Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

Open Access 01-01-2017 | Original Article

The value of ¹⁸F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

Authors: Peter S. N. van Rossum, David V. Fried, Lifei Zhang, Wayne L. Hofstetter, Linus Ho, Gert J. Meijer, Brett W. Carter, Laurence E. Court, Steven H. Lin

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2017

Abstract

Purpose

The purpose of our study was to determine the value of ¹⁸F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT).

Methods

In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, ¹⁸F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV_max, SUV_mean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed.

Results

A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of −26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18).

Conclusions

¹⁸F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early ¹⁸F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders.

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012. doi:10.1056/NEJMoa1112088.PubMed

Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009. doi:10.1200/JCO.2009.22.2083.PubMed

Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011. doi:10.1016/S1470-2045(11)70142-5.PubMed

Teniere P, Hay JM, Fingerhut A, Fagniez PL. Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. Surg Gynecol Obstet 1991.

Zieren HU, Muller JM, Jacobi CA, Pichlmaier H, Muller RP, Staar S. Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: a prospective randomized study. World J Surg 1995.

Pouliquen X, Levard H, Hay JM, McGee K, Fingerhut A, Langlois-Zantin O. 5-Fluorouracil and cisplatin therapy after palliative surgical resection of squamous cell carcinoma of the esophagus. A multicenter randomized trial. French Associations for Surgical Research. Ann Surg 1996.

Ando N, Iizuka T, Kakegawa T, Isono K, Watanabe H, Ide H, Tanaka O, Shinoda M, Takiyama W, Arimori M, Ishida K, Tsugane S. A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study. J Thorac Cardiovasc Surg 1997.

Shapiro J, van Lanschot JJ, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, Ten Kate FJ, Creemers GM, Punt CJ, Plukker JT, Verheul HM, Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A, CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015.

Oppedijk V, van der Gaast A, van Lanschot JJ, van Hagen P, van Os R, van Rij CM, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014. doi:10.1200/JCO.2013.51.2186.

10.

Ajani JA, Komaki R, Putnam JB, Walsh G, Nesbitt J, Pisters PW, Lynch PM, Vaporciyan A, Smythe R, Lahoti S, Raijman I, Swisher S, Martin FD, Roth JA. A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction. Cancer 2001.

11.

Bains MS, Stojadinovic A, Minsky B, Rusch V, Turnbull A, Korst R, Ginsberg R, Kelsen DP, Ilson DH. A phase II trial of preoperative combined-modality therapy for localized esophageal carcinoma: initial results. J Thorac Cardiovasc Surg 2002.

12.

Ilson DH, Bains M, Kelsen DP, O’Reilly E, Karpeh M, Coit D, et al. Phase I trial of escalating-dose irinotecan given weekly with cisplatin and concurrent radiotherapy in locally advanced esophageal cancer. J Clin Oncol. 2003. doi:10.1200/JCO.2003.02.147.

13.

Swisher SG, Ajani JA, Komaki R, Nesbitt JC, Correa AM, Cox JD, Lahoti S, Martin F, Putnam JB, Smythe WR, Vaporciyan AA, Walsh GL, Roth JA. Long-term outcome of phase II trial evaluating chemotherapy, chemoradiotherapy, and surgery for locoregionally advanced esophageal cancer. Int J Radiat Oncol Biol Phys 2003.

14.

Ajani JA, Walsh G, Komaki R, Morris J, Swisher SG, Putnam Jr JB, et al. Preoperative induction of CPT-11 and cisplatin chemotherapy followed by chemoradiotherapy in patients with locoregional carcinoma of the esophagus or gastroesophageal junction. Cancer. 2004. doi:10.1002/cncr.20284.

15.

Jin J, Liao Z, Zhang Z, Ajani J, Swisher S, Chang JY, et al. Induction chemotherapy improved outcomes of patients with resectable esophageal cancer who received chemoradiotherapy followed by surgery. Int J Radiat Oncol Biol Phys. 2004. doi:10.1016/j.ijrobp.2004.03.033.

16.

Malaisrie SC, Hofstetter WL, Correa AM, Ajani JA, Komaki RR, Rice DC, et al. The addition of induction chemotherapy to preoperative, concurrent chemoradiotherapy improves tumor response in patients with esophageal adenocarcinoma. Cancer. 2006. doi:10.1002/cncr.22077.PubMed

17.

Javeri H, Arora R, Correa AM, Hofstetter WL, Lee JH, Liao Z, et al. Influence of induction chemotherapy and class of cytotoxics on pathologic response and survival after preoperative chemoradiation in patients with carcinoma of the esophagus. Cancer. 2008. doi:10.1002/cncr.23688.PubMed

18.

Ribi K, Koeberle D, Schuller JC, Honegger H, Roth A, Hess V, et al. Is a change in patient-reported dysphagia after induction chemotherapy in locally advanced esophageal cancer a predictive factor for pathological response to neoadjuvant chemoradiation? Support Care Cancer. 2009. doi:10.1007/s00520-008-0570-6.PubMed

19.

Ruhstaller T, Widmer L, Schuller JC, Roth A, Hess V, Mingrone W, et al. Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02). Ann Oncol. 2009. doi:10.1093/annonc/mdp045.PubMed

20.

Sergeant G, Deroose C, De Hertogh G, Moons J, Coosemans W, Nafteux P, et al. Early metabolic response evaluation on PET-CT after a single cycle of chemotherapy in patients with cT3-4N0/+ oesophageal or GE-junction cancer subsequently treated by neoadjuvant chemoradiotherapy. J Clin Oncol. 2010;28:e14505 (Meeting Abstracts).

21.

Choong NW, Mauer AM, Haraf DC, Ferguson MK, Sandler AB, Kesler KA, et al. Long-term outcome of a phase II study of docetaxel-based multimodality chemoradiotherapy for locally advanced carcinoma of the esophagus or gastroesophageal junction. Med Oncol. 2011. doi:10.1007/s12032-010-9658-1.PubMed

22.

De Vita F, Orditura M, Martinelli E, Vecchione L, Innocenti R, Sileni VC, et al. A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer. Br J Cancer. 2011. doi:10.1038/sj.bjc.6606093.PubMedPubMedCentral

23.

Eisterer W, DE Vries A, Kendler D, Spechtenhauser B, Konigsrainer A, Nehoda H, Virgolini I, Lukas P, Bechter O, Woll E, Ofner D. Triple induction chemotherapy and chemoradiotherapy for locally advanced esophageal cancer. A phase II study. Anticancer Res 2011.

24.

Ilson DH, Minsky BD, Ku GY, Rusch V, Rizk N, Shah M, et al. Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer. Cancer. 2012. doi:10.1002/cncr.26591.

25.

Koo DH, Park SI, Kim YH, Kim JH, Jung HY, Lee GH, et al. Phase II study of use of a single cycle of induction chemotherapy and concurrent chemoradiotherapy containing capecitabine/cisplatin followed by surgery for patients with resectable esophageal squamous cell carcinoma: long-term follow-up data. Cancer Chemother Pharmacol. 2012. doi:10.1007/s00280-011-1750-5.

26.

Ishihara R, Yamamoto S, Iishi H, Nagai K, Matui F, Kawada N, et al. Predicting the effects of chemoradiotherapy for squamous cell carcinoma of the esophagus by induction chemotherapy response assessed by positron emission tomography: toward PET-response-guided selection of chemoradiotherapy or esophagectomy. Int J Clin Oncol. 2012. doi:10.1007/s10147-011-0278-3.PubMed

27.

Ajani JA, Xiao L, Roth JA, Hofstetter WL, Walsh G, Komaki R, et al. A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann Oncol. 2013. doi:10.1093/annonc/mdt339.PubMedCentral

28.

Alberts SR, Soori GS, Shi Q, Wigle DA, Sticca RP, Miller RC, Leenstra JL, Peller PJ, Wu T-, Yoon HH, Drevyanko TF, Ko S, Mattar BI, Nikcevich DA, Behrens RJ, Khalil MF, Kim GP. Randomized phase II trial of extended versus standard neoadjuvant therapy for esophageal cancer, NCCTG (Alliance) trial N0849. J Clin Oncol 2013.

29.

Yoon DH, Jang G, Kim JH, Kim YH, Kim JY, Kim HR, et al. Randomized phase 2 trial of S1 and oxaliplatin-based chemoradiotherapy with or without induction chemotherapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2015. doi:10.1016/j.ijrobp.2014.11.019.

30.

Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005. doi:10.1200/JCO.2005.00.034.

31.

Holscher AH, Bollschweiler E, Bogoevski D, Schmidt H, Semrau R, Izbicki JR. Prognostic impact of neoadjuvant chemoradiation in cT3 oesophageal cancer - A propensity score matched analysis. Eur J Cancer. 2014. doi:10.1016/j.ejca.2014.08.020.PubMed

32.

Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007. doi:10.1016/S1470-2045(07)70244-9.PubMed

33.

van Rossum PS, van Lier AL, Lips IM, Meijer GJ, Reerink O, van Vulpen M, et al. Imaging of oesophageal cancer with FDG-PET/CT and MRI. Clin Radiol. 2015. doi:10.1016/j.crad.2014.07.017.PubMed

34.

Bruzzi JF, Swisher SG, Truong MT, Munden RF, Hofstetter WL, Macapinlac HA, et al. Detection of interval distant metastases: clinical utility of integrated CT-PET imaging in patients with esophageal carcinoma after neoadjuvant therapy. Cancer. 2007. doi:10.1002/cncr.22397.PubMed

35.

Stiekema J, Vermeulen D, Vegt E, Voncken FE, Aleman BM, Sanders J, et al. Detecting interval metastases and response assessment using 18F-FDG PET/CT after neoadjuvant chemoradiotherapy for esophageal cancer. Clin Nucl Med. 2014. doi:10.1097/RLU.0000000000000517.PubMed

36.

Blom RL, Schreurs WM, Belgers HJ, Oostenbrug LE, Vliegen RF, Sosef MN. The value of post-neoadjuvant therapy PET-CT in the detection of interval metastases in esophageal carcinoma. Eur J Surg Oncol. 2011. doi:10.1016/j.ejso.2011.06.002.PubMed

37.

Elliott JA, O’Farrell NJ, King S, Halpenny D, Malik V, Muldoon C, et al. Value of CT-PET after neoadjuvant chemoradiation in the prediction of histological tumour regression, nodal status and survival in oesophageal adenocarcinoma. Br J Surg. 2014. doi:10.1002/bjs.9670.

38.

Westerterp M, van Westreenen HL, Reitsma JB, Hoekstra OS, Stoker J, Fockens P, et al. Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy--systematic review. Radiology. 2005. doi:10.1148/radiol.2363041042.PubMed

39.

Wieder HA, Beer AJ, Lordick F, Ott K, Fischer M, Rummeny EJ, Ziegler S, Siewer JR, Schwaiger M, Weber WA. Comparison of changes in tumor metabolic activity and tumor size during chemotherapy of adenocarcinomas of the esophagogastric junction. J Nucl Med 2005.

40.

Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC, Standards for Reporting of Diagnostic Accuracy. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 2003.

41.

Edge S, Byrd D, Compton C. AJCC cancer staging manual; 2010. pp. 103–15.

42.

Chirieac LR, Swisher SG, Ajani JA, Komaki RR, Correa AM, Morris JS, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer. 2005. doi:10.1002/cncr.20916.PubMed

43.

Werner-Wasik M, Nelson AD, Choi W, Arai Y, Faulhaber PF, Kang P, et al. What is the best way to contour lung tumors on PET scans? Multiobserver validation of a gradient-based method using a NSCLC digital PET phantom. Int J Radiat Oncol Biol Phys. 2012. doi:10.1016/j.ijrobp.2010.12.055.

44.

Roedl JB, Colen RR, Holalkere NS, Fischman AJ, Choi NC, Blake MA. Adenocarcinomas of the esophagus: response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT. Comparison to histopathologic and clinical response evaluation. Radiother Oncol. 2008. doi:10.1016/j.radonc.2008.06.014.PubMed

45.

Weber WA, Ott K, Becker K, Dittler HJ, Helmberger H, Avril NE, Meisetschlager G, Busch R, Siewert JR, Schwaiger M, Fink U. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 2001.

46.

Ott K, Weber WA, Lordick F, Becker K, Busch R, Herrmann K, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2006. doi:10.1200/JCO.2006.06.7801.

47.

Klaeser B, Nitzsche E, Schuller JC, Koberle D, Widmer L, Balmer-Majno S, et al. Limited predictive value of FDG-PET for response assessment in the preoperative treatment of esophageal cancer: results of a prospective multi-center trial (SAKK 75/02). Onkologie. 2009. doi:10.1159/000251842.PubMed

48.

van Rossum PS, Goense L, Meziani J, Reitsma JB, Siersema PD, Vleggaar FP, van Vulpen M, Meijer GJ, Ruurda JP, van Hillegersberg R. 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 2015.

49.

van Rossum PS, van Lier AL, van Vulpen M, Reerink O, Lagendijk JJ, Lin SH, et al. Diffusion-weighted magnetic resonance imaging for the prediction of pathologic response to neoadjuvant chemoradiotherapy in esophageal cancer. Radiother Oncol. 2015. doi:10.1016/j.radonc.2015.04.027.PubMed

Title: The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma
Authors: Peter S. N. van Rossum
David V. Fried
Lifei Zhang
Wayne L. Hofstetter
Linus Ho
Gert J. Meijer
Brett W. Carter
Laurence E. Court
Steven H. Lin
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2017
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-016-3478-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The value of ¹⁸F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Evaluation of bone-seeking novel radiotracer 68Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast

Prognostic impact of tumour burden assessed by metabolic tumour volume on FDG PET/CT in anal canal cancer

177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

Erratum to: Performance of cardiac cadmium-zinc-telluride gamma camera imaging in coronary artery disease: a review from the cardiovascular committee of the European Association of Nuclear Medicine (EANM)

Metabolic and morphological measurements of subcutaneous and visceral fat and their relationship with disease stage and overall survival in newly diagnosed pancreatic adenocarcinoma

A rare case of rectal carcinoma and prostate carcinoma with coexistent Paget’s disease mimicking bone metastases in both 18F-FDG and 68Ga PSMA PET/CT