FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2904435401> ?p ?o ?g. }

• W2904435401 endingPage "1124" @default.
• W2904435401 startingPage "1109" @default.
• W2904435401 abstract "Perineural invasion (PNI), the neoplastic invasion of nerves, is a common pathologic finding in head and neck cancer that is associated with poor clinical outcomes. PNI is a histologic finding of tumor cell infiltration and is distinct from perineural tumor spread (PNTS), which is macroscopic tumor involvement along a nerve extending from the primary tumor that is by definition more advanced, being radiologically or clinically apparent. Despite widespread acknowledgment of the prognostic significance of PNI and PNTS, the mechanisms underlying its pathogenesis remain largely unknown, and specific therapies targeting nerve invasion are lacking. The use of radiation therapy for PNI and PNTS can improve local control and reduce devastating failures at the skull base. However, the optimal volumes to be delineated with respect to targeting cranial nerve pathways are not well defined, and radiation can carry risks of major toxicity secondary to the location of adjacent critical structures. Here we examine the pathogenesis of these phenomena, analyze the role of radiation in PNI and PNTS, and propose guidelines for radiation treatment design based on the best available evidence and the authors' collective experience to advance understanding and therapy of this ominous cancer phenotype. Perineural invasion (PNI), the neoplastic invasion of nerves, is a common pathologic finding in head and neck cancer that is associated with poor clinical outcomes. PNI is a histologic finding of tumor cell infiltration and is distinct from perineural tumor spread (PNTS), which is macroscopic tumor involvement along a nerve extending from the primary tumor that is by definition more advanced, being radiologically or clinically apparent. Despite widespread acknowledgment of the prognostic significance of PNI and PNTS, the mechanisms underlying its pathogenesis remain largely unknown, and specific therapies targeting nerve invasion are lacking. The use of radiation therapy for PNI and PNTS can improve local control and reduce devastating failures at the skull base. However, the optimal volumes to be delineated with respect to targeting cranial nerve pathways are not well defined, and radiation can carry risks of major toxicity secondary to the location of adjacent critical structures. Here we examine the pathogenesis of these phenomena, analyze the role of radiation in PNI and PNTS, and propose guidelines for radiation treatment design based on the best available evidence and the authors' collective experience to advance understanding and therapy of this ominous cancer phenotype. Perineural invasion (PNI) is a common pathologic finding in many head and neck cancers, including squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC; Table 1). Initial theories suggested that PNI was simply an extension of lymphatic metastasis, which was eventually disproven. Modern studies have demonstrated that PNI is a deliberate, molecularly mediated process that results from reciprocal interactions between cancer and nerve, challenging the historic notion that this is an event driven purely by the progress of cancer alone.1Bakst R.L. Wong R.J. Mechanisms of perineural invasion.J Neurol Surg B Skull Base. 2016; 77: 96-106Crossref PubMed Scopus (24) Google Scholar, 2Gil Z. Cavel O. Kelly K. et al.Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves.J Natl Cancer Inst. 2010; 102: 107-118Crossref PubMed Scopus (115) Google Scholar There is growing evidence that the supportive cells within peripheral nerves interact with the cancer and directly promote neoplastic invasion and dissemination along nerves.3Bakst R.L. Xiong H. Chen C.H. et al.Inflammatory monocytes promote perineural invasion via CCL2-mediated recruitment and cathepsin B expression.Cancer Res. 2017; 77: 6400-6414Crossref PubMed Scopus (2) Google Scholar, 4Deborde S. Omelchenko T. Lyubchik A. et al.Schwann cells induce cancer cell dispersion and invasion.J Clin Invest. 2016; 126: 1538-1554Crossref PubMed Scopus (40) Google Scholar, 5Demir I.E. Boldis A. Pfitzinger P.L. et al.Investigation of Schwann cells at neoplastic cell sites before the onset of cancer invasion.J Natl Cancer Inst. 2014; 106Crossref Scopus (40) Google ScholarTable 1Head and neck cancer types commonly associated with perineural invasionHistologyPrimary tumor siteAdenoid cystic carcinomaMajor or minor salivary glandsSalivary ductal carcinomaMajor or minor salivary glandsMucoepidermoid carcinomaMajor or minor salivary glandsSquamous cell carcinomaCutaneous or mucosal siteDesmoplastic melanomaCutaneous Open table in a new tab When reporting the pathology of head and neck cancer, the presence versus absence of PNI should be documented. Nevertheless, the histologic evaluation of PNI can be variable, and different patterns of tumor–nerve interaction are observed. Histologically, there are 3 connective tissue layers that comprise the nerve sheath: (1) the innermost endoneurium, which surrounds individual nerve fibers (axons and associated Schwann cells); (2) the perineurium, which surrounds individual nerve fascicles and is composed of endothelial cells vested by basal lamina; and (3) the outermost epineurium, which binds together several nerve fascicles to form larger nerves (Fig. 1).6Akert K. Sandri C. Weibel E.R. et al.The fine structure of the perineural endothelium.Cell Tissue Res. 1976; 165: 281-295Crossref PubMed Scopus (0) Google Scholar, 7Liebig C. Ayala G. Wilks J.A. et al.Perineural invasion in cancer: A review of the literature.Cancer. 2009; 115: 3379-3391Crossref PubMed Scopus (433) Google Scholar PNI is a histologic finding of tumor cell infiltration and is distinct from perineural tumor spread (PNTS), which is macroscopic tumor extension along a nerve from the primary tumor that is radiologically or clinically apparent. In 1985, Batsakis et al8Batsakis J.G. Nerves and neurotropic carcinomas.Ann Otol Rhinol Laryngol. 1985; 94: 426-427Crossref PubMed Google Scholar defined PNI as tumor cell invasion in, around, and through peripheral nerves and this remains the most commonly used definition of PNI. Furthermore, Liebig has specified that the presence of tumor cells within any of the 3 nerve sheath layers represents PNI and has expanded the PNI definition to include 2 histologic patterns of nerve involvement.7Liebig C. Ayala G. Wilks J.A. et al.Perineural invasion in cancer: A review of the literature.Cancer. 2009; 115: 3379-3391Crossref PubMed Scopus (433) Google Scholar The first pattern (type A) is identified when tumor cells are located within the peripheral nerve sheath and infiltration into the 3 nerve sheath layers can be distinguished. The second pattern (type B) is noted when tumor cells are seen in close proximity to the nerve and involve at least 33% of its circumference.7Liebig C. Ayala G. Wilks J.A. et al.Perineural invasion in cancer: A review of the literature.Cancer. 2009; 115: 3379-3391Crossref PubMed Scopus (433) Google Scholar The term intraneural invasion is used when tumor cells are noted to involve the innermost endoneurium (Fig. 1). Some investigators have regarded intraneural invasion as a subset of PNI that should be specifically reported, but there is currently insufficient evidence to determine whether intraneural invasion shows more aggressive behavior compared with other types of PNI.7Liebig C. Ayala G. Wilks J.A. et al.Perineural invasion in cancer: A review of the literature.Cancer. 2009; 115: 3379-3391Crossref PubMed Scopus (433) Google Scholar, 8Batsakis J.G. Nerves and neurotropic carcinomas.Ann Otol Rhinol Laryngol. 1985; 94: 426-427Crossref PubMed Google Scholar, 9Binmadi N.O. Basile J.R. Perineural invasion in oral squamous cell carcinoma: A discussion of significance and review of the literature.Oral Oncol. 2011; 47: 1005-1010Crossref PubMed Scopus (82) Google Scholar, 10Dunn M. Morgan M.B. Beer T.W. Perineural invasion: Identification, significance, and a standardized definition.Dermatol Surg. 2009; 35: 214-221Crossref PubMed Scopus (47) Google Scholar, 11Gil Z. Carlson D.L. Gupta A. et al.Patterns and incidence of neural invasion in patients with cancers of the paranasal sinuses.Arch Otolaryngol Head Neck Surg. 2009; 135: 173-179Crossref PubMed Scopus (49) Google Scholar In addition, determination of the exact histologic pattern of PNI can be difficult in practice, and deeper sections or immunohistochemistry, or both (ie, S100 and keratin), are necessary for determination of PNI in equivocal cases. PNI by head and neck cancers is a significant cause of morbidity and mortality, and it confers a poor prognosis.12Chinn S.B. Spector M.E. Bellile E.L. et al.Impact of perineural invasion in the pathologically n0 neck in oral cavity squamous cell carcinoma.Otolaryngol Head Neck Surg. 2013; 149: 893-899Crossref PubMed Scopus (43) Google Scholar, 13Fagan J.J. Collins B. Barnes L. D’Amico F. Myers E.N. Johnson J.T. Perineural invasion in squamous cell carcinoma of the head and neck.Arch Otolaryngol Head Neck Surg. 1998; 124: 637-640Crossref PubMed Google Scholar, 14Soo K.C. Carter R.L. O’Brien C.J. Barr L. Bliss J.M. Shaw H.J. Prognostic implications of perineural spread in squamous carcinomas of the head and neck.Laryngoscope. 1986; 96: 1145-1148Crossref PubMed Google Scholar PNI has been reported across many case series at varying prevalence rates of 25% to 80% of head and neck mucosal SCCs,15Baumeister P. Welz C. Jacobi C. Reiter M. Is perineural invasion of head and neck squamous cell carcinomas linked to tobacco consumption?.Otolaryngol Head Neck Surg. 2018; 158: 878-881Crossref PubMed Scopus (4) Google Scholar, 16Hinerman R.W. Mendenhall W.M. Morris C.G. Amdur R.J. Werning J.W. Villaret D.B. Postoperative irradiation for squamous cell carcinoma of the oral cavity: 35-year experience.Head Neck. 2004; 26: 984-994Crossref PubMed Scopus (112) Google Scholar, 17Kurtz K.A. Hoffman H.T. Zimmerman M.B. Robinson R.A. Perineural and vascular invasion in oral cavity squamous carcinoma: Increased incidence on re-review of slides and by using immunohistochemical enhancement.Arch Pathol Lab Med. 2005; 129: 354-359Crossref PubMed Google Scholar, 18Rahima B. Shingaki S. Nagata M. Saito C. Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004; 97: 423-431Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar and it constitutes a pervasive feature present in at least half of ACCs.19Barrett A.W. Speight P.M. Perineural invasion in adenoid cystic carcinoma of the salivary glands: A valid prognostic indicator?.Oral Oncol. 2009; 45: 936-940Crossref PubMed Scopus (96) Google Scholar, 20Dodd G.D. Jing B.S. Radiographic findings in adenoid cystic carcinoma of the head and neck.Ann Otol Rhinology Laryngol. 1972; 81: 591-598Crossref PubMed Google Scholar, 21Garden A.S. Weber R.S. Morrison W.H. Ang K.K. Peters L.J. The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation.Int J Radiat Oncol Biol Phys. 1995; 32: 619-626Abstract Full Text PDF PubMed Scopus (268) Google Scholar, 22Stambuk H.E. Perineural tumor spread involving the central skull base region.Semin Ultrasound CT MR. 2013; 34: 445-458Crossref PubMed Google Scholar Although PNI is rare in most skin cancers, it is seen in 36% to 50% of desmoplastic melanoma,23Anstey A. McKee P. Jones E.W. Desmoplastic malignant melanoma: A clinicopathological study of 25 cases.Br J Dermatol. 1993; 129: 359-371Crossref PubMed Scopus (0) Google Scholar, 24Carlson J.A. Dickersin G.R. Sober A.J. Barnhill R.L. Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases.Cancer. 1995; 75: 478-494Crossref PubMed Scopus (217) Google Scholar, 25Rutten A. Hügel H. Kutzner H. Schirren C.G. Küchler A. Groth W. Desmoplastic malignant melanoma. Clinical and histopathologic results of a study in 34 patients [in German].Hautarzt. 1996; 47: 447-453Crossref PubMed Scopus (0) Google Scholar and the rare cutaneous SCCs (<5%) that manifest with PNTS are remarkably resistant to treatment. The local extension of cancer cells along nerves is an ominous clinical event that is associated with increased local recurrence and worsened survival.7Liebig C. Ayala G. Wilks J.A. et al.Perineural invasion in cancer: A review of the literature.Cancer. 2009; 115: 3379-3391Crossref PubMed Scopus (433) Google Scholar, 13Fagan J.J. Collins B. Barnes L. D’Amico F. Myers E.N. Johnson J.T. Perineural invasion in squamous cell carcinoma of the head and neck.Arch Otolaryngol Head Neck Surg. 1998; 124: 637-640Crossref PubMed Google Scholar, 22Stambuk H.E. Perineural tumor spread involving the central skull base region.Semin Ultrasound CT MR. 2013; 34: 445-458Crossref PubMed Google Scholar, 26Goepfert H. Dichtel W.J. Medina J.E. Lindberg R.D. Luna M.D. Perineural invasion in squamous cell skin carcinoma of the head and neck.Am J Surg. 1984; 148: 542-547Abstract Full Text PDF PubMed Google Scholar PNI is considered an exacerbating feature that can worsen the prognosis of patients with surgical close margins,21Garden A.S. Weber R.S. Morrison W.H. Ang K.K. Peters L.J. The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation.Int J Radiat Oncol Biol Phys. 1995; 32: 619-626Abstract Full Text PDF PubMed Scopus (268) Google Scholar, 27Ch’ng S. Corbett-Burns S. Stanton N. et al.Close margin alone does not warrant postoperative adjuvant radiotherapy in oral squamous cell carcinoma.Cancer. 2013; 119: 2427-2437Crossref PubMed Scopus (0) Google Scholar and it has been associated with an increased risk of regional recurrence.18Rahima B. Shingaki S. Nagata M. Saito C. Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004; 97: 423-431Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 28Lanzer M. Gander T. Kruse A. Luebbers H.T. Reinisch S. Influence of histopathologic factors on pattern of metastasis in squamous cell carcinoma of the head and neck.Laryngoscope. 2014; 124: E160-E166Crossref PubMed Scopus (4) Google Scholar, 29Laske R.D. Scholz I. Ikenberg K. et al.Perineural invasion in squamous cell carcinoma of the oral cavity: Histology, tumor stage, and outcome.Laryngoscope Investig Otolaryngol. 2016; 1: 13-18Crossref PubMed Google Scholar, 30Tai S.K. Li W.Y. Chu P.Y. et al.Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma.Head Neck. 2012; 34: 994-1001Crossref PubMed Scopus (53) Google Scholar, 31Yang X. Tian X. Wu K. et al.Prognostic impact of perineural invasion in early stage oral tongue squamous cell carcinoma: Results from a prospective randomized trial.Surg Oncol. 2018; 27: 123-128Crossref PubMed Scopus (4) Google Scholar Conversely, PNTS is not associated with greater risk of regional metastasis, but the locally mediated morbidity can be severe. In cases of advanced uncontrolled PNTS, patients experience debilitating symptoms such as neuropathic pain, numbness or other sensory nerve dysfunction, paralysis, disfigurement, and injury from motor nerve dysfunction. In certain scenarios, major nerve invasion allows the tumor to track proximally from the distal branches of the nerve toward the central nervous system, potentially leading to tumor invasion into the skull base foramina, where major cranial nerves (CNs) are located.32Laine F.J. Braun I.F. Jensen M.E. Nadel L. Som P.M. Perineural tumor extension through the foramen ovale: Evaluation with MR imaging.Radiology. 1990; 174: 65-71Crossref PubMed Google Scholar Uncontrolled disease at the base of skull is difficult to treat, and it risks substantial intracranial morbidity. Over aggregated case series, there are a number of characteristics of nerve invasion that have been reported to increase locoregional and nerve-pathway failure. These characteristics include extent of PNI involvement and number of foci (eg, focal versus extensive; anecdotally, ≥2 nerves on microscopic evaluation of tumor specimen or ≥4 foci), caliber of the largest involved nerve diameter (0.1- or 1-mm cut points have been proposed depending on the specific case series), presence of “skipping” involvement longitudinally along the nerve, intraneural invasion, intratumoral versus extratumoral location of PNI, and involvement of a large-caliber or “named” nerve.13Fagan J.J. Collins B. Barnes L. D’Amico F. Myers E.N. Johnson J.T. Perineural invasion in squamous cell carcinoma of the head and neck.Arch Otolaryngol Head Neck Surg. 1998; 124: 637-640Crossref PubMed Google Scholar, 18Rahima B. Shingaki S. Nagata M. Saito C. Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004; 97: 423-431Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 28Lanzer M. Gander T. Kruse A. Luebbers H.T. Reinisch S. Influence of histopathologic factors on pattern of metastasis in squamous cell carcinoma of the head and neck.Laryngoscope. 2014; 124: E160-E166Crossref PubMed Scopus (4) Google Scholar, 33Aivazian K. Ebrahimi A. Low T.H. et al.Perineural invasion in oral squamous cell carcinoma: Quantitative subcategorisation of perineural invasion and prognostication.J Surgical Oncol. 2015; 111: 352-358Crossref PubMed Scopus (0) Google Scholar, 34Brandwein-Gensler M. Smith R.V. Wang B. et al.Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma.Am J Surg Pathol. 2010; 34: 676-688Crossref PubMed Scopus (146) Google Scholar, 35Bur A.M. Lin A. Weinstein G.S. Adjuvant radiotherapy for early head and neck squamous cell carcinoma with perineural invasion: A systematic review.Head Neck. 2016; 38: E2350-E2357Crossref PubMed Scopus (22) Google Scholar, 36Carter J.B. Johnson M.M. Chua T.L. Karia P.S. Schmults C.D. Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: An 11-year cohort study.JAMA Dermatol. 2013; 149: 35-41Crossref PubMed Scopus (84) Google Scholar, 37Chatzistefanou I. Lubek J. Markou K. Ord R.A. The role of perineural invasion in treatment decisions for oral cancer patients: A review of the literature.J Craniomaxillofac Surg. 2017; 45: 821-825Crossref PubMed Scopus (0) Google Scholar, 38Miller M.E. Palla B. Chen Q. et al.A novel classification system for perineural invasion in noncutaneous head and neck squamous cell carcinoma: Histologic subcategories and patient outcomes.Am J Otolaryngol. 2012; 33: 212-215Crossref PubMed Scopus (25) Google Scholar, 39Sapir E. Tolpadi A. McHugh J. et al.Skin cancer of the head and neck with gross or microscopic perineural involvement: Patterns of failure.Radiother Oncol. 2016; 120: 81-86Abstract Full Text Full Text PDF PubMed Google Scholar, 40Tai S.K. Li W.Y. Yang M.H. et al.Treatment for t1-2 oral squamous cell carcinoma with or without perineural invasion: Neck dissection and postoperative adjuvant therapy.Ann Surg Oncol. 2012; 19: 1995-2002Crossref PubMed Scopus (41) Google Scholar There have been controversies regarding the independent impact of these histologic features, and further classificatory development is needed to assess their clinical effect precisely.38Miller M.E. Palla B. Chen Q. et al.A novel classification system for perineural invasion in noncutaneous head and neck squamous cell carcinoma: Histologic subcategories and patient outcomes.Am J Otolaryngol. 2012; 33: 212-215Crossref PubMed Scopus (25) Google Scholar, 41Chi A.C. Katabi N. Chen H.S. Cheng Y.L. Interobserver variation among pathologists in evaluating perineural invasion for oral squamous cell carcinoma.Head Neck Pathol. 2016; 10: 451-464Crossref PubMed Scopus (5) Google Scholar Magnetic resonance imaging (MRI) is the most sensitive imaging method for the detection of extratumoral extension along a large nerve, which is referred to as perineural tumor spread (PNTS). PNTS can be subtle on imaging, and it usually requires careful evaluation over multiple sequences.42Moreira M.C.S. Dos Santos A.C. Cintra M.B. Perineural spread of malignant head and neck tumors: Review of the literature and analysis of cases treated at a teaching hospital.Radiol Bras. 2017; 50: 323-327Crossref PubMed Scopus (3) Google Scholar It has been suggested that because of this and perhaps also because of inadequate training of radiologists to look for it, PNTS on MRI might be missed frequently.43Ginsberg L.E. Reinterpretation of head and neck scans: Massive can of worms or call to action?.AJNR Am J Neuroradiol. 2002; 23: 1617-1618PubMed Google Scholar The T1-weighted sequence is often referred to as the head and neck anatomic sequence because it results in high signal intensity of fat-containing structures. Fat, being uniformly hyperintense, allows clear delineation of other soft tissue contours such that a mass or a thickened nerve can be recognized easily. The reliably bright signal intensity on T1-weighted images can obscure contrast enhancement; therefore, it is necessary to negate or null the fat signal on postcontrast T1-weighted images using fat-saturation pulses to increase conspicuity of subtle enhancement, particularly along nerves surrounded by fat. Although routine T1-weighted and post-gadolinium fat-saturated T1-weighted MRI sequences are the most useful for PNTS detection, different slice thicknesses are performed in different institutions and practices, and thus detection of PNTS might be obscured. At many institutions, 3-mm axial and coronal images through the skull base are routinely performed for all head and neck cancer indications. Thus, a clinical suspicion of PNTS should be conveyed when the MRI scan is ordered and the protocol is established to obtain the most ideal imaging parameters. Regardless of the MRI technique performed, clinical concern for PNTS should always be communicated because it will greatly increase the radiologist's degree of suspicion that this subtle finding might be present. Recent studies have investigated the role of positron emission tomography (PET) in PNTS44Dercle L. Hartl D. Rozenblum-Beddok L. et al.Diagnostic and prognostic value of 18F-FDG PET, CT, and MRI in perineural spread of head and neck malignancies.Eur Radiol. 2018; 28: 1761-1770Crossref PubMed Scopus (1) Google Scholar; however, PET has limited spatial resolution and low sensitivity for small-volume disease, as is most often apparent with PNTS. In addition, because normal brain tissue has a high fluorodeoxyglucose uptake, it is extremely difficult to detect PNTS at the skull base or extending intracranially. MRI remains the gold standard to detect tumor spread and to follow patients with or at risk for nerve invasion.45Lee H. Lazor J.W. Assadsangabi R. Shah J. An imager’s guide to perineural tumor spread in head and neck cancers: Radiological footprints on (18)F-FDG PET with CT and MRI correlates.J Nucl Med. 2018; ([Epub ahead of print]) (Available at:. Accessed October 16, 2018)https://doi.org/10.2967/jnumed.118.214312Crossref Google Scholar Radiation therapy is usually indicated after discovery of PNI in head and neck mucosal SCC,13Fagan J.J. Collins B. Barnes L. D’Amico F. Myers E.N. Johnson J.T. Perineural invasion in squamous cell carcinoma of the head and neck.Arch Otolaryngol Head Neck Surg. 1998; 124: 637-640Crossref PubMed Google Scholar, 18Rahima B. Shingaki S. Nagata M. Saito C. Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004; 97: 423-431Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 28Lanzer M. Gander T. Kruse A. Luebbers H.T. Reinisch S. Influence of histopathologic factors on pattern of metastasis in squamous cell carcinoma of the head and neck.Laryngoscope. 2014; 124: E160-E166Crossref PubMed Scopus (4) Google Scholar, 33Aivazian K. Ebrahimi A. Low T.H. et al.Perineural invasion in oral squamous cell carcinoma: Quantitative subcategorisation of perineural invasion and prognostication.J Surgical Oncol. 2015; 111: 352-358Crossref PubMed Scopus (0) Google Scholar, 34Brandwein-Gensler M. Smith R.V. Wang B. et al.Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma.Am J Surg Pathol. 2010; 34: 676-688Crossref PubMed Scopus (146) Google Scholar, 35Bur A.M. Lin A. Weinstein G.S. Adjuvant radiotherapy for early head and neck squamous cell carcinoma with perineural invasion: A systematic review.Head Neck. 2016; 38: E2350-E2357Crossref PubMed Scopus (22) Google Scholar, 36Carter J.B. Johnson M.M. Chua T.L. Karia P.S. Schmults C.D. Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: An 11-year cohort study.JAMA Dermatol. 2013; 149: 35-41Crossref PubMed Scopus (84) Google Scholar, 37Chatzistefanou I. Lubek J. Markou K. Ord R.A. The role of perineural invasion in treatment decisions for oral cancer patients: A review of the literature.J Craniomaxillofac Surg. 2017; 45: 821-825Crossref PubMed Scopus (0) Google Scholar, 40Tai S.K. Li W.Y. Yang M.H. et al.Treatment for t1-2 oral squamous cell carcinoma with or without perineural invasion: Neck dissection and postoperative adjuvant therapy.Ann Surg Oncol. 2012; 19: 1995-2002Crossref PubMed Scopus (41) Google Scholar cutaneous SCC,39Sapir E. Tolpadi A. McHugh J. et al.Skin cancer of the head and neck with gross or microscopic perineural involvement: Patterns of failure.Radiother Oncol. 2016; 120: 81-86Abstract Full Text Full Text PDF PubMed Google Scholar or salivary gland malignancies21Garden A.S. Weber R.S. Morrison W.H. Ang K.K. Peters L.J. The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation.Int J Radiat Oncol Biol Phys. 1995; 32: 619-626Abstract Full Text PDF PubMed Scopus (268) Google Scholar because of its association with local, regional, and nerve pathway recurrence. With the advent of highly conformal technologies, radiation given as definitive, adjuvant, or salvage treatment can simultaneously or selectively address all or some of these potential patterns of recurrence. The most common scenario in which radiation therapy is considered is after resection of a mucosal or skin SCC or salivary gland tumor in which PNI is reported in the pathologic specimen. One must determine whether radiation therapy is indicated in the context of other clinicopathologic factors and if so, how the radiation should be designed to address the various patterns of failure at risk in each particular case. The authors recommend adjuvant radiation in the following settings:•Cutaneous SCC of the head and neck with extensive microscopic PNI or involvement of large-caliber nerves•Aggressive salivary gland cancers such as ACC or salivary duct carcinoma (SDC) containing microscopic PNI•Mucosal SCC with extensive microscopic PNI•Any primary tumor demonstrating clinical or radiographic PNTS The extent of radiation target volumes and dose regimens are discussed in the following section. Radiation can also be used in the definitive setting for cases with unresectable PNTS. In patients with skin cancer with gross PNTS, radiation can effectively control disease in 50% to 57% of patients.46Balamucki C.J. Mancuso A.A. Amdur R.J. et al.Skin carcinoma of the head and neck with perineural invasion.Am J Otolaryngol. 2012; 33: 447-454Crossref PubMed Scopus (57) Google Scholar, 47Jackson J.E. Dickie G.J. Wiltshire K.L. et al.Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: Toward a risk-adapted treatment approach.Head Neck. 2009; 31: 604-610Crossref PubMed Scopus (40) Google Scholar, 48Moore B.A. Weber R.S. Prieto V. et al.Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck.Laryngoscope. 2005; 115: 1561-1567Crossref PubMed Scopus (166) Google Scholar There are also limited reports of the use of primary radiation therapy in unresectable or subtotally resected salivary gland tumors, primarily ACC, in which definitive radiation therapy can control disease for some time in 36% to 93% using photon or particle therapies.49Balamucki C.J. Amdur R.J. Werning J.W. et al.Adenoid cystic carcinoma of the head and neck.Am J Otolaryngol. 2012; 33: 510-518Crossref PubMed Scopus (61) Google Scholar, 50Douglas J.G. Laramore G.E. Austin-Seymour M. Koh W. Stelzer K. Griffin T.W. Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy.Int J Radiat Oncol Biol Phys. 2000; 46: 551-557Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 51Pommier P. Liebsch N.J. Deschler D.G. et al.Proton beam radiation therapy for skull base adenoid cystic carcinoma.Arch Otolaryngol Head Neck Surg. 2006; 132: 1242-1249Crossref PubMed Scopus (125) Google Scholar When designing target volumes in cases of PNI, it is essential to weigh the risk–benefit level in the decision to cover the relevant CN pathways electively in addition to the primary tumor bed (Table 2). The optimal radiation treatment volume with respect to tracing the CN back to the skull is not well defined and can carry a significant risk of toxicity. The decision to include elective CN pathways in addition to the primary tumor region depends on the extent of PNI, histology, margin status, and clinical presentation weighed against the additional morbidity of increasing the treatment volume. For cutaneous and mucosal SCC with microscopic PNI, a wide margin on the tumor bed should be treated given the enhanced potential for local recurrence, and the potentially increased risk to the regional lymphatics should be considered as well.13Fagan J.J. Collins B. Barnes L. D’Amico F. Myers E.N. Johnson J.T." @default.
• W2904435401 created "2018-12-22" @default.
• W2904435401 creator A5017031483 @default.
• W2904435401 creator A5020532224 @default.
• W2904435401 creator A5024957945 @default.
• W2904435401 creator A5071370261 @default.
• W2904435401 creator A5082685694 @default.
• W2904435401 creator A5083180697 @default.
• W2904435401 date "2019-04-01" @default.
• W2904435401 modified "2023-10-14" @default.
• W2904435401 title "Perineural Invasion and Perineural Tumor Spread in Head and Neck Cancer" @default.
• W2904435401 cites W1482490776 @default.
• W2904435401 cites W1509432611 @default.
• W2904435401 cites W1532654778 @default.
• W2904435401 cites W1841705709 @default.
• W2904435401 cites W1923197151 @default.
• W2904435401 cites W1956371911 @default.
• W2904435401 cites W1966603644 @default.
• W2904435401 cites W1967405323 @default.
• W2904435401 cites W1968359118 @default.
• W2904435401 cites W1974118332 @default.
• W2904435401 cites W1979547351 @default.
• W2904435401 cites W1979731116 @default.
• W2904435401 cites W1984871104 @default.
• W2904435401 cites W1986923525 @default.
• W2904435401 cites W1987049028 @default.
• W2904435401 cites W1988989967 @default.
• W2904435401 cites W1989482703 @default.
• W2904435401 cites W1994136786 @default.
• W2904435401 cites W1998504390 @default.
• W2904435401 cites W1998840537 @default.
• W2904435401 cites W1999152161 @default.
• W2904435401 cites W2004632736 @default.
• W2904435401 cites W2007918090 @default.
• W2904435401 cites W2012586259 @default.
• W2904435401 cites W2013083391 @default.
• W2904435401 cites W2017035167 @default.
• W2904435401 cites W2017194589 @default.
• W2904435401 cites W2017959086 @default.
• W2904435401 cites W2029604580 @default.
• W2904435401 cites W2031541193 @default.
• W2904435401 cites W2034232079 @default.
• W2904435401 cites W2041972418 @default.
• W2904435401 cites W2045034887 @default.
• W2904435401 cites W2046276846 @default.
• W2904435401 cites W2055140047 @default.
• W2904435401 cites W2057388449 @default.
• W2904435401 cites W2059533824 @default.
• W2904435401 cites W2070951010 @default.
• W2904435401 cites W2074254324 @default.
• W2904435401 cites W2075166004 @default.
• W2904435401 cites W2088073445 @default.
• W2904435401 cites W2089257078 @default.
• W2904435401 cites W2089933604 @default.
• W2904435401 cites W2091304381 @default.
• W2904435401 cites W2096388800 @default.
• W2904435401 cites W2100405709 @default.
• W2904435401 cites W2101817133 @default.
• W2904435401 cites W2110876229 @default.
• W2904435401 cites W2111944850 @default.
• W2904435401 cites W2112915889 @default.
• W2904435401 cites W2120068217 @default.
• W2904435401 cites W2120421863 @default.
• W2904435401 cites W2121965402 @default.
• W2904435401 cites W2124809808 @default.
• W2904435401 cites W2128813958 @default.
• W2904435401 cites W2128865339 @default.
• W2904435401 cites W2132198580 @default.
• W2904435401 cites W2134695884 @default.
• W2904435401 cites W2136537082 @default.
• W2904435401 cites W2138929226 @default.
• W2904435401 cites W2139725663 @default.
• W2904435401 cites W2145078756 @default.
• W2904435401 cites W2150090970 @default.
• W2904435401 cites W2151596048 @default.
• W2904435401 cites W2153643805 @default.
• W2904435401 cites W2155384808 @default.
• W2904435401 cites W2155752258 @default.
• W2904435401 cites W2157404055 @default.
• W2904435401 cites W2163076565 @default.
• W2904435401 cites W2169660224 @default.
• W2904435401 cites W2178947594 @default.
• W2904435401 cites W2183558237 @default.
• W2904435401 cites W2295663967 @default.
• W2904435401 cites W2296763339 @default.
• W2904435401 cites W2298317754 @default.
• W2904435401 cites W2306715392 @default.
• W2904435401 cites W2315504956 @default.
• W2904435401 cites W2316254512 @default.
• W2904435401 cites W2332642961 @default.
• W2904435401 cites W2341152357 @default.
• W2904435401 cites W2341288354 @default.
• W2904435401 cites W2342601931 @default.
• W2904435401 cites W2346031991 @default.
• W2904435401 cites W2406934748 @default.
• W2904435401 cites W2461131482 @default.
• W2904435401 cites W2506419502 @default.
• W2904435401 cites W2512477743 @default.

• next