Editorial
High Risk Nonmelanoma Skin Cancers of the Head and Neck
Roger Ove*
Department of Radiation Oncology, Case Western University, USA
*Corresponding author: Roger Ove, Department of Radiation Oncology, Case Western University, University Hospitals Seidman Cancer Center, Lorain, Ohio, USA
Published: 20 Mar, 2017
Cite this article as: Ove R. High Risk Nonmelanoma Skin
Cancers of the Head and Neck. Clin
Surg. 2017; 2: 1360.
Editorial
Skin cancer is the most common malignancy in the world, and occurs very commonly in the head
and neck. Squamous and basal cell carcinomas are by far the most common, and while both can be
locally advanced, the former has the capacity to be impact survival. Such locally advanced squamous
cell carcinomas of the head and neck do not readily fit existing clinical trials, and are generally
treated with a combination of surgery, radiotherapy, and sometimes chemotherapy. It is something
of a paradox that in a field (head and neck malignancies) where the majority of recommendations
have a foundation in clinical trials, the most common malignancy of the head and neck has almost
no clinical trial support, with the majority of recommendations based on retrospective data. The
reason for this disparity is that, fortunately, the majority of nonmelanomatous skin cancers are
early stage superficial cases, readily treated with surgery or radiotherapy. Locally advanced cases are
much rarer, but remain a serious clinical problem than can lead to substantial morbidity, in part due
to the potential for such cases to invade the cranial nerves and base of skull.
Locally advanced squamous cell carcinoma of the skin is comprised of those that are stage T2
or higher, node positive, exhibit bone or cartilage invasion, or present with extensive perineural
invasion or clinical nerve involvement. Perineural invasion (PNI) occurs in roughly 10% of
squamous cell cases, and can be either focal or extensive. The presence of clinically symptomatic
nerve invasion carries a worse prognosis. There is some evidence indicating that the presence of
perineural invasion also increases the risk of lymph node metastases. Published experience from
the University of Florida indicates that the presence of clinically evident perineural invasion, either
symptomatic or seen on imaging, leads to a worse prognosis, with 50% local failure and 40% disease
specific mortality [1-4].
A recent publication from the University of Michigan substantiates these findings, reporting
on their institutional experience over a 14 year period [5]. This series describes the outcomes of 102
patients, all presenting with squamous cell carcinoma of the skin of the head and neck, with either
gross or microscopic PNI. The majority were treated surgically, with some variation in the radiation
treatment volumes and technique over that 14 year period. This series confirmed the dismal outcomes
for patients with gross PNI, with 64% recurrence in the nerves at 2 years after being treated with
surgery and postoperative radiotherapy. All patients with such gross PNI received postoperative
radiotherapy. These researchers also found that a patient with microscopically extensive PNI has
a very high recurrence rate in the nerves with clinical progression of disease if they received no
postoperative radiotherapy. Radiotherapy to the involved and associated nerves and ganglia improved
DFS (in nerves) from 25% to 94%. For those with focal PNI the recurrence rate was relatively low
and the benefit of radiotherapy was not as significant. For those with extensive microscopic PNI,
postoperative radiotherapy conferred a substantial benefit both in terms of recurrence free survival
in the nerves and disease-free survival, and this would be expected to translate to a survival benefit,
given the prognosis of patients with such base of skull failures. It should be noted that there is no
universally accepted definition of extensive PNI. In the Michigan series it was defined as having
more than two nerves involved in the surgical specimen. Some researchers have suggested that
involvement of nerves greater than 0.1mm in diameter confers a worse prognosis. An interesting
finding in the Michigan series is that for patients presenting with clinically involved nerves, failure
were seen in other cranial nerves. This was attributed to crossover between cranial nerves, typically
5 and 7. Another explanation would be that the peripheral skin cancers with PNI could infiltrate
along any nerves that innervate the region involved. The recommendations from Michigan were to
cover the base of skull and nerve ganglia to at least 60 Gray as tolerated by the brainstem and other
critical structures, and the entire involved dermatome should be irradiated.
Another recent publication on the topic, from the University of
Florida, documents their experience over a 28 year span, describing
the outcome of locally squamous skin cancer patients that received
elective nodal radiation [6]. In 1985 it became the practice of that
institution to offer such extended field radiotherapy for high risk cases.
These were primarily surgical patients that received postoperative
therapy. Patients whose elective nodal radiotherapy required little
modification of the primary site fields were not included. This
somewhat weakens the conclusions of the paper, as the outcome of
the excluded patients is not documented, or how limited the fields
actually were. The majority of patients in this series had a gross PNI
(13%) or microscopic PNI (78%) on pathological evaluation. Only 71
patients were evaluated over a 28 year span, indicating how difficult
it would be to perform a clinical trial for this population at any single
institution. The University of Florida found a very low neck failure
rate of only 4% in patients that received elective nodal irradiation in
this setting. Similarly, in the University of Michigan series, radiated
patients also received elective neck radiotherapy and a low neck failure
rate was documented. In contrast, a British Columbia series of locally
advanced cases treated definitively with radiotherapy documented
a high neck failure rate for the higher T-stage cases, in the absence
of such elective neck irradiation [7]. Together these series illustrate
the importance of recognizing extensive PNI in locally advanced
cases, and the importance of adjuvant radiotherapy covering the
appropriate base of skull and dermatome innervations, as well as the
regional nodal basins.
In the British Columbia series as well as others, local failure
or base of skull failure with squamous cell carcinoma was the
predominant cause of death. Aggressive management of such high
risk cases is warranted. MD Anderson reported on their experience
with aggressive multimodality management of such cases, usually
incorporating base of skull surgery followed by adjuvant therapy, and
such an approach had a substantial impact on this pattern of failure
[8].
Clinical trials are lacking in this area, in large part because
of the relative rarity of these high risk cases. Although concurrent
postoperative chemoradiation is not substantiated by any clinical trial
data, currently both NCCN and ACR recommend extrapolating from
head and neck mucosal postoperative chemoradiation trials to justify
the addition of chemotherapy to the regiment for high risk cases. A
clinical trial was recently completed by the Trans-Tasman Radiation
Oncology Group (TROG), offering postoperative radiotherapy (60-
66Gy) with concurrent carboplatin. Results are pending. This group
is to be commended on completing this important trial, and further
clinical research in this area is indicated.
References
- Mendenhall WM, Amdur RJ, Hinerman RW, Cognetta AB, Mendenhall NP. Radiotherapy for cutaneous squamous and basal cell carcinomas of the head and neck. Laryngoscope. 2009; 119: 1994-1999.
- Mendenhall WM, Amdur RJ, Hinerman RW, Werning JW, Malyapa RS, Villaret DB, et al. Skin cancer of the head and neck with perineural invasion. Am J Clin Oncol. 2007; 30: 93-96.
- Mendenhall WM, Amdur RJ, Williams LS, Mancuso AA, Stringer SP, Price Mendenhall N. Carcinoma of the skin of the head and neck with perineural invasion. Head Neck. 2002; 24: 78-83.
- Mendenhall WM, Ferlito A, Takes RP, Bradford CR, Corry J, Fagan JJ, et al. Cutaneous head and neck basal and squamous cell carcinomas with perineural invasion. Oral Oncol. 2012; 48: 918-922.
- Sapir E, Tolpadi A, McHugh J, Samuels SE, Elalfy E, Spector M, et al. Skin cancer of the head and neck with gross or microscopic perineural involvement: Patterns of failure. Radiother Oncol. 2016; 120: 81-86.
- Wray J, Amdur RJ, Morris CG, Werning J, Mendenhall WM. Efficacy of elective nodal irradiation in skin squamous cell carcinoma of the face, ears, and scalp. Radiat Oncol. 2015; 10: 199.
- Kwan W, Wilson D, Moravan V. Radiotherapy for locally advanced basal cell and squamous cell carcinomas of the skin. Int J Radiat Oncol Biol Phys. 2004; 60: 406-411.
- Raza SM, Ramakrishna R, Weber RS, Kupferman ME, Gidley PW, Hanna EY, et al. Nonmelanoma cutaneous cancers involving the skull base: outcomes of aggressive multimodal management. J Neurosurg. 2015; 123: 781-788.