Can Squamous Skin Cancer Efffect Nerves

Int J Radiat Oncol Biol Phys. Author manuscript; available in PMC 2010 May 1.

Published in final edited course every bit:

PMCID: PMC2702210

NIHMSID: NIHMS111706

Skin Cancer of the Head and Neck with Perineural Invasion: Defining the Clinical Target Volumes Based on the Pattern of Failure

Iris Gluck, Medico,^* Mohannad Ibrahim, MD,^** Aron Popovtzer, Md,^* Theodoros North. Teknos, MD,^*** Douglas B Chepeha, MD,^*** Mark Eastward Prince, Md,^*** Jeffrey S Moyer, MD,^*** Ballad R Bradford, MD,^*** and Avraham Eisbruch, Doctor^*

Iris Gluck

^* Department of Radiation Oncology, University of Michigan, Ann Arbor MI

Mohannad Ibrahim

^** Section of Radiology, Academy of Michigan, Ann Arbor MI

Aron Popovtzer

^* Department of Radiation Oncology, University of Michigan, Ann Arbor MI

Theodoros N. Teknos

^*** Department of Caput and Neck Surgery, University of Michigan, Ann Arbor MI

Douglas B Chepeha

^*** Section of Caput and Neck Surgery, University of Michigan, Ann Arbor MI

Mark E Prince

^*** Section of Head and Cervix Surgery, Academy of Michigan, Ann Arbor MI

Jeffrey S Moyer

^*** Department of Head and Neck Surgery, University of Michigan, Ann Arbor MI

Carol R Bradford

^*** Department of Caput and Cervix Surgery, Academy of Michigan, Ann Arbor MI

Avraham Eisbruch

^* Section of Radiation Oncology, University of Michigan, Ann Arbor MI

Abstract

Purpose

To analyze patterns of failure in patients with head and neck cutaneous squamous prison cell carcinoma (HNCSCC) and clinical/radiological evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning.

Methods

Patients treated with 3D conformal or intensity modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiological studies has been conducted.

Results

Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients received multiple surgical procedures and RT courses. The most prevalent failure pattern was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the principal nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several singled-out patterns of disease spread along specific CNs depending on the peel regions harboring the primary tumors, including multiple branches of CN 5 and VII. These patterns and the pertinent anatomy are detailed in the paper.

Conclusions

Predictable disease spread patterns along cranial fretfulness supplying the main tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the footing for CTV definition and delineation for RT handling planning.

Keywords: Skin cancer, Head and neck, IMRT, Target definition

INTRODUCTION

Perineural invasion (PNI) is identified in approximately iii.seven% of head and cervix cutaneous squamous cell carcinoma (HNCSCC) cases ^one. In addition to beingness associated with increased hazard of regional and distant metastases ^ane ^, ^two, PNI is most prominently associated with increased chance of local recurrences, including recurrences in both the skin and in cranial nerves (CNs). Together, these local recurrences account for the bulk of failures following definitive treatment ⁱⁱⁱ ^, ⁴.

In cases with clinical or radiological testify for CN interest the term clinical PNI (CPNI) is used ² ^, ^five, while for cases in which PNI is incidentally institute on pathologic examination, the term microscopic PNI (MPNI) is used.

Radiotherapy (RT) has a key role in the treatment of HNCSCC with CPNI, either as adjuvant treatment following surgical resection, or equally definitive handling for unresectable illness. The need to irradiate cranial nerves close to organs at risk (e.g. optic structures, brain and inner ear) accounts for the loftier rate (>30%) of complications associated with RT in these cases ^four ^, ^{half dozen}. Using conformal or intensity modulated RT may improve the therapeutic index of treatment. For purposes of highly conformal RT, the definition and delineation of the clinical target volumes (CTVs) for regions at risk of subclinical disease is of utmost importance. A systematic analysis of recurrence patterns supporting guidelines for CTV depiction is lacking.

We accept encountered several patients with MPNI or CPNI with treatment failures following conformal RT or IMRT. These failures were due to CPNI progression that seemed to follow distinct patterns. The aim of this paper is to analyze the patterns of disease progression and treatment failures, compare these failures with the targets chosen for irradiation, and review the relevant anatomy and pertinent literature, in an attempt to outline guidelines for target volume delineation in the handling of HNCSCC with CPNI.

METHODS

Patients were retrospectively identified through the information-base of operations of the Radiation Oncology department. Inclusion criteria were:

Histologically proven HNCSCC.
Diagnosis of CPNI- biopsy proven CN interest or clinical CN dysfunction in nerves distributed to the principal skin tumor site. Magnetic resonance imaging (MRI) findings without histological evidence for PNI or CN dysfunction were not sufficient to establish the diagnosis of CPNI.
Handling with RT for the index cancer at any disease stage.
CPNI resulting from the primary skin tumor (as opposed to CN involvement by an advanced nodal disease).

The information was nerveless retrospectively from the medical charts. RT plans and imaging studies were systematically reviewed.

Kaplan-Meier assay was used for calculation of progression free survival and overall survival.

RESULTS

The clinical features, treatments and outcome of patients are summarized in Tables 1 and 2. Patient numbers throughout the paper relate to these Tables.

Tabular array 1

Radiotherapy (RT,) patterns of failure, and result.

RT later surgical resection is designated "adjuvant" and RT to an uninvolved site is designated "elective". In all other cases RT was delivered for gross disease.

	Target and intent in 1^st RT course	Site of failure later 1^st RT form	Target and intent in 2^nd RT course	Site of failure after 2^nd RT grade	Survival after the diagnosis of CPNI (months)	current status
ane	nerves^*	treated nerves	nerves	N/A^†	66m	alive
ii	skin-adjuvant^*	nerves	nerves	contiguous nerves	17m	live
three	peel and fretfulness	peel and contiguous nerves	nerves-palliative		60m	dead
4	skin-adjuvant	nerves	nerves	face-to-face nerves	80m	alive
5	skin-adjuvant^*	skin and fretfulness	skin and fretfulness-adjuvant	N/A^†	4m	alive
6	peel-adjuvant^*	skin and nerves	skin and nerves-adjuvant, nodes-constituent	skin and face-to-face nerves	22m	dead
vii	skin and nerves – adjuvant, nodes-elective	contiguous nerves	nerves	treated and face-to-face nerves	13m	alive
8	skin and fretfulness-adjuvant, nodes-elective	N/A^†			39m	live
nine	Skin and nerves. nodes-elective	N/A^†			10m	alive
10	peel-adjuvant	nerves contiguous	nerves-palliative	radiotherapy discontinued later on 12.5 Gy	2m	dead
11A^††	Nerves. Nodes-elective.	fretfulness	nerves	N/A	28m	alive
11B	Skin. Nerve and nodes-elective.	contiguous nerve			28m	alive

Tabular array 2

Details of perineural invasion, radiotherapy (RT) for cranial fretfulness (CNs) and patterns of failure in CNs.

These results summarize clinical (C), radiological(R), and surgical (Southward) data. Involvement of trigeminal ganglion, auriculotemporal nerve (ATN) and greater superficial petrosal nerve (GSPN) was always identified radiologically.

	Site of primary	Neural target in first RT form to nerves	Site of failure following first RT course to nerves	Site of failure following second RT form to nerves	CN interest, sequence of events
1	primary not identified	CN Five, VII and clangorous sinus	Treated nerves		V2-3(C), Seven(C), trigeminal ganglion
2	temple	V2-3 and cavernous sinus	V1 and CN VII		temporal branch of facial nerve(S), V1-3(C), trigeminal ganglion, GSPN, Vii(C), III, IV, Half dozen(C)
iii	forehead	V1 and clangorous sinus	V3		V1(C), trigeminal ganglion, V2-3(C), 7(C), Three, IV, Six (C)
4	medial cheek	V2-three and clangorous sinus	V1 and CN Vii		V2-3(C), GSPN, Vii(C), V1 (C), trigeminal ganglion, III, Iv, 6 (C)
five	lateral eyebrow	V1			V1(S)
vi	preauricular	CN Vii	ATN and V3		Vii(C), V3(C,R)+ATN
vii	ear	CN VII	ATN and V3	V2, inferior alveolar verve, cysternal segment of CN Five	VII(C), ATN+ V3(R), trigeminal ganglion, V2(R)
8	cheek	CN VII, ATN, V3			VII(Southward), ATN, V3(S)
9	cheek	CN 7, ATN, V3			Vii(C), ATN, V3(R)
10	nasal ala	CN Seven and V			VII(C), V(C)
11A	primary not identified	left V3	left CN Vii		left V3(C), VII(C)
11B	ear	correct CN VII (excluding the cochlea)	right tympanic portion of CN Seven		right Seven(C)

Clinical Findings

Initial presentation of skin cancer

Xi patients, treated with RT betwixt the years 2000–2007 for twelve HNCSCCs with CPNI, fulfilled the inclusion criteria. The median historic period at the time of diagnosis was 67 years (range 53–89 years), and there was male predominance (male/female ratio 8/3).

Three patients had received chronic immunosuppressive handling; two for kidney transplant (patients ten and 11) and one for Wegener's granulomatosis (patient 7). The majority of patients were initially treated in other facilities for the primary pare cancer; therefore, information was defective regarding the clinical characteristics of the primary skin tumor (eastward.k. size, depth). Half-dozen tumors were moderately or poorly differentiated and three were well differentiated. MPNI was histologically identified in five primary tumors and three cutaneous recurrences.

Details of CPNI

The typical presentation of CPNI was focal CN V or 7 dysfunction. Common symptoms included numbness, hurting or paresthesia in the distribution of the affected segmentation of CN Five and focal facial palsy. In three cases the first evidence for CPNI was nerve involvement constitute during surgery (Table two).

The design of primary CN involvement reflected the innervation of primary peel tumor sites and the proximity of this site to major nerve trunks; periauricular tumors in patients six, 7, viii, 9 and 11b infiltrated CN VII, supraorbital tumors in patients 3 and 5 infiltrated V1, and a medial cheek tumor in patient four infiltrated V2. Patient two had a tumor of the temporal expanse that involved both V2–3 and CN VII at an early stage.

The bulk of cases (excluding patient 8) presented with a single nerve involvement; later on, in x cases, involvement of additional nerves was observed afterwards less than i twelvemonth.

The mechanism of secondary CNs involvement could be elucidated in the following cases (Tabular array 2):

In iv patients (6, vii, 8, 9) the disease spread from CN Vii through the auriculotemporal nerve (ATN) to V3 (Figures 1a–b).

Cranial nerves VII, V3 and Auriculotemporal nervus (ATN)

1a-Axial CT from patient 9 showing an abnormal V3 (white arrow), ATN (dashed blackness pointer) and CN 7 (black arrow) on the left side. Normal CN Vii is shown on the right side (black arrowhead).

1b-Centric MRI paradigm from patient 9 showing aberrant ATN (arrows) and subcutaneous mass (dashed arrow). The subcutaneous mass most likely represents growth of affliction along peripheral branches of CN VII.
In two patients (two and 4) with clinical involvement of V2 and CN Vii, involvement of the greater superficial petrosal nerve (GSPN) was demonstrated by MRI. The GSPN most likely immune progression of disease between V2 and CN VII (Figures 2a–b)

Multiple cranial nerves involvement in one patient (patient 2)

2a-Tumor involving the Pterygopalatine ganglion (of CN V) in the Pterygopalatine fossa (black arrowhead), Pterygoid culvert (small arrows), Greater superficial petrosal nerve (GSPN, black pointer) and CN VII (white arrow) on axial MRI image. The GSPN inside the Pterygoid canal is termed "nerve of pterygoid canal".

Involvement of subcutaneous tissue in V2 distribution as a result of antegrade tomor progression is shown as well (white arrowheads).

2b-Abnormal expansion and destruction of the Pterygoid culvert is shown by axial CT (arrowheads). The normal right canal is indicated (arrows).

2c- Aberrant V2 at the cavernous sinus on coronal MRI paradigm (arrow).

second-Abnormal V3 on axial MRI image (arrowheads). The normal right V3 is indicated for comparing (pointer).

2e-Involvement of the lacrimal co-operative of V1 on coronal MRI epitome (arrow).

2f-MRI prototype dated ten months after epitome 2e, showing extensive orbital involvement on axial MRI image.
I patient (patient 1) presented with involvement of peripheral branches of both CN V and CN 7 without evidence for interest of major communicating nerves. Subsequently tumor involvement progressed proximally forth these nerves to the base of skull.
In 4 patients (2, iii, 4, vii) the illness spread from a major branch of CN V to involve additional CN Five branches, most likely through the cavernous sinus (Figures 2c–e).
In four patients (2, iii, four, and 5) affliction spread through V1 or V2 to the orbit (Figures 2e–f). In three of these patients extraocular motor nerves (EOMN; i.due east. CN III, 4 and Half dozen) were secondarily involved either through involvement of the orbital noon or through involvement of the cavernous sinus.
In ii patients (ii and 9) concentric growth of tumor forth peripheral nerve branches was noted (Figures 1b, 2a, 2f), likely due to antegrade illness progression.

Utility of imaging studies

Eleven of 12 patients were evaluated with MRI before therapy (excluding patient 8). In all cases, clinical signs or symptoms prompted an MRI and preceded the radiological evaluation. In just one patient (patient vi) was the MRI negative despite clinical symptoms of, partial, unilateral facial palsy.. Nevertheless, six months later MRI showed involvement of V3, ATN and CN VII.

MRI established the diagnosis of CPNI in six patients, showed progression of disease along nerves in three asymptomatic patients, and revealed the full extent of affliction and was useful for treatment planning in six cases with CPNI.

Treatment

Surgical interventions

In 10 cases multiple and all-encompassing surgical procedures were performed for the primary skin tumor. Parotidectomy was performed in five cases, and resection of facial bones was performed in five cases (temporal, zygomatic or nasal bone). Multiple local recurrences were documented in seven cases and Mohs' surgery was adequate for removal of the skin tumor in only one instance.

Resection of branches or the main torso of CN VII was performed in four cases (patients ii, half dozen, 7, and 8). Patient v underwent resection of the supraorbital nerve (SON) through the orbital apex.

RT to the primary skin tumor

Five patients received a course of adjuvant electron beam RT to the primary tumor bed in the skin. The median RT dose in these cases was 60 Gy (range 45–64 Gy).

RT to involved nerves

Excluding the first course of RT in patient one, all RT courses for CPNI were performed at our department. The intention of therapy varied (Table one): adjuvant treatment after resection of a nerve, definitive treatment for gross disease or palliation of symptoms. Four patients were treated twice with RT for CPNI, to adjacent, mostly non-overlapping sites. In case 11b elective RT to an uninvolved nerve (CN Seven) was delivered along with definitive RT to an auricular tumor.

In vii RT courses the skin was treated along with the nerve. RT to the peel was omitted in the other cases that did not have pare recurrence and had undergone previous RT to the skin.

In total, fourteen courses of conformal RT for CPNI were delivered, vii of which constituted of IMRT. Whatsoever gross abnormality (based on imaging findings) was defined equally gross tumor volume (GTV). Microscopically involved nerves were defined as high risk clinical target volume (CTV). The CTVs always included the uninvolved portion of the involved nervus beyond the GTV through the base of operations of skull (typically, the cavernous sinus for involvement of CN Five, and the stylomastoid foramen and the inner ear for interest of CN VII) (Figure 3). However, elective RT to uninvolved fretfulness was delivered only in case 11B. The pare target included GTV or resected tumor bed with wide margins.

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Examples for clinical target book (CTV) depiction (fretfulness at risk are shown in yellow, CTVs in red)

3a-CTV encompassing the supraorbital nerve (V1) which courses in the roof of the orbit (superior to the superior rectus musculus), major branches of V1, the skin innervated past V1 and the cavernous sinus.

3b-CTV encompassing the infraorbital nerve (V2) in the infraorbital canal, the skin innervated past V2 and the cavernous sinus

3c, d-CTV encompassing preauricular pare, CN 7, the Auriculotemporal nerve (ATN), V3 and cavernous sinus. The book named "cochlea" (3c) contains both a target (CN 7), and the organ at risk. The course of the Greater superficial petrosal nervus (GSPN) is indicated by broken line.

In half dozen cases radiation fields included the regional lymph nodes in the neck. The median dose of RT to neural GTVs in definitive cases was 68 Gy (range 66–70 Gy). The dose of RT to neural CTVs ranged betwixt 50 Gy and 66 Gy. In ii palliative cases doses of 40–50 Gy were prescribed to neural GTVs. In ix cases RT was combined with chemotherapy (Carboplatin-three patients, Carboplatin+Pactitaxel-ii patients, Docetaxel-one patient) or Cetuximab (iii patients).

Treatment results and patterns of failure (Table 1)

5 patients who initially received a class of adjuvant electron beam RT to the skin only, ultimately experienced affliction recurrence, which involved CPNI in all cases; in two patients, skin recurrence was as well observed.

8 patients had disease recurrence following RT for CPNI in face-to-face, previously uninvolved fretfulness. This was the master pattern of failure in v cases; in two patients neural progression was combined with pare involvement and in i patient an in-field neural failure was also observed. No nodal or distant failure was observed in whatsoever patient.

Overall outcome

Patient 10 declined continuation of RT later 12.5 Gy (in the second RT grade) and died one calendar month later. Treatment interruption for two days, was necessary in patient two, due to nausea, airsickness and dehydration, afterward a dose of 16 Gy, The other patients completed their handling without whatsoever suspension or any prohibitive acute toxicity.

Patients 3 and 4 were treated with RT to the orbit. In patient 3 the irradiated centre was blind prior to the treatment due to retinal detachment, and patient iv lost vision in the irradiated centre 14 months after completion of RT. This patient had extensive orbital disease and the mean dose to the optic nervus was 68 Gy. We did non notice any other major late side effects. The median progression free survival of patients receiving RT for CPNI was 5 months and the median overall survival was sixty months.

Give-and-take

The patterns of illness progression and treatment failure observed in this series prompt discussion on several fundamental issues pertinent to target definition in HNCSCC with PNI:

Inclusion of uninvolved nerves in the CTV for adjuvant treatment
1. in patients with MPNI
2. in patients with CPNI
Extent of the CTV for an involved CN
Optimization of RT planning.

1A) Inclusion of uninvolved fretfulness in the CTV for adjuvant treatment in patients with MPNI

While extensive RT is obviously justified in patients with CPNI, elective CN RT (ECNR) is not common practice in cases of MPNI. We encountered five patients who were treated with adjuvant RT to the skin only for MPNI. They all progressed to CPNI and salve RT was unsuccessful; indeed, even as primary handling, RT for CPNI was associated with low rates of local control in our series, similar to reports by others ⁷ ^, ^viii. Nevertheless, this series includes patients who were referred to a tertiary middle because their disease was exceptionally aggressive or due to CN interest. In add-on, three patients were under immunosuppressive treatment. Therefore, the disease course in the patients included in this serial does non necessarily represent the natural history of all cases with MPNI.

Mendenhal et. al. published the largest series of RT for HNCSCC with PNI and proposed criteria for inclusion of fretfulness in the target in patients with MPNI ⁱⁱ ^, ⁹. They recommend ECNR in cases with extensive MPNI, involved surgical margins, or involvement of named nervus branch. Mendenhall et. al. suggested that the target should include the involved nervus with a margin of several centimeters in cases with all-encompassing MPNI, while in cases with positive margins or involvement of a named nerve branch, the entire form of the nerve to the base of operations of skull would be included.

In some cases, the involved nerve is not identified during surgery. Based on patterns of disease spread establish in this study and in other series ⁸ ^, ¹⁰ ^, ¹¹, Preauricular tumors (i.e. lateral to the lateral canthus) are likely to involve CN VII offset, and tumors in the mid-face (i.e. medial to the lateral canthus) are likely to involve CN V first; nevertheless, both CN 5 and CN VII are e'er at adventure, and the CTV should be customized to account for the individual gamble for each nerve.

1B) Inclusion of uninvolved nerves in the CTV for adjuvant treatment in patients with CPNI

A tumor with proven involvement of one nerve is probable to involve additional fretfulness. We encountered several patterns of spread which correlate with those described in the literature:

The major nerves innervating facial skin and musculature

4a. Facial skin regions co-ordinate to distribution of the various sensory nerves. Annotation that skin tumors at whatever facial site tin can spread via both the respective sensory nerve and also via cranial nervus VII if the underlying muscle is invaded past tumor.

4b. Diagram of CN 5 and 7 and their connections.

Notation the Auriculotemporal nerve (ATN) and Greater superficial petrosal nerve (GSPN) connecting CN VII with V3 and V2, respectively, allowing tumor spread betwixt these nerves.

In this study involvement of both CN V and VII was highly prevalent and was present in 11 of twelve cases.

Three different mechanisms may account for this blueprint of disease progression:

Contained risk due to dual innervation of facial skin and musculature by CN 5 and VII, respectively.
Communications between terminal branches of CN V and CN Vii.

Ii major fretfulness connect CN V and 7: ATN ⁵ ^, ¹², which connects V3 with CN Vii as information technology exits through the stylomastoid foramen, and the GSPN ⁵ ^, ¹³, connecting the geniculate ganglion of CN VII and the pterygopalatine ganglion of V2 (Figure 4b). The ATN is peripheral, while the GSPN is intracranial; therefore, the ATN may be involved earlier in the course of disease, when curative handling is more than likely.

Our experience as well as others' ⁸ ^, ¹⁰ ^, ¹¹ ^, ¹⁷ confirms that all three mechanisms play a part in the natural history of HNCSCC with CPNI. Therefore, for tumors involving CN VII, the ATN and V3 are at risk and for tumors involving V2 the GSPN and CN VII are at risk.

Due to the take chances of direct involvement of both CN V and Seven by the primary tumor (as in patient 1), the branches of these nerves that are distributed to the primary tumor are always at risk and should be included in the CTV.

Multiple branches of CN V

In our study multiple branches of CN 5 were involved in v patients.

The underlying mechanisms are similar to those described above: straight interest of more than than a single trunk, or spread between two trunks through either peripheral or major nerve communications ¹⁴. The unabridged CN V might be affected secondary to involvement of the cavernous sinus followed by antegrade extension (Effigy 4b). Therefore, for tumors involving V1, 2, or iii, the other branches of CN V are at risk.

CN 5 and EOMN

In our report iii patients had CN V and EOMN involvement.

Disease involving V1 or V2 can enter the orbit and subsequently progress to involve CN III, Four and VI ⁸ ^, ¹⁰ ^, ¹¹ ^, ¹⁵ ^– ¹⁷, resulting in orbital-noon or clangorous sinus syndrome. This syndrome manifests as ophthalmoplegia, ptosis, pain, and visual loss in advanced cases. Therefore, for tumors involving V1 or V2, EOMN are at risk.

A literature search was conducted for series of HNCSCC and PNI which report the rate of CN involvement. The results are summarized in Table iii. These information likely underestimate the truthful incidence of CN involvement due to their retrospective nature and lack of accurate imaging in some series; however, they are consequent with the patterns observed in our study.

Table 3

Literature summary: CN involvement of patients with HNCSCC and CPNI

Series	Total number of patients	Involved nerves	5+VII involvement
Cottel et. al.²⁴	fourteen	V1-6 V2-4 Auriculotemporal nerve-3 VII-ane Greater occipital nerve-1 III, 4 and 6-1^*	2^†
Garcia-Serra et. al.^four	76	VII-23+7^* V1-ten V2-34+4^* V3-11+10^* II-one^* III-4^* IV-3^* Half-dozen-vii^*	At presentation-five% Secondarily-20%^†
Catalano et. al.²⁵	7	VII-7 V3-3 V2-ii Iii, IV, VI-1	4 (57%)
McNab et. al.⁸ ^†† ^§	21	VII-14 5-xx CN Three, 4 or Six-14	14 (67%)
Clouston et. al.¹⁰ ^††	5	V-5 7-5 III, Iv or Six-5	5 (100%)
Morris et. al.¹¹	26	Seven-15 V-17 Greater auricular nerve-4 3-2	Non reported
Ballantyne et. al.¹⁴	26	V-19 VII-fourteen Greater auricular nervus-3 III, IV, Half dozen Eight-2^*	eleven (42%)
Bowyer et. al.⁶	17	V1-12 V2-4 III, IV and Half-dozen-10 Seven-5 II-4	4 (24%)
Valenzuela et. al.¹⁷ ^†† ^§	8	V1-7 V2-iii VII-v CN III, 4 or Six-4^*	4 (50%)
Current series	12	V-xi VII-11 CN Three, IV and 6-3	10 (92%)

two) Figure 3 shows the extent of the CTV for an involved CN based on patterns of failure.

These volumes reflect our clinical practise, though, elective handling to cranial nerves has get our policy simply recently, post-obit this analysis of patterns of failure.

The patterns of failure presented in Table 2 illustrate the fact that the entire CN network, from the skin to the brainstem, is one anatomical compartment without internal barriers. As a event, disease can progress in antegrade or retrograde style, involve peripheral nerve branches, "resurface" in subcutaneous tissue, and progress to additional nerves through communicating branches. The CTVs should account for all these possibilities past including:

The portion of the nerve proximal to the gross disease:
○ For V1-3, the form of the affected nerve to the cavernous sinus (Figure 3a, b).
○ For CN Seven, the course of the nerve to the encephalon stalk (Figure 3c, d).
A portion of the nerve distal to the gross disease.
The pare innervated past the diseased nerve, with the highest take a chance being at the primary tumor site.
The compartment in which the nervus is embedded and to which it gives branches (e.thou., the orbit for V1 and V2, the masticator space for V3, and the parotid gland for CN VII)

These targets would generally be defined as high hazard CTVs, unless they are remote from the gross affliction.

iii) Optimization of RT planning

MRI has a fundamental role both for clinical evaluation besides every bit for RT planning in HNCSCC with PNI. In the electric current series, the sensitivity of MRI was 89% (C.I. 52–99%), and the reported sensitivity and specificity of MRI in the literature are 95–100% and 95–85% respectively ^xviii ^, ¹⁹. However, MRI may underestimate disease extent, accounting for reported accuracy of only 63% ¹⁸. In this series MRI showed disease progression in three asymptomatic cases. In some other series MRI showed CN involvement in two of 11 asymptomatic patients²⁰. MRI is therefore recommended to assess and ascertain the extent of the GTV for cases with CPNI or high gamble MPNI.

Organs at risk in cases of CPNI may non simply be adjacent to the targets, but may actually be contained within the target (Effigy 3c). Our current approach is to define the targets and prescribe doses based on the guidelines outlined below. We assign private dose limits to the organs at risk which may replace target dose goals such that "common cold areas" are produced effectually organs at risk in the target. For example, the dose to the cochlea is limited to 45 Gy in cases of adjuvant RT for CN Seven²¹ and the dose to the retina and optic nervus/chiasm is kept below 45 Gy and 60 Gy, respectively, when the cavernous sinus or orbit are part of the CTV²² ^, ²³. Higher dose limits are acceptable if these structures are involved with gross illness. In all cases, an endeavour should exist fabricated to reduce the dose to the contralateral vision pathways every bit much as possible. An expansion of 3mm is used for the critical organs at risk to account for fix-up uncertainty, and daily imaging and set-up correction is expert to ensure right gear up-upward.

Differential doses are prescribed to GTV, high run a risk CTV and low adventure CTV (typically, 70Gy, lx–63 Gy, and 54–56 Gy, all in 35 fractions, at 2.0 Gy, 1.7–1.8 Gy, and 1.6 Gy per fraction, respectively). Combination of RT with chemotherapy or targeted therapies may exist considered in cases with CPNI. These issues may be addressed in a similar manner as in cases of mucosal HNSCC; however, no like information from randomized studies are available for HNCSCC.

Summary

In order to optimize local command with conformal RT or IMRT for HNCSCC with PNI, the diverse routes of disease spread have to be accounted for in the procedure of RT planning. Although rarely axiomatic at presentation, eventual involvement of multiple CNs is mutual and may be the cause of local failure. Information technology usually follows several anticipated patterns depending on the chief tumor site. These patterns, described in the current paper, can serve for rational decision-making virtually the targets, especially the CTVs, in cases of PNI. Future studies are needed to improve risk assessment in cases with MPNI and to explore the safe and potential do good of combining RT with chemotherapy or targeted agents.

Acknowledgments

Dr. Gluck was supported by the Trico Foundation.

Footnotes

Conflict of involvement: None

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702210/

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