Top

Published in:

Open Access 01-12-2018 | Study protocol

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study

Authors: A. S. Borggreve, S. Mook, M. Verheij, V. E. M. Mul, J. J. Bergman, A. Bartels-Rutten, L. C. ter Beek, R. G. H. Beets-Tan, R. J. Bennink, M. I. van Berge Henegouwen, L. A. A. Brosens, I. L. Defize, J. M. van Dieren, H. Dijkstra, R. van Hillegersberg, M. C. Hulshof, H. W. M. van Laarhoven, M. G. E. H. Lam, A. L. H. M. W. van Lier, C. T. Muijs, W. B. Nagengast, A. J. Nederveen, W. Noordzij, J. T. M. Plukker, P. S. N. van Rossum, J. P. Ruurda, J. W. van Sandick, B. L. A. M. Weusten, F. E. M. Voncken, D. Yakar, G. J. Meijer, on behalf of the PRIDE study group

Published in: BMC Cancer | Issue 1/2018

Abstract

Background

Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and ¹⁸F-fluorodeoxyglucose positron emission tomography with computed tomography (¹⁸F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR.

Methods

The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and ¹⁸F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival.

Discussion

If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped.

Trial registration

The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341.

Fitzmaurice C, Dicker D, Pain A, et al. The global burden of cancer 2013. JAMA Oncol. 2015;1(4):505. https://doi.org/10.1001/jamaoncol.2015.0735.CrossRef

Cunningham D, Allum WWH, Stenning SSP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20. https://doi.org/10.1056/NEJMoa055531.CrossRefPubMed

Ychou M, Boige V, Pignon J, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715.CrossRef

van Hagen P, Hulshof MCCMC, Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84. https://doi.org/10.1056/NEJMoa1112088.CrossRef

Djärv T, Lagergren J, Blazeby JM, Lagergren P. Long-term health-related quality of life following surgery for oesophageal cancer. Br J Surg. 2008;95(9):1121–6. https://doi.org/10.1002/bjs.6293.CrossRefPubMed

Mc Cormack O, Zaborowski A, King S, et al. New-onset atrial fibrillation post-surgery for esophageal and junctional cancer incidence, management, and impact on short-and long-term outcomes. Ann Surg. 2014;260(5):772–8. https://doi.org/10.1097/SLA.0000000000000960.CrossRefPubMed

Kassis ES, Kosinski AS, Ross P, Koppes KE, Donahue JM, Daniel VC. Predictors of anastomotic leak after esophagectomy: an analysis of the society of thoracic surgeons general thoracic database. Ann Thorac Surg. 2013;96(6):1919–26. https://doi.org/10.1016/j.athoracsur.2013.07.119.CrossRefPubMed

Busweiler LAD, Wijnhoven BPL, van Berge Henegouwen MI, et al. Early outcomes from the Dutch upper gastrointestinal cancer audit. Br J Surg. 2016;103(13):1855–63. https://doi.org/10.1002/bjs.10303.CrossRef

Schandl A, Lagergren J, Johar A, Lagergren P. Health-related quality of life 10 years after oesophageal cancer surgery. Eur J Cancer. 2016;69:43–50. https://doi.org/10.1016/J.EJCA.2016.09.032.CrossRefPubMed

10.

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(3):841–51. https://doi.org/10.1148/radiol.2363041042.CrossRef

11.

van Heijl M, Phoa SSKS, van Berge Henegouwen MI, et al. Accuracy and reproducibility of 3D-CT measurements for early response assessment of chemoradiotherapy in patients with oesophageal cancer. Eur J Surg Oncol. 2011;37(12):1064–71. https://doi.org/10.1016/j.ejso.2011.09.004.CrossRefPubMed

12.

Yip C, Cook GJR, Landau DB, Davies A, Goh V. Performance of different imaging modalities in assessment of response to neoadjuvant therapy in primary esophageal cancer. Dis Esophagus. 2016;29(2):116–30. https://doi.org/10.1111/dote.12315.CrossRefPubMed

13.

Ngamruengphong S, Sharma VK, Nguyen B, Das A. Assessment of response to neoadjuvant therapy in esophageal cancer: an updated systematic review of diagnostic accuracy of endoscopic ultrasonography and fluorodeoxyglucose positron emission tomography. Dis Esophagus. 2010;23(3):216–31. https://doi.org/10.1111/j.1442-2050.2009.00989.x.CrossRefPubMed

14.

van Rossum PSN, 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(5):866–79. https://doi.org/10.1016/j.gie.2015.11.026.CrossRefPubMed

15.

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. https://doi.org/10.1016/S1470-2045(18)30201-8.CrossRef

16.

Evelhoch JL, LoRusso PM, He Z, et al. Magnetic resonance imaging measurements of the response of murine and human tumors to the vascular-targeting agent ZD6126. Clin Cancer Res. 2004;10(11):3650–7. https://doi.org/10.1158/1078-0432.CCR-03-0417.CrossRefPubMed

17.

Roedl JB, Halpern EF, Colen RR, Sahani DV, Fischman AJ, Blake MA. Metabolic tumor width parameters as determined on PET/CT predict disease-free survival and treatment response in squamous cell carcinoma of the esophagus. Molecular Imaging and Biology. 2009;11(1):54–60.CrossRef

18.

Heethuis SE, van Rossum PSN, Lips IM, et al. Dynamic contrast-enhanced MRI for treatment response assessment in patients with oesophageal cancer receiving neoadjuvant chemoradiotherapy. Radiother Oncol. 2016;120(1):128–35. https://doi.org/10.1016/j.radonc.2016.05.009.CrossRefPubMed

19.

Kwee RM. Prediction of tumor response to neoadjuvant therapy in patients with esophageal cancer with use of ¹⁸F FDG PET: a systematic review. Radiology. 2010;254(3):707–17. https://doi.org/10.1148/radiol.09091324.CrossRef

20.

Aoyagi T, Shuto K, Okazumi S, Shimada H, Kazama T, Matsubara H. Apparent diffusion coefficient values measured by diffusion-weighted imaging predict chemoradiotherapeutic effect for advanced esophageal cancer. Dig Surg. 2011;28(4):252–7. https://doi.org/10.1159/000328770.CrossRefPubMed

21.

De Cobelli F, Giganti F, Orsenigo E, et al. Apparent diffusion coefficient modifications in assessing gastro-oesophageal cancer response to neoadjuvant treatment: comparison with tumour regression grade at histology. Eur Radiol. 2013;23(8):2165–74. https://doi.org/10.1007/s00330-013-2807-0.CrossRefPubMed

22.

van Rossum PSN, van Lier ALHMW, van Vulpen M, et al. Diffusion-weighted magnetic resonance imaging for the prediction of pathologic response to neoadjuvant chemoradiotherapy in esophageal cancer. Radiother Oncol. 2015;115(2):163–70. https://doi.org/10.1016/j.radonc.2015.04.027.CrossRefPubMed

23.

Wang L, Liu L, Han C, et al. Chemoradiotherapy of esophageal cancer the diffusion-weighted magnetic resonance imaging (DWI) predicts the early response of esophageal squamous cell carcinoma to concurrent chemoradiotherapy. Radiother Oncol. 2016;121:246–51. https://doi.org/10.1016/j.radonc.2016.10.021.CrossRefPubMed

24.

Fang P, Musall BC, Son JB, et al. Multimodal imaging of pathologic response to chemoradiation in esophageal cancer. Int J Radiat Oncol. 2018. https://doi.org/10.1016/j.ijrobp.2018.02.029.CrossRef

25.

Sclafani F, Smyth E, Cunningham D, Chau I, Turner A, Watkins D. A pilot study assessing the incidence and clinical significance of circulating tumor cells in esophagogastric cancers. Clin Colorectal Cancer. 2014;13(2):94–9. https://doi.org/10.1016/j.clcc.2013.11.003.CrossRefPubMed

26.

Reeh M, Effenberger KE, Koenig AM, et al. Circulating tumor cells as a biomarker for preoperative prognostic staging in patients with esophageal cancer. Ann Surg. 2015;261(6):1124–30. https://doi.org/10.1097/SLA.0000000000001130.CrossRef

27.

Gopalan V, Lam AK. Circulatory tumor cells in esophageal adenocarcinoma. Methods Mol Biol. 2018;1756:177–86. https://doi.org/10.1007/978-1-4939-7734-5_16.CrossRefPubMed

28.

Creemers A, Krausz S, Strijker M, et al. Clinical value of ctDNA in upper-GI cancers: a systematic review and meta-analysis. Biochim Biophys Acta. 2017;1868(2):394–403. https://doi.org/10.1016/j.bbcan.2017.08.002.CrossRef

29.

Boellaard R, Delgado-Bolton R, Oyen WJG, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42(2):328–54. https://doi.org/10.1007/s00259-014-2961-x.CrossRefPubMed

30.

Corradetti M, Hatch J, Torok J, et al. Dynamic changes in cell-free DNA during chemoradiation for non–small cell lung cancer. Int J Radiat Oncol. 2017;99(2):S114–5. https://doi.org/10.1016/J.IJROBP.2017.06.270.CrossRef

31.

van Ginkel JH, van den Broek DA, van Kuik J, et al. Preanalytical blood sample workup for cell-free DNA analysis using droplet digital PCR for future molecular cancer diagnostics. Cancer Med. 2017;6(10):2297–307. https://doi.org/10.1002/cam4.1184.CrossRefPubMedPubMedCentral

32.

National guideline esophageal cancer (version 3.1). 2015. http://www.oncoline.nl/oesofaguscarcinoom. Accessed March 21, 2018.

33.

Washington K. 7th edition of the AJCC Cancer staging manual: stomach. Ann Surg Oncol. 2010;17(12):3077–9. https://doi.org/10.1245/s10434-010-1362-z.CrossRefPubMed

34.

Chirieac LR, Swisher SG, Ajani JA, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer. 2005;103(7):1347–55. https://doi.org/10.1002/cncr.20916.CrossRefPubMed

35.

Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73(11):2680–6.CrossRef

36.

Bossuyt PM, Reitsma JB, Bruns DE, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015;351:h5527. https://doi.org/10.1136/BMJ.H5527.CrossRefPubMedPubMedCentral

37.

Collins GS, Reitsma JB, Altman DG, Moons KGM. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMJ. 2015;350:g7594. https://doi.org/10.1016/j.eururo.2014.11.025.CrossRefPubMed

38.

Austin PC, Steyerberg EW. Events per variable (EPV) and the relative performance of different strategies for estimating the out-of-sample validity of logistic regression models. Stat Methods Med Res. 2017;26(2):796–808. https://doi.org/10.1177/0962280214558972.CrossRefPubMed

39.

Peduzzi P, Concato J, Kemper E, Holford T, Feinstein A. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373–9.CrossRef

40.

Taketa T, Correa AM, Suzuki A, et al. Outcome of trimodality-eligible esophagogastric cancer patients who declined surgery after preoperative chemoradiation. Oncology. 2012;83(5):300–4. https://doi.org/10.1159/000341353.CrossRef

41.

Noordman BJ, Wijnhoven BPL, Lagarde SM, et al. Active surveillance in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal or junctional cancer. Dis Esophagus. 2017;30(12):1–8. https://doi.org/10.1093/dote/dox100.CrossRefPubMed

42.

Semenkovich TR, Meyers BF. Surveillance versus esophagectomy in esophageal cancer patients with a clinical complete response after induction chemoradiation. Ann Transl Med. 2018;6(4). https://doi.org/10.21037/18301.

43.

van Heijl M, Omloo JM, van Berge Henegouwen MI, et al. Fluorodeoxyglucose positron emission tomography for evaluating early response during neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer. Ann Surg. 2011;253(1):56–63. https://doi.org/10.1097/SLA.0b013e3181f66596.CrossRef

44.

Wieder HA, Ott K, Lordick F, et al. Prediction of tumor response by FDG-PET: comparison of the accuracy of single and sequential studies in patients with adenocarcinomas of the esophagogastric junction. Eur J Nucl Med Mol Imaging. 2007;34(12):1925–32. https://doi.org/10.1007/s00259-007-0521-3.CrossRefPubMed

45.

Westerterp M, Omloo JMT, Sloof GW, et al. Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET. Int J Hyperth. 2006;22(2):149–60. https://doi.org/10.1080/02656730500513523.CrossRef

46.

van Rossum PSN, Fried DV, Zhang L, et al. The incremental value of subjective and quantitative assessment of 18F-FDG PET for the prediction of pathologic complete response to preoperative chemoradiotherapy in esophageal cancer. J Nucl Med. 2016;57(5):691–700. https://doi.org/10.2967/jnumed.115.163766.CrossRef

47.

Noordman BJ, BPL W, Lagarde SM, et al. Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial. BMC Cancer. 2018;18(1):142. https://doi.org/10.1186/s12885-018-4034-1.CrossRefPubMedPubMedCentral

Title: Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study
Authors: A. S. Borggreve
S. Mook
M. Verheij
V. E. M. Mul
J. J. Bergman
A. Bartels-Rutten
L. C. ter Beek
R. G. H. Beets-Tan
R. J. Bennink
M. I. van Berge Henegouwen
L. A. A. Brosens
I. L. Defize
J. M. van Dieren
H. Dijkstra
R. van Hillegersberg
M. C. Hulshof
H. W. M. van Laarhoven
M. G. E. H. Lam
A. L. H. M. W. van Lier
C. T. Muijs
W. B. Nagengast
A. J. Nederveen
W. Noordzij
J. T. M. Plukker
P. S. N. van Rossum
J. P. Ruurda
J. W. van Sandick
B. L. A. M. Weusten
F. E. M. Voncken
D. Yakar
G. J. Meijer
on behalf of the PRIDE study group
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-4892-6

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2018

ALDH1A3 upregulation and spontaneous metastasis formation is associated with acquired chemoresistance in colorectal cancer cells

Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan

Domain-specific physical activity and the risk of colorectal cancer: results from the Melbourne Collaborative Cohort Study

Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites

A prospective clinical and biological database for pancreatic adenocarcinoma: the BACAP cohort

Androgen deprivation therapy during and after post-prostatectomy radiotherapy in patients with prostate cancer: a case control study

Keynote webinar | Spotlight on antibody–drug conjugates in cancer