Download PDF
CC BY 4.0 · Indian J Med Paediatr Oncol 2023; 44(02): 194-206
DOI: 10.1055/s-0042-1760311
Review Article

Imaging Recommendations for Diagnosis, Staging, and Management of Carcinoma of Unknown Origin (Lymph Node, Pulmonary, Liver, Skeletal, and Brain) with Emphasis on the Current Position of PET-CT in Carcinoma of Unknown Origin (CUP)

Sarvesh Loharkar
1   Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai, Maharashtra, India
2   Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Sandip Basu 
1   Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai, Maharashtra, India
2   Homi Bhabha National Institute, Mumbai, Maharashtra, India
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Most of the established guidelines mention and recommend the use of FDG-PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) in carcinoma of unknown primary (CUP) especially in head–neck squamous cell carcinoma; as described in this article, this forms a powerful one-stop shop in diagnosing and staging modality and has multiple applications in difficult situations of CUPs. Although not used as a screening modality, FDG-PET/CT is recommended as the primary imaging modality in the evaluation of primary, staging, and response evaluation for CUP with histology known to demonstrate FDG avidity, especially patients presenting with lymph nodal disease. It should be remembered that many histological types do not concentrate on FDG and FDG also shows false-positive results in many other conditions like infection-inflammation; however, at the same time, it delivers high negative predictive values, an important consideration when employing FDG-PET/CT in the CUP scenario. SSTR-based PET/CT plays a pivotal role in primary diagnosis, staging, therapy planning, and response assessment in CUPs with neuroendocrine tumor or neuroendocrine neoplasm histology. The last two decades has witnessed great advancement in PET instrumentation and radiopharmaceuticals: particularly techniques like PET/magnetic resonance imaging and radiopharmaceuticals like FAPI (fibroblast-activation protein inhibitor)-based PET tracers. Hence, the role of PET/CT is expected to expand its reach in the coming years in line with accruing literature evidence, thereby upgrading its role and reliability in oncological practice strategies.

Keywords

USG - PET - PET-CT - FDG - FNAC - biopsy - carcinoma of unknown primary (CUP)

Supplementary Material



Publication History

Article published online:
01 March 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Varghese AM, Arora A, Capanu M. et al. Clinical and molecular characterization of patients with cancer of unknown primary in the modern era. Ann Oncol 2017; 28 (12) 3015-3021
    CrossrefPubMedSearch in Google Scholar
  • 2 Rassy E, Nicolai P, Pavlidis N. Comprehensive management of HPV-related squamous cell carcinoma of the head and neck of unknown primary. Head Neck 2019; 41 (10) 3700-3711
    Search in Google Scholar
  • 3 Hemminki K, Chen B, Kumar A. et al. Germline genetics of cancer of unknown primary (CUP) and its specific subtypes. Oncotarget 2016; 7 (16) 22140-22149
    CrossrefPubMedSearch in Google Scholar
  • 4 Losa F, Iglesias L, Pané M. et al. 2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary. Clin Transl Oncol 2018; 20 (11) 1361-1372
    CrossrefPubMedSearch in Google Scholar
  • 5 Mathur P, Sathishkumar K, Chaturvedi M. et al; ICMR-NCDIR-NCRP Investigator Group. Cancer Statistics, 2020: Report From National Cancer Registry Programme, India. JCO Glob Oncol 2020; 6: 1063-1075
    CrossrefPubMedSearch in Google Scholar
  • 6 Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet 2012; 379 (9824): 1428-1435
    CrossrefPubMedSearch in Google Scholar
  • 7 Rassy E, Pavlidis N. The currently declining incidence of cancer of unknown primary. Cancer Epidemiol 2019; 61: 139-141
    CrossrefPubMedSearch in Google Scholar
  • 8 Qaseem A, Usman N, Jayaraj JS, Janapala RN, Kashif T. Cancer of unknown primary: a review on clinical guidelines in the development and targeted management of patients with the unknown primary site. Cureus 2019; 11 (09) e5552
    PubMedSearch in Google Scholar
  • 9 Maghami E, Ismaila N, Alvarez A. et al. Diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck: ASCO guideline. J Clin Oncol 2020; 38 (22) 2570-2596
    CrossrefPubMedSearch in Google Scholar
  • 10 Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G. ESMO Guidelines Committee. Cancers of unknown primary site: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (Suppl. 05) v133-v138
    CrossrefPubMedSearch in Google Scholar
  • 11 Scarbrook A. Carcinoma of unknown origin. In: Nicolson T. ed. Recommendations of Cross Sectional Imaging in Cancer Management. London: Royal College of Radiologists; 2014
    Search in Google Scholar
  • 12 Anbarasu A, Joshi V, Solanki R, Kumar J, Shah D. Head & Neck Imaging Sub Specialty Group Scanning Guidelines Ct Scan/Mr Imaging Version April; 2020. Accessed December 13, 2022 at: https://icri.iria.org.in/head-and-neck-imaging-guidelines-2020
  • 13 Boellaard R, Delgado-Bolton R, Oyen WJ. et al; European Association of Nuclear Medicine, (EANM). FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging 2015; 42 (02) 328-354
    CrossrefPubMedSearch in Google Scholar
  • 14 Hope TA, Bergsland EK, Bozkurt MF. et al. Appropriate use criteria for somatostatin receptor PET imaging in neuroendocrine tumors. J Nucl Med 2018; 59 (01) 66-74
    CrossrefPubMedSearch in Google Scholar
  • 15 Schöder H, Gönen M. Screening for cancer with PET and PET/CT: potential and limitations. J Nucl Med 2007; 48 (Suppl. 01) 4S-18S
    PubMedSearch in Google Scholar
  • 16 Kwee TC, Kwee RM. Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol 2009; 19 (03) 731-744
    CrossrefPubMedSearch in Google Scholar
  • 17 Rusthoven KE, Koshy M, Paulino AC. The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer 2004; 101 (11) 2641-2649
    CrossrefPubMedSearch in Google Scholar
  • 18 Lee JR, Kim JS, Roh JL. et al. Detection of occult primary tumors in patients with cervical metastases of unknown primary tumors: comparison of (18)F FDG PET/CT with contrast-enhanced CT or CT/MR imaging-prospective study. Radiology 2015; 274 (03) 764-771
    CrossrefPubMedSearch in Google Scholar
  • 19 De Wever W, Meylaerts L, De Ceuninck L, Stroobants S, Verschakelen JA. Additional value of integrated PET-CT in the detection and characterization of lung metastases: correlation with CT alone and PET alone. Eur Radiol 2007; 17 (02) 467-473
    CrossrefPubMedSearch in Google Scholar
  • 20 Park SB, Park JM, Moon SH. et al. Role of 18F-FDG PET/CT in patients without known primary malignancy with skeletal lesions suspicious for cancer metastasis. PLoS One 2018; 13 (05) e0196808
    CrossrefPubMedSearch in Google Scholar
  • 21 Houshmand S, Salavati A, Segtnan EA, Grupe P, Høilund-Carlsen PF, Alavi A. Dual-time-point imaging and delayed-time-point fluorodeoxyglucose-PET/computed tomography imaging in various clinical settings. PET Clin 2016; 11 (01) 65-84
    CrossrefPubMedSearch in Google Scholar
  • 22 Fei B, Schuster DM. PET molecular imaging-directed biopsy: a review. AJR Am J Roentgenol 2017; 209 (02) 255-269
    CrossrefPubMedSearch in Google Scholar
  • 23 Sampathirao N, Basu S. MIB-1 index-stratified assessment of dual-tracer PET/CT with 68Ga-DOTATATE and 18F-FDG and multimodality anatomic imaging in metastatic neuroendocrine tumors of unknown primary in a PRRT workup setting. J Nucl Med Technol 2017; 45 (01) 34-41
    CrossrefPubMedSearch in Google Scholar
  • 24 Fletcher JW, Djulbegovic B, Soares HP. et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med 2008; 49 (03) 480-508
    CrossrefPubMedSearch in Google Scholar
  • 25 Barrio M, Czernin J, Fanti S. et al. The impact of somatostatin receptor-directed PET/CT on the management of patients with neuroendocrine tumor: a systematic review and meta-analysis. J Nucl Med 2017; 58 (05) 756-761
    CrossrefPubMedSearch in Google Scholar
  • 26 Varadhachary, Gauri, James L.Abbruzzese. “Carcinoma of unknown primary.” Abeloff's Clinical oncology. Elsevier 2020; 1694-1702
    Search in Google Scholar
  • 27 Gupta T, Master Z, Kannan S. et al. Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2011; 38 (11) 2083-2095
    CrossrefPubMedSearch in Google Scholar
  • 28 Slevin F, Subesinghe M, Ramasamy S, Sen M, Scarsbrook AF, Prestwich RJ. Assessment of outcomes with delayed (18)F-FDG PET-CT response assessment in head and neck squamous cell carcinoma. Br J Radiol 2015; 88 (1052): 20140592
    CrossrefPubMedSearch in Google Scholar
  • 29 Marcus C, Ciarallo A, Tahari AK. et al. Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)-interreader reliability, accuracy, and survival outcomes. J Nucl Med 2014; 55 (09) 1411-1416
    CrossrefPubMedSearch in Google Scholar
  • 30 Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med 2009; 50 (Suppl. 01) 122S-150S
    CrossrefPubMedSearch in Google Scholar
  • 31 Cliffe H, Patel C, Prestwich R, Scarsbrook A. Radiotherapy response evaluation using FDG PET-CT-established and emerging applications. Br J Radiol 2017; 90 (1071): 20160764
    CrossrefPubMedSearch in Google Scholar
  • 32 Martin RC, Fulham M, Shannon KF. et al. Accuracy of positron emission tomography in the evaluation of patients treated with chemoradiotherapy for mucosal head and neck cancer. Head Neck 2009; 31 (02) 244-250
    CrossrefPubMedSearch in Google Scholar
  • 33 Evilevitch V, Weber WA, Tap WD. et al. Reduction of glucose metabolic activity is more accurate than change in size at predicting histopathologic response to neoadjuvant therapy in high-grade soft-tissue sarcomas. Clin Cancer Res 2008; 14 (03) 715-720
    CrossrefPubMedSearch in Google Scholar
  • 34 Lopci E, Hicks RJ, Dimitrakopoulou-Strauss A. et al. Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0. Eur J Nucl Med Mol Imaging 2022; 49 (07) 2323-2341
    CrossrefPubMedSearch in Google Scholar
  • 35 Ayati N, Sadeghi R, Kiamanesh Z, Lee ST, Zakavi SR, Scott AM. The value of 18F-FDG PET/CT for predicting or monitoring immunotherapy response in patients with metastatic melanoma: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2021; 48 (02) 428-448
    CrossrefPubMedSearch in Google Scholar
  • 36 Wong ANM, McArthur GA, Hofman MS, Hicks RJ. The advantages and challenges of using FDG PET/CT for response assessment in melanoma in the era of targeted agents and immunotherapy. Eur J Nucl Med Mol Imaging 2017; 44 (Suppl. 01) 67-77
    CrossrefPubMedSearch in Google Scholar
  • 37 Adnan A, Basu S. Discordance between histopathologic grading and dual-tracer PET/CT findings in metastatic NETs and outcome of 177Lu-DOTATATE PRRT: does in vivo molecular PET perform better from the viewpoint of prediction of tumor biology?. J Nucl Med Technol 2021; 50 (Suppl. 03) 248-255
    PubMedSearch in Google Scholar
  • 38 Ruhlmann V, Ruhlmann M, Bellendorf A. et al. Hybrid imaging for detection of carcinoma of unknown primary: a preliminary comparison trial of whole-body PET/MRI versus PET/CT. Eur J Radiol 2016; 85 (11) 1941-1947
    CrossrefPubMedSearch in Google Scholar
  • 39 Kumar R, Singh SK, Mittal BR. et al. Safety and diagnostic yield of 68Ga prostate-specific membrane antigen PET/CT-guided robotic-assisted transgluteal prostatic biopsy. Radiology 2022; 303 (02) 392-398
    CrossrefPubMedSearch in Google Scholar
  • 40 Kratochwil C, Flechsig P, Lindner T. et al. 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med 2019; 60 (06) 801-805
    CrossrefPubMedSearch in Google Scholar
  • 41 Gu B, Xu X, Zhang J. et al. The added value of 68Ga-FAPI PET/CT in patients with head and neck cancer of unknown primary with 18F-FDG-negative findings. J Nucl Med 2022; 63 (06) 875-881
    CrossrefPubMedSearch in Google Scholar
  • 42 Niederkohr RD, Greenspan BS, Prior JO. et al. Reporting guidance for oncologic 18F-FDG PET/CT imaging. J Nucl Med 2013; 54 (05) 756-761
    CrossrefPubMedSearch in Google Scholar