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Review
. 2020 Apr;40(SUPPL. 1):S1-S86.
doi: 10.14639/0392-100X-suppl.1-40-2020.

Metastatic disease in head & neck oncology

Paolo Pisani  1 , Mario Airoldi  2 , Anastasia Allais  3 , Paolo Aluffi Valletti  4 , Mariapina Battista  1 , Marco Benazzo  5 , Roberto Briatore  1 , Salvatore Cacciola  1 , Salvatore Cocuzza  6 , Andrea Colombo  1 , Bice Conti  7   8 , Alberto Costanzo  1 , Laura Della Vecchia  9 , Nerina Denaro  10 , Cesare Fantozzi  1 , Danilo Galizia  11 , Massimiliano Garzaro  4 , Ida Genta  7   8 , Gabriela Alejandra Iasi  12 , Marco Krengli  13   14 , Vincenzo Landolfo  1 , Giovanni Vittorio Lanza  15 , Mauro Magnano  3 , Maurizio Mancuso  15 , Roberto Maroldi  16 , Laura Masini  13 , Marco Carlo Merlano  10   11 , Marco Piemonte  17 , Silvia Pisani  18 , Adriele Prina-Mello  19   20 , Luca Prioglio  21 , Maria Gabriella Rugiu  17 , Felice Scasso  21 , Agostino Serra  22   23 , Guido Valente  14 , Micol Zannetti  14 , Angelo Zigliani  16
Affiliations
Review

Metastatic disease in head & neck oncology

Paolo Pisani et al. Acta Otorhinolaryngol Ital. 2020 Apr.

Abstract

La malattia metastatica in oncologia testa-collo.

Riassunto: Il distretto testa e collo rappresenta una delle più comuni sedi di insorgenza di malattie oncologiche, con una percentuale di disseminazioni metastatiche elevata tanto a livello loco-regionale quanto a distanza. La prognosi di questi tumori è strettamente legata ad alcuni fattori principali: a) lo stadio della malattia; b) le recidive loco-regionali; c) le metastasi a distanza. Nei tumori della testa e del collo le metastasi a distanza sono presenti in circa il 10% dei casi al momento della prima diagnosi e si rendono evidenti nel corso della malattia in un ulteriore 20%-30% dei casi. Quando una metastasi a distanza a partenza da un tumore della testa e del collo si rende evidente, la prognosi viene usualmente considerata infausta, con una sopravvivenza media stimabile intorno ai 10 mesi. Scopo del presente lavoro è quello di fornire un up-todate aggiornato ed esaustivo in tema di metastasi a distanza in oncologia cervico-cefalica alla luce delle più recenti conoscenze. Concetti di recente acquisizione quali l’assetto molecolare dei tumori, le possibili interazioni tra cellule tumorali e tessuti, le peculiarità della malattia oligometastatica, il ruolo dell’immunoterapia… stanno profondamente cambiando l’approccio terapeutico in questi pazienti, con interessanti ricadute in tema di controllo di malattia. I primi capitoli sono dedicati alla storia naturale ed all’epidemiologia delle metastasi a distanza nei tumori della testa e del collo ed al loro inquadramento diagnostico anatomo-patologico e radiologico. Nei capitoli successivi vengono focalizzate le più rilevanti peculiarità cliniche con particolare attenzione agli argomenti di recente attualità quali le metastasi a distanza da tumori EBV ed HPV positivi ed il concetto di malattia oligometastatica. Ampio spazio viene destinato alle varie opzioni terapeutiche con particolare attenzione al sempre più rilevante ruolo dell’immunoterapia ed allo sviluppo di nuove tecnologie terapeutiche. In conclusione, vengono focalizzate le problematiche etico-cliniche legate al concetto di fragilità del paziente oncologico e le crescenti difficoltà di una sostenibile governance socio-economica.

Keywords: chemotherapy; distant metastasis; head and neck oncology; immunotherapy; nanomedicine; radiotherapy.

Plain language summary

The head and neck district represents one of the most frequent sites of cancer, and the percentage of metastases is very high in both loco-regional and distant areas. Prognosis refers to several factors: a) stage of disease; b) loco-regional relapses; c) distant metastasis. At diagnosis, distant metastases of head and neck cancers are present in about 10% of cases with an additional 20-30% developing metastases during the course of their disease. Diagnosis of distant metastases is associated with unfavorable prognosis, with a median survival of about 10 months. The aim of the present review is to provide an update on distant metastasis in head and neck oncology. Recent achievements in molecular profiling, interaction between neoplastic tissue and the tumor microenvironment, oligometastatic disease concepts, and the role of immunotherapy have all deeply changed the therapeutic approach and disease control. Firstly, we approach topics such as natural history, epidemiology of distant metastases and relevant pathological and radiological aspects. Focus is then placed on the most relevant clinical aspects; particular attention is reserved to tumours with distant metastasis and positive for EBV and HPV, and the oligometastatic concept. A substantial part of the review is dedicated to different therapeutic approaches. We highlight the role of immunotherapy and the potential effects of innovative technologies. Lastly, we present ethical and clinical perspectives related to frailty in oncological patients and emerging difficulties in sustainable socio-economical governance.

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Figures

Figure 2.1.
Figure 2.1.
Overall percentage of DM incidence by subsite ,,,,,,.
Figure 2.2.
Figure 2.2.
Overall risk percentage of DM according to T and N ,,,.
Figure 2.3.
Figure 2.3.
Overall percentages of DM in HNSCC for tumor stages .
Figure 4.1.
Figure 4.1.
CT demonstration of multiple cavitated (straight arrows) and solid (curved arrows) pulmonary metastases from a recurrent squamous cell carcinoma of the tongue at 8 weeks after completion of chemotherapy.
Figure 4.2.
Figure 4.2.
Bone metastasis replacing a large portion of the right acetabulum (arrows) imaged by multidetector CT in the axial plane and precisely mapped through multiplanar reconstructions obtained in the coronal and sagittal planes. The patient underwent RT.
Figure 4.3.
Figure 4.3.
FDG-PET shows a metastasis within the right lobe of the liver (straight arrow) from a HPV-positive squamous cell carcinoma of the left palatine tonsil (curved arrows).
Figure 4.4.
Figure 4.4.
Nasopharyngeal undifferentiated carcinoma in a young patient. (A) The FDG-PET/CT shows a metabolic active adenopathy at level 2b, on the left side of the neck, and a large bone metastases (B) in the left ala of the sacrum, both showing a high metabolic activity. While the CT image obtained during the PET/CT study does not demonstrate sufficient changes of the bony architecture (D), the MRI examination clearly defines the metastasis replacing the posterior aspect of the ala of the sacrum (arrows) and the peritumoural bone oedema (C).
Figure 4.5.
Figure 4.5.
Adenosquamous carcinoma of the right submandibular gland. Contrast enhanced CT (A) and the gradient-echo fat-saturation T1 weighted MRI post gadolinium (B) show a solid lesion arising from the right submandibular gland. The intra-glandular calcification demonstrated by CT falsely suggested chronic inflammation. A destructive and enhancing bone metastasis replacing a large portion of the right basiocciput is demonstrated by CT (D). CT-guided biopsy of the destructive bone metastasis (E). The staging was completed by a whole-body FDG-PET/CT that showed the primary tumour (arrow on C) and a synchronous metastasis of the spine (arrow in F).
Figure 4.6.
Figure 4.6.
Adenoid cystic carcinoma of the parotid gland (solid component > 30%, perineural spread). Left image: at initial staging the chest CT (coronal MPR) demonstrates two metastases within the left lower lobe (arrows). Central image: follow up CT 3 years after radical parotidectomy with facial nerve sacrifice, lymphadenectomy, CHT-RT and wedge resections of lungs nodules. New nodules and the sequelae of previous surgery are present. Right image: the CT follow-up at 1 year shows the progression of size of lung metastases and appearance of new ones (arrows).
Figure 6.1.
Figure 6.1.
Role of genetic alterations and EBV infection in NPC progression (from Nakanishi et al.,2017 , mod.).
Figure 9.1.
Figure 9.1.
Stereotactic radiotherapy for pulmonary metastasis from oropharynx cancer (stage T4 N2c M1): total dose 45 Gy, 15 Gy/fr.
Figure 9.2.
Figure 9.2.
SBRT on liver metastasis: total dose 45 Gy, 15 Gy/fr.
Figure 9.3.
Figure 9.3.
Patient affected by bone metastasis of the cervical spine (C1-C2-C4) from sinonasal cancer (stage T3 N2 M1) treated with SBRT: total dose 21 Gy, 7 Gy/fr.
Figure 9.4.
Figure 9.4.
Brain metastasis in the anterior-right portion of temporal lobe treated with stereotactic radiotherapy: total dose prescription 24 Gy in a single fraction.
Figure 13.1.
Figure 13.1.
(A) 3D cancer organoid model; (B) microfluidic organ-on-a-chip cancer model (created with biorender.com).
Figure 13.2.
Figure 13.2.
Nanostrucuture classification depending on material composition with specific description and, respectively, pros and cons in the nanomedicine field.
See this image and copyright information in PMC

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