Endoscopic ultrasound measurements for detection of residual disease after neoadjuvant chemoradiotherapy for esophageal cancerTRIAL REGISTRATION: Prospective multicenter single-arm diagnostic cohort study NTR4834 at trialregister.nl
submitted 12. Juli 2018
accepted after revision 04. Oktober 2018
29. November 2018 (online)
Background Endoscopic ultrasound (EUS) measurements of residual thickness and residual area have been suggested to correlate with histopathological residual tumor after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study assessed the predictive value of EUS-based measurements using tumor thickness and tumor area before nCRT, and residual thickness and residual area 6 and 12 weeks after completion of nCRT for detection of residual disease.
Methods This was a substudy of the diagnostic multicenter preSANO trial. The primary end point of the current study was the percentage of tumor regression grade (TRG) 3 – 4 (> 10 % vital tumor cells) residual disease that was detected using EUS-based measurements. Associations of absolute measurements of residual thickness/area and proportional change compared with baseline were evaluated. In the case of a statistically significant association, optimal cut-offs to distinguish TRG3 – 4 residual disease from TRG1 (no vital tumor cells) were determined using Youden’s J index.
Results 138 patients were included. Residual thickness and residual area were statistically significantly associated with TRG3 – 4 residual disease 12 weeks after completion of nCRT (odds ratio 1.36, P < 0.01 and 1.64, P = 0.02, respectively). The cut-off for residual thickness was 4.5 mm, which correctly detected 87 % of TRG3 – 4 residual disease and 52 % of TRG1. The cut-off for residual area was 0.92 cm2, which detected 89 % of TRG3 – 4 residual disease and 40 % of TRG1.
Conclusions EUS measurements of residual thickness and residual area adequately detected TRG3 – 4 residual disease with a sensitivity of almost 90 % 12 weeks after completion of nCRT. Hence, residual thickness and residual area may aid in the restaging of esophageal cancer after nCRT.
* These authors contributed equally to this work.
- 1 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
- 2 Shapiro J, van Lanschot JJB, Hulshof M. et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015; 16: 1090-1098
- 3 Verhoef C, van de Weyer R, Schaapveld M. et al. Better survival in patients with esophageal cancer after surgical treatment in university hospitals: a plea for performance by surgical oncologists. Ann Surg Oncol 2007; 14: 1678-1687
- 4 Noordman BJ, Verdam MGE, Lagarde SM. et al. Impact of neoadjuvant chemoradiotherapy on health-related quality of life in long-term survivors of esophageal or junctional cancer: results from the randomized CROSS trial. Ann Oncol 2018; 29: 445-451
- 5 Noordman BJ, Verdam MGE, Lagarde SM. et al. Effect of neoadjuvant chemoradiotherapy on health-related quality of life in esophageal or junctional cancer: results from the randomized CROSS Trial. J Clin Oncol 2018; 36: 268-275
- 6 Noordman BJ, Shapiro J, Spaander MC. et al. Accuracy of detecting residual disease after Cross neoadjuvant chemoradiotherapy for esophageal cancer (preSANO Trial): rationale and protocol. JMIR Res Protoc 2015; 4: e79
- 7 Noordman BJ, Spaander MCW, Valkema R. et al. Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study. Lancet Oncol 2018; 19: 965-974
- 8 Westerterp M, van Westreenen HL, Reitsma JB. et al. Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy – systematic review. Radiology 2005; 236: 841-851
- 9 Puli SR, Reddy JB, Bechtold ML. et al. Staging accuracy of esophageal cancer by endoscopic ultrasound: a meta-analysis and systematic review. World J Gastroenterol 2008; 14: 1479-1490
- 10 van Rossum PS, Goense L, Meziani J. et al. Endoscopic biopsy and EUS for the detection of pathologic complete response after neoadjuvant chemoradiotherapy in esophageal cancer: a systematic review and meta-analysis. Gastrointest Endosc 2016; 83: 866-879
- 11 Sun F, Chen T, Han J. et al. Staging accuracy of endoscopic ultrasound for esophageal cancer after neoadjuvant chemotherapy: a meta-analysis and systematic review. Dis Esophagus 2015; 28: 757-771
- 12 Yen TJ, Chung CS, Wu YW. et al. Comparative study between endoscopic ultrasonography and positron emission tomography-computed tomography in staging patients with esophageal squamous cell carcinoma. Dis Esophagus 2012; 25: 40-47
- 13 Heinzow HS, Seifert H, Tsepetonidis S. et al. Endoscopic ultrasound in staging esophageal cancer after neoadjuvant chemotherapy – results of a multicenter cohort analysis. J Gastrointest Surg 2013; 17: 1050-1057
- 14 Misra S, Choi M, Livingstone AS. et al. The role of endoscopic ultrasound in assessing tumor response and staging after neoadjuvant chemotherapy for esophageal cancer. Surg Endosc 2012; 26: 518-522
- 15 Ribeiro A, Franceschi D, Parra J. et al. Endoscopic ultrasound restaging after neoadjuvant chemotherapy in esophageal cancer. Am J Gastroenterol 2006; 101: 1216-1221
- 16 Jost C, Binek J, Schuller JC. et al. Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02). Gastrointest Endosc 2010; 71: 1114-1121
- 17 Isenberg G, Chak A, Canto MI. et al. Endoscopic ultrasound in restaging of esophageal cancer after neoadjuvant chemoradiation. Gastrointest Endosc 1998; 48: 158-163
- 18 Willis J, Cooper GS, Isenberg G. et al. Correlation of EUS measurement with pathologic assessment of neoadjuvant therapy response in esophageal carcinoma. Gastrointest Endosc 2002; 55: 655-661
- 19 Hirata N, Kawamoto K, Ueyama T. et al. Using endosonography to assess the effects of neoadjuvant therapy in patients with advanced esophageal cancer. AJR Am J Roentgenol 1997; 169: 485-491
- 20 Mesenas S, Vu C, McStay M. et al. A large series, resection controlled study to assess the value of radial EUS in restaging gastroesophageal cancer following neoadjuvant chemotherapy. Dis Esophagus 2008; 21: 37-42
- 21 Chak A, Canto MI, Cooper GS. et al. Endosonographic assessment of multimodality therapy predicts survival of esophageal carcinoma patients. Cancer 2000; 88: 1788-1795
- 22 Bowrey DJ, Clark GW, Roberts SA. et al. Serial endoscopic ultrasound in the assessment of response to chemoradiotherapy for carcinoma of the esophagus. J Gastrointest Surg 1999; 3: 462-467
- 23 Shim CN, Song MK, Lee HS. et al. Prediction of survival by tumor area on endosonography after definitive chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus. Digestion 2014; 90: 98-107
- 24 Chirieac LR, Swisher SG, Ajani JA. et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer 2005; 103: 1347-1355
- 25 Robin X, Turck N, Hainard A. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 2011; 12: 77
- 26 Noordman BJ, Wijnhoven BPL, Lagarde SM. et al. Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial. BMC Cancer 2018; 18: 142