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Diagnostic Applications of Nuclear Medicine: Esophageal Cancers

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Nuclear Oncology

Abstract

Esophageal cancer is the eighth most commonly diagnosed malignancy worldwide. This chapter will review the epidemiology, environmental factors, genetic predisposition, and underlying biomolecular changes of the disease. The staging of esophageal cancer will be reviewed as well as the roles of conventional diagnostic imaging and nuclear imaging in this staging. Finally, the efficacy of these modalities in assessing response to the various treatments described in the chapter and in the long-term surveillance for disease recurrence will be addressed.

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Abbreviations

AJCC:

American Joint Committee on Cancer

APC:

Gene encoding for adenomatous colon polyposis

c-myc:

Gene encoding for a transcription factor (a multifunctional, nuclear phosphoprotein involved in cell cycle progression, apoptosis, and cellular transformation)

CT:

X-ray computed tomography

erb B-2:

Gene encoding for the receptor tyrosine-protein kinase erbB-2 (also known as CD340 or proto-oncogene Neu)

EUS:

Endoscopic ultrasonography

FAPI:

Fibroblast-activation protein inhibitor

[68Ga]-FAPI:

Gallium-68-conjugated fibroblast-activation protein inhibitor

[18F]FDG:

2-Deoxy-2-[18F]fluoro-d-glucose

GERD:

Gastrointestinal reflux disease

GI:

Gastrointestinal

Gy:

Gray unit (ionizing radiation dose in the International System of Units, corresponding to the absorption of one joule of radiation energy per kilogram of matter)

HPV:

Human papillomavirus

M:

Metastasis status according to the AJCC/UICC TNM staging system

MBq:

Mega-Becquerel (106 Becquerel)

MIP:

Maximum intensity projection

MR:

Magnetic resonance

N:

Lymph node status according to the AJCC/UICC TNM staging system

p16:

Protein encoded by the CDKN2A gene (also known as cyclin-dependent kinase inhibitor 2A or multiple tumor suppressor 1)

p53:

Tumor protein p53, also known as cellular tumor antigen p53, phosphoprotein p53, tumor suppressor p53, antigen NY-CO-13, or transformation-related protein 53 (TRP53)

PERCIST:

Positron emission tomography response criteria in solid tumors

PET:

Positron emission tomography

PET/CT:

Positron emission tomography/computed tomography

PET/MR:

Positron emission tomography/magnetic resonance

Rb:

Gene encoding for the retinoblastoma protein

RECIST:

Response evaluation criteria in solid tumors

SSC:

Squamous cell carcinoma

SUR:

Standardized uptake ratio (ratio of tumor SUV and blood pool SUV)

SUV:

Standardized uptake value

SUVmax:

Standardized uptake value at point of maximum

T:

Tumor status according to the AJCC/UICC TNM staging system

UICC:

Union Internationale Contre le Cancer (International Union Against Cancer)

US:

Ultrasonography

References

  1. Siegel RL, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.

    Article  PubMed  Google Scholar 

  2. Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2020;40(4):313.

    Google Scholar 

  3. Patel N, Benipal B. Incidence of esophageal cancer in the United States from 2001–2015: A United States cancer statistics analysis of 50 States. Cureus. 2018;10(12):e3709.

    PubMed  PubMed Central  Google Scholar 

  4. Lagergren J. Adenocarcinoma of oesophagus: what exactly is the size of the problem and who is at risk? Gut. 2005;54(Suppl 1):i1–5.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gholipour C, Shalchi RA, Abbasi M. A histopathological study of esophageal cancer on the western side of the Caspian littoral from 1994 to 2003. Dis Esophagus. 2008;21(4):322.

    Article  CAS  PubMed  Google Scholar 

  6. Shuyama K, et al. Human papillomavirus in high- and low-risk areas of oesophageal squamous cell carcinoma in China. Br J Cancer. 2007;96(10):1554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Engel LS, et al. Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst. 2003;95(18):1404.

    Article  PubMed  Google Scholar 

  8. Raman R, et al. Changing incidence of esophageal cancer among white women: analysis of SEER data (1992–2010). Contemp Oncol (Pozn). 2015;19(4):338–40.

    PubMed Central  Google Scholar 

  9. Chen T, et al. Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma. Sci Rep. 2015;5:16038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chak A, et al. Familial aggregation of Barrett’s oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults. Gut. 2002;51(3):323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349(23):2241–52.

    Article  CAS  PubMed  Google Scholar 

  12. Lanuti M, et al. A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. Clin Cancer Res. 2008;14(10):3216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kuwano H, et al. Genetic alterations in esophageal cancer. Surg Today. 2005;35(1):7–18.

    Article  PubMed  Google Scholar 

  14. Paulson T, et al. Somatic whole genome dynamics of precancer in Barrett’s Esophagus. Research Square. 2021. https://doi.org/10.21203/rs.3.rs-257949/v1.

  15. Ococks E, et al. Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling. Ann Oncol. 2021;32(4):431–3.

    Article  CAS  Google Scholar 

  16. Kawakami K, et al. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst. 2000;92:1805–11.

    Article  CAS  PubMed  Google Scholar 

  17. Gowryshankar A, Nagaraja V, Eslick GD. HER2 status in Barrett’s esophagus and esophageal cancer: a meta analysis. J Gastrointest Oncol. 2014;5(1):25–35.

    PubMed  PubMed Central  Google Scholar 

  18. Yang YM, et al. Advances in targeted therapy for esophageal cancer. Sig Transduct Target Ther. 2020;5:229.

    Article  CAS  Google Scholar 

  19. Amin MB, et al. AJCC cancer staging manual. 8th ed. Springer; 2017.

    Book  Google Scholar 

  20. D’Journo XB. Clinical implication of the innovations of the 8th edition of the TNM classification for esophageal and esophago-gastric cancer. J Thorac Dis. 2018;10(Suppl 22):S2671–81.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Jimenez-Lillo J, et al. Performance of indocyanine-green imaging for sentinel lymph node mapping and lymph node metastasis in esophageal cancer: systematic review and meta-analysis. Ann Surg Oncol. 2021;28:4868–77.

    Google Scholar 

  22. Ozawa H, et al. Prognostic significance of the number and extent of metastatic lymph nodes in patients with esophageal cancer: comparison of the UICC 8th and JES 11th classification for esophageal cancer. Ann Surg Oncol. 2021;28:6355–63.

    Google Scholar 

  23. Yoon YC, et al. Metastasis to regional lymph nodes in patients with esophageal squamous cell carcinoma: CT versus FDG PET for presurgical detection prospective study. Radiology. 2003;227:764–70.

    Article  PubMed  Google Scholar 

  24. Thakkar S, Kaul V. Endoscopic ultrasound of esophageal cancer. Gastroenterol Hepatol. 2020;16(1):14–20.

    Google Scholar 

  25. Barber TW, et al. 18F-FDG PET/CT has a high impact on patient management and provides powerful prognostic stratification in the primary staging of esophageal cancer: a prospective study with mature survival data. J Nucl Med. 2012;53(6):864–71.

    Google Scholar 

  26. Kato H, et al. The incremental effect of positron emission tomography on diagnostic accuracy in the initial staging of esophageal carcinoma. Cancer. 2005;103(1):148–56.

    Article  PubMed  Google Scholar 

  27. van Vliet EP, et al. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer. 2008;98(3):547.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Manabe O, et al. Diagnostic accuracy of lymph node metastasis depends on metabolic activity of the primary lesion in thoracic squamous esophageal cancer. J Nucl Med. 2013;54(5):670–6.

    Article  CAS  PubMed  Google Scholar 

  29. Chatterton BE, et al. Positron emission tomography changes management and prognostic stratification in patients with oesophageal cancer: results of a multicentre prospective study. Eur J Nucl Med Mol Imaging. 2009;36(3):354–61.

    Article  CAS  PubMed  Google Scholar 

  30. Wallace MB, et al. An analysis of multiple staging management strategies for carcinoma of the esophagus: computed tomography, endoscopic ultrasound, positron emission tomography, and thoracoscopy/laparoscopy. Ann Thorac Surg. 2002;74(4):1026–32.

    Article  PubMed  Google Scholar 

  31. Reinert CP, et al. Impact of PET/CT on management of patients with esophageal cancer – results from a PET/CT registry study. Eur J Radiol. 2021;136:109524.

    Article  PubMed  Google Scholar 

  32. Yasuda T, et al. The impact of F-18 FDG PET positive lymph nodes on postoperative recurrence and survival in resectable thoracic esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19:652–60.

    Article  PubMed  Google Scholar 

  33. Bütof R, et al. Prognostic value of pretherapeutic tumor-to-blood standardized uptake ratio in patients with esophageal carcinoma. J Nucl Med. 2015;56(8):1150–6.

    Article  PubMed  Google Scholar 

  34. Li Y, et al. A FDG-PET radiomics signature detects esophageal squamous cell carcinoma patients who do not benefit from chemoradiation. Sci Rep. 2020;10:17671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lee G, et al. Clinical implication of PET/MR imaging in preoperative esophageal cancer staging: comparison with PET/CT, endoscopic ultrasonography, and CT. J Nucl Med. 2014;55(8):1242–7.

    Article  PubMed  Google Scholar 

  36. Hicks R et al. FAPI PET/CT: will It end the hegemony of 18F-FDG in oncology? J Nucl Med. 2021;62:296–302.

    Google Scholar 

  37. Kratochwil C et al. 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60:801–805.

    Google Scholar 

  38. Gebski V, et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8:226–34.

    Article  CAS  PubMed  Google Scholar 

  39. Rishi A, et al. Pretreatment CT and 18F-FDG PET-based radiomic model predicting pathological complete response and loco-regional control following neoadjuvant chemoradiation in oesophageal cancer. J Med Imaging Radiat Oncol. 2021;65:102–11.

    Article  PubMed  Google Scholar 

  40. Herceptin® package insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103792s5250lbl.pdf. Updated Oct 2010. Accessed 16 Mar 2021.

  41. Metzger-Filho O, Winer EP, Krop I. Pertuzumab: optimizing HER2 blockade. Clin Cancer Res. 2013;19(20):5552–6.

    Article  CAS  PubMed  Google Scholar 

  42. Stroes CI, et al. Phase II feasibility and biomarker study of neoadjuvant trastuzumab and pertuzumab with chemoradiotherapy for resectable human epidermal growth factor receptor 2-positive esophageal adenocarcinoma: TRAP Study. J Clin Oncol. 2020;38(5):462–71.

    Article  CAS  PubMed  Google Scholar 

  43. Shitara K, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382:2419–30.

    Article  CAS  PubMed  Google Scholar 

  44. Jin Z, Yoon HH. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1. J Gastrointest Oncol. 2016;7(5):771–88.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Kelly RJ. The emerging role of immunotherapy for esophageal cancer. Curr Opin Gastroenterol. 2019;35(4):337–43.

    Article  PubMed  Google Scholar 

  46. Wakita A, et al. PD-L1 expression is a prognostic factor in patients with thoracic esophageal cancer treated without adjuvant chemotherapy. Anticancer Res. 2017;37(3):1433–41.

    Article  CAS  PubMed  Google Scholar 

  47. FDA approves pembrolizumab for advanced esophageal squamous cell cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-esophageal-squamous-cell-cancer. Issued: 31 July 2019. Accessed 16 Mar 2021.

  48. Kato K, et al. KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol. 2019;15(10):1057–66.

    Article  CAS  PubMed  Google Scholar 

  49. FDA approves nivolumab for esophageal squamous cell cancer. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-esophageal-squamous-cell-carcinoma. Issued: 11 June 2020. Accessed 16 Mar 2021.

  50. Kato K, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(11):1506–17.

    Article  CAS  PubMed  Google Scholar 

  51. Kim MK, et al. Value of complete metabolic response by F-18-fluorodeoxyglucose-positron emission tomography in oesophageal cancer for prediction of pathologic response and survival after preoperative chemoradiotherapy. Eur J Cancer. 2007;43:1385–91.

    Article  PubMed  Google Scholar 

  52. Wahl RL, et al. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–50S.

    Article  CAS  PubMed  Google Scholar 

  53. Eisenhauer EA, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  54. Yanagawa M, et al. Evaluation of response to neoadjuvant chemotherapy for esophageal cancer: PET response criteria in solid tumors versus response evaluation criteria in solid tumors. J Nucl Med. 2012;53(6):872–80.

    Article  CAS  PubMed  Google Scholar 

  55. Han S, et al. Prognostic and predictive values of interim 18F-FDG PET during neoadjuvant chemoradiotherapy for esophageal cancer: a systematic review and meta-analysis. Ann Nucl Med. 2021;35:447–57.

    Google Scholar 

  56. Wolchok JD, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412–20.

    Article  CAS  PubMed  Google Scholar 

  57. Kwak JJ, et al. Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune-related adverse events. Radiographics. 2015;35(2):424–37.

    Article  PubMed  Google Scholar 

  58. Weber JS, et al. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer. 2013;119(9):1675–82.

    Article  CAS  PubMed  Google Scholar 

  59. Khoja L, et al. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systemic review. Ann Oncol. 2017;28(10):2377–85.

    Article  CAS  PubMed  Google Scholar 

  60. Puzanov I, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Omloo JM, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg. 2007;246:992–1000.

    Article  PubMed  Google Scholar 

  62. de Vos-Geelen J, et al. Patterns of recurrence following definitive chemoradiation for patients with proximal esophageal cancer. Eur J Surg Oncol. 2021;47:2016–22.

    Google Scholar 

  63. Abate E, et al. Recurrence after esophagectomy for adenocarcinoma: defining optimal follow-up intervals and testing. J Am Coll Surg. 2010;210:428–35.

    Article  PubMed  Google Scholar 

  64. Goense L, et al. Diagnostic performance of F-18 FDG PET and PET/CT for the detection of recurrent esophageal cancer after treatment with curative intent: A systematic review and meta-analysis. J Nucl Med. 2015;56(7):995–1002.

    Article  PubMed  Google Scholar 

  65. van der Wilk BJ, et al. Active surveillance versus immediate surgery in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal cancer: a multicenter propensity matched study. Ann Surg. 2021;274:1009–16.

    Google Scholar 

  66. Kubota K, et al. Surgical therapy and chemoradiotherapy for postoperative recurrent esophageal cancer. Hepato-Gastroenterology. 2013;60(128):1961–5.

    PubMed  Google Scholar 

  67. Attia H, Smyth E. Evolving therapies in advanced oesophago-gastric cancers and the increasing role of immunotherapy. Expert Rev Anticancer Ther. 2021;21:535–46.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Imaging, Dana-Farber Cancer Institute, Boston, MA, USA

    Christopher G. Sakellis, Heather A. Jacene & Annick D. Van den Abbeele

  2. Department of Radiology, Brigham and Women’s Hospital, Boston, MA, USA

    Christopher G. Sakellis, Heather A. Jacene & Annick D. Van den Abbeele

  3. Harvard Medical School, Boston, MA, USA

    Christopher G. Sakellis, Heather A. Jacene & Annick D. Van den Abbeele

  4. Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Annick D. Van den Abbeele

  5. Tumor Imaging Metrics Core, Dana-Farber/Harvard Cancer Center, Boston, MA, USA

    Annick D. Van den Abbeele

Authors
  1. Christopher G. Sakellis
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  2. Heather A. Jacene
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  3. Annick D. Van den Abbeele
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Corresponding author

Correspondence to Annick D. Van den Abbeele .

Editor information

Editors and Affiliations

  1. Associate Professor and Director of Nuclear Medicine, University of Pisa, Pisa, Italy

    Duccio Volterrani

  2. Translational Research, Pisa University, PISA, Pisa, Italy

    Paola A. Erba

  3. Attending Emeritus, Memorial Sloan-Kettering Cancer Center Dept. Radiology, New York, NY, USA

    H. William Strauss

  4. Professor Emeritus, University of Pisa, Pisa, Italy

    Giuliano Mariani

  5. Attending Physician, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Steven M. Larson

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Sakellis, C.G., Jacene, H.A., Van den Abbeele, A.D. (2022). Diagnostic Applications of Nuclear Medicine: Esophageal Cancers. In: Volterrani, D., Erba, P.A., Strauss, H.W., Mariani, G., Larson, S.M. (eds) Nuclear Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-26067-9_41-2

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  • DOI: https://doi.org/10.1007/978-3-319-26067-9_41-2

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Chapter history

  1. Latest

    Diagnostic Applications of Nuclear Medicine: Esophageal Cancers
    Published:
    26 July 2022

    DOI: https://doi.org/10.1007/978-3-319-26067-9_41-2

  2. Original

    Diagnostic Applications of Nuclear Medicine: Esophageal Cancers
    Published:
    08 October 2016

    DOI: https://doi.org/10.1007/978-3-319-26067-9_41-1

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