies and confusion: GEJ tumors have been managed either grouped to gastric or esophageal lesions, following slightly different surgical, radiotherapeutic and systemic approaches. Recently, the American Joint Committee on Cancer (AJCC) changed the staging and classification system of GEJ to harmonize some staging issues for esophageal and gastric cancer. This review discusses the most relevant historical and recent evidences of neoadjuvant treatment involving Radiotherapy for GEJ tumors, and describes the efficacy of such treatment in the frame of multimodal integrated therapies, from the new point of view of the recent classification of such tumors.

【 授权许可】

   
2014 Cellini et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]NCCN: NCCN guidelines - esophageal and esophagogastric cancers (excluding proximal 5 cm stomach). NCCN clinical practice guideline in oncology - version 2.2013Available at:http://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf webcite
• [2]Moehler M, Gockel I, Roessler HP, Arnold D, Trarbach T, Thomaidis T, Klautke G, Rodel C, Brenner B, Lang H, et al.: Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction. BMC Cancer 2013, 13:75. BioMed Central Full Text
• [3]Yang L, Wang LS, Chen XL, Gatalica Z, Qiu S, Liu Z, Stoner G, Zhang H, Weiss H, Xie J: Hedgehog signaling activation in the development of squamous cell carcinoma and adenocarcinoma of esophagus. Int J Biochem Mol Biol 2012, 3:46-57.
• [4]Cellini F, Valentini V: Targeted therapies in combination with radiotherapy in oesophageal and gastroesophageal carcinoma. Curr Med Chem 2013. [Epub ahead of print]
• [5]Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr: Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991, 265:1287-1289.
• [6]PDQ: PDQ® Gastric cancer treatment. Bethesda, MD: National Cancer Institute. Date last modified 02/15/2013. Available at: http://cancer.gov/cancertopics/pdq/treatment/gastric/HealthProfessional webcite
• [7]Crew KD, Neugut AI: Epidemiology of upper gastrointestinal malignancies. Semin Oncol 2004, 31:450-464.
• [8]Powell J, McConkey CC, Gillison EW, Spychal RT: Continuing rising trend in oesophageal adenocarcinoma. Int J Cancer 2002, 102:422-427.
• [9]Rusch VW: Are cancers of the esophagus, gastroesophageal junction, and cardia one disease, two, or several? Semin Oncol 2004, 31:444-449.
• [10]Buas MF, Vaughan TL: Epidemiology and risk factors for gastroesophageal junction tumors: understanding the rising incidence of this disease. Semin Radiat Oncol 2013, 23:3-9.
• [11]Devesa SS, Fraumeni JF Jr: The rising incidence of gastric cardia cancer. J Natl Cancer Inst 1999, 91:747-749.
• [12]Ku GY, Ilson DH: Chemotherapeutic options for gastroesophageal junction tumors. Semin Radiat Oncol 2013, 23:24-30.
• [13]Parfitt JR, Miladinovic Z, Driman DK: Increasing incidence of adenocarcinoma of the gastroesophageal junction and distal stomach in Canada -- an epidemiological study from 1964-2002. Can J Gastroenterol = Journal canadien de gastroenterologie 2006, 20:271-276.
• [14]Ozawa S, Ando N, Kitagawa Y, Kitajima M: [Does incidence of carcinoma of the esophagogastric junction increase?]. Nihon Geka Gakkai zasshi 1998, 99:542-546.
• [15]Marsman WA, Tytgat GN, ten Kate FJ, van Lanschot JJ: Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction. J Surg Oncol 2005, 92:160-168.
• [16]Ronellenfitsch U, Schwarzbach M, Hofheinz R, Kienle P, Kieser M, Slanger TE, Burmeister B, Kelsen D, Niedzwiecki D, Schuhmacher C, et al.: Preoperative chemo (radio) therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer 2013, 49(15):3149-3158. doi:10.1016/j.ejca.2013.05.029
• [17]Cellini F, Ramella S, Ciresa M, Porziella V, Meacci E, Fiore M, Trodella L, D’Angelillo RM: Role of induction therapy in esophageal cancer. Rays 2005, 30:329-333.
• [18]Kleinberg L: Therapy for locally advanced adenocarcinoma of the gastroesophageal junction: optimizing outcome. Semin Radiat Oncol 2013, 23:38-50.
• [19]Amenabar A, Hoppo T, Jobe BA: Surgical management of gastroesophageal junction tumors. Semin Radiat Oncol 2013, 23:16-23.
• [20]Siewert JR, Holscher AH, Becker K, Gossner W: [Cardia cancer: attempt at a therapeutically relevant classification]. Chirurg 1987, 58:25-32.
• [21]Siewert JR, Stein HJ: Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg 1998, 85:1457-1459.
• [22]Rudiger Siewert J, Feith M, Werner M, Stein HJ: Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg 2000, 232:353-361.
• [23]Feith M, Stein HJ, Siewert JR: Adenocarcinoma of the esophagogastric junction: surgical therapy based on 1602 consecutive resected patients. Surg Oncol Clin N Am 2006, 15:751-764.
• [24]Rice TW, Blackstone EH, Rusch VW: 7th edition of the AJCC cancer staging manual: esophagus and esophagogastric junction. Ann Surg Oncol 2010, 17:1721-1724.
• [25]Sobin L, Gospodarowicz M, Wittekind C: TNM classification of malignant tumors. 7th edition. Oxford: Wiley-Blackwell; 2009.
• [26]Gertler R, Stein HJ, Langer R, Nettelmann M, Schuster T, Hoefler H, Siewert JR, Feith M: Long-term outcome of 2920 patients with cancers of the esophagus and esophagogastric junction: evaluation of the New Union Internationale Contre le Cancer/American Joint Cancer Committee staging system. Ann Surg 2011, 253:689-698.
• [27]Isinger-Ekstrand A, Johansson J, Ohlsson M, Francis P, Staaf J, Jonsson M, Borg A, Nilbert M: Genetic profiles of gastroesophageal cancer: combined analysis using expression array and tiling array–comparative genomic hybridization. Cancer Genet Cytogenet 2010, 200:120-126.
• [28]Leers JM, DeMeester SR, Chan N, Ayazi S, Oezcelik A, Abate E, Banki F, Lipham JC, Hagen JA, DeMeester TR: Clinical characteristics, biologic behavior, and survival after esophagectomy are similar for adenocarcinoma of the gastroesophageal junction and the distal esophagus. J Thorac Cardiovasc Surg 2009, 138:594-602.
• [29]Kurokawa Y, Sasako M, Doki Y: Treatment approaches to esophagogastric junction tumors. Digestive surgery 2013, 30:169-173.
• [30]Lee JS, Douglass HO Jr: D2 dissection for gastric cancer. Surg Oncol 1997, 6:215-225.
• [31]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.
• [32]Kodera Y, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T, Kato T, Kito T: Lymph node status assessment for gastric carcinoma: is the number of metastatic lymph nodes really practical as a parameter for N categories in the TNM classification? Tumor node metastasis. J Surg Oncol 1998, 69:15-20.
• [33]Japanese Gastric Cancer A: Japanese classification of gastric carcinoma - 2nd English edition. Gastric Cancer 1998, 1:10-24.
• [34]Xiong HQ, Gunderson LL, Yao J, Ajani JA: Chemoradiation for resectable gastric cancer. Lancet Oncol 2003, 4:498-505.
• [35]Smalley SR, Gunderson L, Tepper J, Martenson JA Jr, Minsky B, Willett C, Rich T: Gastric surgical adjuvant radiotherapy consensus report: rationale and treatment implementation. Int J Radiat Oncol Biol Phys 2002, 52:283-293.
• [36]Cellini F, Valentini V, Pacelli F, D’Ugo D, Mantini G, Balducci M, Gambacorta MA, Nori S: Preoperative radiotherapy in gastric cancer: CTV definition for conformal therapy according to tumor location. Rays 2003, 28:317-329.
• [37]Matzinger O, Gerber E, Bernstein Z, Maingon P, Haustermans K, Bosset JF, Gulyban A, Poortmans P, Collette L, Kuten A: 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.
• [38]Yi Y, Yu J, Li B, Yang F, Huang W, Sun H, Gong H, Zhou T, Lin H: Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume delineation of regional lymph node in patients with gastric carcinoma. Radiother Oncol 2010, 96:223-230.
• [39]Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V: Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 2011, 12:681-692.
• [40]PDQ®: National Cancer Institute: PDQ® esophageal cancer treatment. Bethesda, MD: National Cancer Institute; Date last modified 02/15/2013: Available at: http://cancer.gov/cancertopics/pdq/treatment/esophageal/HealthProfessional webcite
• [41]Stahl M, Budach W, Meyer HJ, Cervantes A, Group EGW: Esophageal cancer: clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010, 21(Suppl 5):v46-v49.
• [42]Arnott SJ, Duncan W, Gignoux M, Girling DJ, Hansen HS, Launois B, Nygaard K, Parmar MK, Roussel A, Spiliopoulos G, et al.: Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal cancer collaborative group). Int J Radiat Oncol Biol Phys 1998, 41:579-583.
• [43]Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996, 335:462-467.
• [44]Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, et al.: Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation therapy oncology group. JAMA 1999, 281:1623-1627.
• [45]Smith TJ, Ryan LM, Douglass HO Jr, Haller DG, Dayal Y, Kirkwood J, Tormey DC, Schutt AJ, Hinson J, Sischy B: Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern cooperative oncology group. Int J Radiat Oncol Biol Phys 1998, 42:269-276.
• [46]Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M: Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001, 19:305-313.
• [47]Fiorica F, Di Bona D, Schepis F, Licata A, Shahied L, Venturi A, Falchi AM, Craxi A, Camma C: Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut 2004, 53:925-930.
• [48]Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, Ackland S, Gotley DC, Joseph D, Millar J, et al.: Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the esophagus: a randomized controlled phase III trial. Lancet Oncol 2005, 6:659-668.
• [49]Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R: 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.
• [50]Van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, et al.: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012, 366:2074-2084.
• [51]Oppedijk V, van der Gaast A, van Lanschot JJ, Van Hagen P, van Os R, van Rij CM, van der Sangen MJ, Beukema JC, Rutten H, Spruit PH, et al.: Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol 2014. [Epub ahead of print]
• [52]Burmeister BH, Thomas JM, Burmeister EA, Walpole ET, Harvey JA, Thomson DB, Barbour AP, Gotley DC, Smithers BM: Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the esophagus? A randomised phase II trial. Eur J Cancer 2011, 47:354-360.
• [53]Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Konigsrainer A, 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.
• [54]Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G, et al.: Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994, 73:2680-2686.
• [55]Rohatgi PR, Swisher SG, Correa AM, Wu TT, Liao Z, Komaki R, Walsh G, Vaporciyan A, Lynch PM, Rice DC, et al.: Failure patterns correlate with the proportion of residual carcinoma after preoperative chemoradiotherapy for carcinoma of the esophagus. Cancer 2005, 104:1349-1355.
• [56]Rohatgi PR, Mansfield PF, Crane CH, Wu TT, Sunder PK, Ross WA, Morris JS, Pisters PW, Feig BW, Gunderson LL, Ajani JA: Surgical pathology stage by American joint commission on cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma. Cancer 2006, 107:1475-1482.
• [57]Fields RC, Strong VE, Gonen M, Goodman KA, Rizk NP, Kelsen DP, Ilson DH, Tang LH, Brennan MF, Coit DG, Shah MA: 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.
• [58]Platz TA, Nurkin SJ, Fong MK, Groman A, Flaherty L, Malhotra U, Levea CM, Yendamuri S, Warren GW, Nava HR, May KS: Neoadjuvant chemoradiotherapy for esophageal/gastroesophageal carcinoma. J Gastrointest Oncol 2013, 4:137-143.
• [59]Bashash M, Shah A, Hislop G, Treml M, Bretherick K, Janoo-Gilani R, Leach S, Le N, Bajdik C, Brooks-Wilson A: Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction. PLoS One 2013, 8:e59157.
• [60]Peters CJ, Rees JR, Hardwick RH, Hardwick JS, Vowler SL, Ong CA, Zhang C, Save V, O’Donovan M, Rassl D, et al.: A 4-gene signature predicts survival of patients with resected adenocarcinoma of the esophagus, junction, and gastric cardia. Gastroenterology 2010, 139:1995-2004. e1915
• [61]Pan JY, Ajani JA, Gu J, Gong Y, Quin A, Hung M, Wu X, Izzo JG: Association of Aurora-A (STK15) kinase polymorphisms with clinical outcome of esophageal cancer treated with preoperative chemoradiation. Cancer 2012, 118:4346-4353.
• [62]Chong IY, Cunningham D, Barber LJ, Campbell J, Chen L, Kozarewa I, Fenwick K, Assiotis I, Guettler S, Garcia-Murillas I, et al.: The genomic landscape of oesophagogastric junctional adenocarcinoma. J Pathol 2013, 231:301-310.
• [63]Chirieac LR, Swisher SG, Correa AM, Ajani JA, Komaki RR, Rashid A, Hamilton SR, Wu TT: Signet-ring cell or mucinous histology after preoperative chemoradiation and survival in patients with esophageal or esophagogastric junction adenocarcinoma. Clin Cancer Res 2005, 11:2229-2236.
• [64]Bekkar S, Gronnier C, Messager M, Robb WB, Piessen G, Mariette C, Group-FRENCH FW: The impact of preoperative radiochemotherapy on survival in advanced esophagogastric junction signet ring cell adenocarcinoma. Ann Thorac Surg 2014, 97:303-310.
• [65]Enlow JM, Denlinger CE, Stroud MR, Ralston JS, Reed CE: Adenocarcinoma of the esophagus with signet ring cell features portends a poor prognosis. Ann Thorac Surg 2013, 96:1927-1932.