Postoperative radiotherapy is recommended for all patients with cutaneous and non-cutaneous squamous cell carcinoma of the head and neck in the presence of clinical and incidental perineural infiltration. Perineural infiltration represents one of the most important adverse prognostic factors and may impact negatively patient outcomes. While guidelines exist for defining radiotherapy treatment volumes in patients with cutaneous squamous cell carcinoma and clinical perineural infiltration, there is a notable gap in the literature regarding recommendations for cases with incidental perineural infiltration and parotid involvement.
Methods:
A case of cutaneous squamous cell carcinoma of the auricular zone was proposed to an expert radiation oncologist panel.
Results:
The main issues concerned the inclusion of the surgical bed alone or the extension to the adjacent zone.
Conclusion:
This paper aims to provide a review of literature data and to propose a comprehensive approach to target volume definition in this setting of patients.
PorcedduSVDanielsCYomSS, et al. Head and Neck Cancer International Group (HNCIG) Consensus Guidelines for the Delivery of Postoperative Radiation Therapy in Complex Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN). Int J Radiat Oncol Biol Phys2020; 107: 641-651.
2.
El-NaggarAKChanJKCGrandisJRet al, editors. WHO Classification of Head and Neck Tumors (4th edition). Lyon, France: IARC, 2017.
3.
NuttingCMMordenJPBeasleyM, et al. COSTAR Investigators. Results of a multicentre randomised controlled trial of cochlear-sparing intensity-modulated radiotherapy versus conventional radiotherapy in patients with parotid cancer (COSTAR; CRUK/08/004). Eur J Cancer2018; 103: 249-258.
4.
MendenhallWMAmdurRJWilliamsLS, et al. Carcinoma of the skin of the head and neck with perineural invasion. Head Neck2002; 24: 78e83
5.
ClaymanGLLeeJJHolsingerFC, et al. Mortality risk from squamous cell skin cancer. J Clin Oncol2005; 23: 759–765
6.
GoepfertHDichtelWJMedinaJE, et al. Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg1984; 148: 542–547.
7.
FeaselAMBrownTJBogleMA, et al. Perineural invasion of cutaneous malignancies. Dermatol Surg2001; 27: 531–542.
8.
BakstRLGlastonburyCMParvathaneniU, et al. Perineural Invasion and Perineural Tumor Spread in Head and Neck Cancer. Int J Radiat Oncol Biol Phys2019; 103: 1109-1124.
9.
GallowayTJMorrisCGMancusoAA, et al. Impact of radiographic findings on prognosis for skin carcinoma with clinical perineural invasion. Cancer. 2005; 103: 1254 –1257.
10.
BatsakisJG.Nerves and neurotropic carcinomas. Ann Otol Rhinol Laryngol1985; 94: 426-427.
11.
OkadaYEiblGGuhaS, et al. Nerve growth factor stimulates MMP-2 expression and activity and increases invasion by human pancreatic cancer cells. Clin Exp Metastasis2004; 21: 285-292.
12.
BalamuckiCJManuscoAAAmdurRJ, et al. Skin carcinoma of the head and neck with perineural invasion. Am J Otolaryngol2012; 33: 447e454
13.
Garcia-SerraAHinermanRWMendenhallWM, et al. Carcinoma of the skin with perineural invasion. Head Neck2003; 25: 1027e1033
14.
HanARatnerD.What is the role of adjuvant radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion?Cancer2007; 109: 1053–1059.
15.
SapirETolpadiAMcHughJ, et al. Skin cancer of the head and neck with gross or microscopic perineural involvement: patterns of failure. Radiother Oncol2016; 120: 81–86.
16.
ZakhemGAPulavartyANCarucciJ, et al. Association of patient risk factors, tumor characteristics, and treatment modality with poor outcomes in primary cutaneous squamous cell carcinoma: A Systematic Review and Meta-analysis. JAMA Dermatol2023; 159: 160-171.
17.
KariaPSMorganFCRuizES, et al. Clinical and incidental perineural invasion of cutaneous squamous cell carcinoma: a systematic review and pooled analysis of outcomes data. JAMA Dermatol2017; 153: 781-788.
18.
CarterJBJohnsonMMChuaTL, et al. Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: an 11-year cohort study. JAMA Dermatol2013; 149: 35-41.
19.
RossASWhalenFMElenitsasR, et al. Diameter of involved nerves predicts outcomes in cutaneous squamous cell carcinoma with perineural invasion: an investigator-blinded retrospective cohort study. Dermatol Surg2009; 35: 1859-1866.
20.
SchmitdLBScanlonCSD’SilvaNJ.Perineural invasion in head and neck cancer. J Dent Res2018; 97: 742–750.
21.
SubramaniamN, et al. Factors affecting survival in surgically salvaged locoregional recurrences of squamous cell carcinoma of the tongue. J Oral Maxillofac Surg2018; 76: 1133.e1-1133.e6
22.
ChatterjeeD, et al. Tumor budding and worse pattern of invasion can predict nodal metastasis in oral cancers and associated with poor survival in early-stage tumors. Ear Nose Throat J2019; 98: E112–E119.
23.
LinCTripconyLKellerJ, et al. Cutaneous carcinoma of the head and neck with clinical features of perineural infiltration treated with radiotherapy. Clin Oncol (R Coll Radiol)2013; 25: 362-367.
24.
BakstRLLeeNHeS, et al. Radiation impairs perineural invasion by modulating the nerve microenvironment. PLoS One2012; 7: e39925.
25.
GobillotTAGreerMParvathaneniU, et al. Radiation therapy for low and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure. Head Neck2023; 45: 2323-2334.
26.
PriteshSKFrederickCMEmilySR. Clinical and incidental perineural invasion of cutaneous squamous cell carcinoma: A systematic review and pooled analysis of outcomes data. JAMA Dermatol2017;153(8):781-788. doi: 10.1001/jamadermatol.2017.1680.
27.
McCordMWMendenhallWMParsonsJT, et al. Skin cancer of the head and neck with incidental microscopic perineural invasion. Int J Radiat Oncol Biol Phys1999; 43: 591–595.
28.
WarrenTAPanizzaBPorcedduSV, et al. Outcomes after surgery and postoperative radiotherapy for perineural spread of head and neck cutaneous squamous cell carcinoma. Head Neck2016; 38: 824-831.
29.
MendenhallWMAmdurRJHinermanRW, et al. Skin cancer of the head and neck with perineural invasion. Am J Clin Oncol2007; 30: 93-96.
30.
JacksonJEDickieGJWiltshireKL, et al. Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: toward a risk-adapted treatment approach. Head Neck2009; 31: 604–610.
31.
ChenAMHarrisJPTjoaT, et al. Refining target volume coverage after parotidectomy for cutaneous squamous cell carcinoma: omission of the cervical neck from the radiation field. Adv Radiat Oncol2023; 9: 101306.
32.
HuMKimANHEmetoTI, et al. Metastatic cutaneous squamous cell carcinoma to the parotid: Adjuvant radiotherapy and treatment outcomes. J Med Radiat Sci2023; 70: 161-170.
33.
DonaEVenessMJCakirB, et al. Metastatic cutaneous squamous cell carcinoma to the parotid: the role of surgery and adjuvant radiotherapy to achieve best outcome. ANZ J Surg2003; 73: 692-696.
34.
KoHCGuptaVMouradWF, et al. A contouring guide for head and neck cancers with perineural invasion. Pract Radiat Oncol2014; 4: e247-58.
35.
GluckIIbrahimMPopovtzerA, et al. Skin cancer of the head and neck with perineural invasion: defining the clinical target volumes based on the pattern of failure. Int J Radiat Oncol Biol Phys2009; 74: 38-46.
36.
ZanoniDKPatelSGShahJP.Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of head and neck cancer: rationale and implications. Curr Oncol Rep2019; 21: 52.
ArmstrongKWardJHughesNM, et al. Guidelines for Clinical Target Volume Definition for Perineural Spread of Major Salivary Gland Cancers. Clin Oncol (R Coll Radiol)2018; 30: 773-779.
39.
MerlottiAAlterioDVigna-TagliantiR, et al. Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology - head and neck working group. Radiat Oncol2014; 9: 264.
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