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Published in: Radiation Oncology 1/2019

Open Access 01-12-2019 | Endoscopy | Research

Microscopic tumor spread beyond (echo)endoscopically determined tumor borders in esophageal cancer

Authors: Melanie Machiels, Maurits L. van Montfoort, Nikki B. Thuijs, Mark I. van Berge Henegouwen, Tanja Alderliesten, Sybren L. Meijer, Jeanin E. van Hooft, Maarten C. C. M. Hulshof

Published in: Radiation Oncology | Issue 1/2019

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Abstract

Objective

The microscopic tumor spread (MS) beyond the macroscopic tumor borders of esophageal tumors is crucial for determining the clinical target volume (CTV) in radiotherapy. The question arises whether current voluminous CTV margins of 3–5 cm around the macroscopic gross tumor volume (GTV) to account for MS are still accurate when fiducial markers are used for GTV determination. We aimed to pathologically validate the use of fiducial markers placed on the (echo)endoscopically determined tumor border (EDTB) as a surrogate for macroscopic tumor borders and to analyse the MS beyond EDTBs.

Methods

Thirty-three consecutive esophageal cancer patients treated with neo-adjuvant chemoradiotherapy after (echo)endoscopic fiducial marker implantation at cranial and caudal EDTB were included in this study. Fiducial marker positions were detected in the surgical specimens under CT guidance and demarcated with beads, and subsequently analysed for macroscopic tumor spread and MS beyond the demarcations. A logistic regression analysis was performed to determine predicting factors for MS beyond EDTB.

Results

A total of 60 EDTBs were examined in 32 patients. In 50% of patients no or only partial regression of tumor in response to therapy (≥Mandard 3) or higher was seen (i.e., residual tumor group) and included for MS analysis. None had macroscopic tumor spread beyond EDTBs. In the residual tumor group, only 20 and 21% of the cranial and caudal EDTBs were crossed with a maximum of 9 mm and 16 mm MS, respectively. This MS was corrected for each individual determined contraction rate (mean: 93%). Presence of MS beyond EDTB was significantly associated with initial tumor length (p = 0.028).

Conclusion

Our results validate the use of fiducial markers on EDTB as a surrogate for macroscopic tumor and indicate that CTV margins around the GTV to compensate for MS along the esophageal wall can be limited to 1–1.5 cm, when the GTV is determined with fiducial markers.
Literature
1.
go back to reference Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.CrossRef Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.CrossRef
2.
go back to reference Gwynne S, Hurt C, Evans M, et al. Definitive chemoradiation for oesophageal cancer – a standard of care in patients with non-metastatic oesophageal cancer. Clin Oncol (R Coll Radiol). 2011;23:182–8.CrossRef Gwynne S, Hurt C, Evans M, et al. Definitive chemoradiation for oesophageal cancer – a standard of care in patients with non-metastatic oesophageal cancer. Clin Oncol (R Coll Radiol). 2011;23:182–8.CrossRef
3.
go back to reference Nowee ME, Voncken FE, Kotte AN, et al. Interobserver variation of CT and FDG-PET based GTV for oesophageal cancer: a Dutch nationwide study. Radiother Oncol. 2016;119:S330–1.CrossRef Nowee ME, Voncken FE, Kotte AN, et al. Interobserver variation of CT and FDG-PET based GTV for oesophageal cancer: a Dutch nationwide study. Radiother Oncol. 2016;119:S330–1.CrossRef
4.
go back to reference Machiels M, Jin P, Jelvehgaran P, et al. PO-0697: reduced inter- and intra-observer variation in esophageal tumor delineation using fiducial markers. Radiother Oncol. 2017;123:S364–5.CrossRef Machiels M, Jin P, Jelvehgaran P, et al. PO-0697: reduced inter- and intra-observer variation in esophageal tumor delineation using fiducial markers. Radiother Oncol. 2017;123:S364–5.CrossRef
5.
go back to reference van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol. 2004;14:52–64.CrossRef van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol. 2004;14:52–64.CrossRef
6.
go back to reference Jin P, Machiels M, Crama KF, et al. Dosimetric benefits of mid-position compared with internal target volume strategy for esophageal cancer radiation therapy. Int J Radiat Oncol. 2019;103:491–502.CrossRef Jin P, Machiels M, Crama KF, et al. Dosimetric benefits of mid-position compared with internal target volume strategy for esophageal cancer radiation therapy. Int J Radiat Oncol. 2019;103:491–502.CrossRef
7.
go back to reference Gao X-S, Xueying Q, Wu F, et al. Pathological analysis of clinical target volume maring for radiotherapy in patients with esophageal and gastroesophageal junction carcinoma. Int J Radiat Oncol Biol Phys. 2007;67:389–96.CrossRef Gao X-S, Xueying Q, Wu F, et al. Pathological analysis of clinical target volume maring for radiotherapy in patients with esophageal and gastroesophageal junction carcinoma. Int J Radiat Oncol Biol Phys. 2007;67:389–96.CrossRef
8.
go back to reference Lam KY, Ma LT, Wong J. Measurement of extent of spread of oesophageal squamous carcinoma by serial sectioning. J Clin Pathol. 1999;49:124–9.CrossRef Lam KY, Ma LT, Wong J. Measurement of extent of spread of oesophageal squamous carcinoma by serial sectioning. J Clin Pathol. 1999;49:124–9.CrossRef
9.
go back to reference Song Y, Liang Y, Zang R, et al. Application of serial section method to determine the radiotherapy target volume for esophageal squamous carcinoma. Cell Biochem Biophys. 2013;66:351–6.CrossRef Song Y, Liang Y, Zang R, et al. Application of serial section method to determine the radiotherapy target volume for esophageal squamous carcinoma. Cell Biochem Biophys. 2013;66:351–6.CrossRef
10.
go back to reference Machiels M, van Hooft J, Jin P, et al. Endoscopy/EUS-guided fiducial marker placement in patients with esophageal cancer: a comparative analysis of 3 types of markers. Gastrointest Endosc. 2015;82:641–9.CrossRef Machiels M, van Hooft J, Jin P, et al. Endoscopy/EUS-guided fiducial marker placement in patients with esophageal cancer: a comparative analysis of 3 types of markers. Gastrointest Endosc. 2015;82:641–9.CrossRef
11.
go back to reference van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative Chemoradiotherapy for esophageal or Junctional Cancer. N Engl J Med. 2012;366:2074–84.CrossRef van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative Chemoradiotherapy for esophageal or Junctional Cancer. N Engl J Med. 2012;366:2074–84.CrossRef
12.
go back to reference Van Meerten E, Van Der Gaast A, Tilanus HW, et al. Pathological analysis after neoadjuvant chemoradiotherapy for esophageal carcinoma: the Rotterdam experience. J Surg Oncol. 2009;100:32–7.CrossRef Van Meerten E, Van Der Gaast A, Tilanus HW, et al. Pathological analysis after neoadjuvant chemoradiotherapy for esophageal carcinoma: the Rotterdam experience. J Surg Oncol. 2009;100:32–7.CrossRef
13.
go back to reference Mandard A, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6.CrossRef Mandard A, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6.CrossRef
14.
go back to reference Tsutsui S, Kuwano H, Watanabe M, et al. Resection margin for squamous cell carcinoma of the esophagus. Ann Surg. 1995;222:193–202.CrossRef Tsutsui S, Kuwano H, Watanabe M, et al. Resection margin for squamous cell carcinoma of the esophagus. Ann Surg. 1995;222:193–202.CrossRef
15.
go back to reference Siu KF, Cheung HC, Wong J. Shrinkage of the esophagus after resection for carcinoma. Ann Surg. 1985;203:173–6.CrossRef Siu KF, Cheung HC, Wong J. Shrinkage of the esophagus after resection for carcinoma. Ann Surg. 1985;203:173–6.CrossRef
16.
go back to reference Gaur P, Sepesi B, Hofstetter WL, et al. Endoscopic esophageal tumor length: a prognostic factor for patients with esophageal cancer. Cancer. 2011;117:63–9.CrossRef Gaur P, Sepesi B, Hofstetter WL, et al. Endoscopic esophageal tumor length: a prognostic factor for patients with esophageal cancer. Cancer. 2011;117:63–9.CrossRef
17.
go back to reference Wang B, Liu C, Lin C, et al. Endoscopic tumor length is an independent prognostic factor in esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19:2149–58.CrossRef Wang B, Liu C, Lin C, et al. Endoscopic tumor length is an independent prognostic factor in esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19:2149–58.CrossRef
18.
go back to reference Reddymasu SC, Oropeza-Vail M, Pakseresht K, et al. Are endoscopic ultrasonography imaging characteristics reliable for the diagnosis of small upper gastrointestinal subepithelial lesions? J Clin Gastroenterol. 2012;46:42–5.CrossRef Reddymasu SC, Oropeza-Vail M, Pakseresht K, et al. Are endoscopic ultrasonography imaging characteristics reliable for the diagnosis of small upper gastrointestinal subepithelial lesions? J Clin Gastroenterol. 2012;46:42–5.CrossRef
19.
go back to reference Muijs C, Smit J, Karrenbeld A, et al. Residual tumor after Neoadjuvant Chemoradiation outside the radiation therapy target volume: a new prognostic factor for survival in esophageal Cancer. Int J Radiat Oncol. 2014;88:845–52.CrossRef Muijs C, Smit J, Karrenbeld A, et al. Residual tumor after Neoadjuvant Chemoradiation outside the radiation therapy target volume: a new prognostic factor for survival in esophageal Cancer. Int J Radiat Oncol. 2014;88:845–52.CrossRef
20.
go back to reference Matzinger O, Gerber E, Bernstein Z, et al. EORTC-ROG expert opinion: radiotherapy volume and treatment guidelines for neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction and the stomach. Radiother Oncol. 2009;92:164–75.CrossRef Matzinger O, Gerber E, Bernstein Z, et al. EORTC-ROG expert opinion: radiotherapy volume and treatment guidelines for neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction and the stomach. Radiother Oncol. 2009;92:164–75.CrossRef
21.
go back to reference Oppedijk V, van der Gaast A, van Lanschot JJB, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014;32:385–91.CrossRef Oppedijk V, van der Gaast A, van Lanschot JJB, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014;32:385–91.CrossRef
22.
go back to reference Versteijne E, van Laarhoven HWM, van Hooft JE, et al. Definitive chemoradiation for patients with inoperable and/or unresectable esophageal cancer: Locoregional recurrence pattern. Dis Esophagus. 2015;28:453-9.CrossRef Versteijne E, van Laarhoven HWM, van Hooft JE, et al. Definitive chemoradiation for patients with inoperable and/or unresectable esophageal cancer: Locoregional recurrence pattern. Dis Esophagus. 2015;28:453-9.CrossRef
Metadata
Title
Microscopic tumor spread beyond (echo)endoscopically determined tumor borders in esophageal cancer
Authors
Melanie Machiels
Maurits L. van Montfoort
Nikki B. Thuijs
Mark I. van Berge Henegouwen
Tanja Alderliesten
Sybren L. Meijer
Jeanin E. van Hooft
Maarten C. C. M. Hulshof
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2019
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-019-1419-5

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