ARTICLE
Auteur(s) : Massimo CACCIALANZA1, Roberta
PICCINNO1, Devis MORETTI1, Maurizio
ROZZA2
1 Department of Photoradiotherapy, Institute of
Dermatological Sciences of the University, Ospedale Maggiore,
IRCCS, Via Pace 9, 20122 Milan, Italy.
2 Department of Health Physics, Ospedale Maggiore,
IRCCS, Via Pace 9, 20122 Milan, Italy
Reprints: M. Caccialanza Fax: (+ 39) 02 503 20779
E‐mail: scienze.dermatologicheunimi.it
Article accepted on 3\7\2003
Key words: The head and neck are the sites most
affected by basal and squamous cell carcinomas of the skin,
accounting for about 70% of all cases [1‐3]. The skin overlying
nose cartilage is a particularly frequent localization of skin
carcinomas: in fact it is the site of about 25% of all carcinomas
occurring on the head and neck [4]. For a long time this skin area
has been considered a localization where the radiotherapy treatment
finds one of its major indications [5‐8]. Such therapy may be
performed with high energy radiation to treat lesions involving
bone and\or cartilage, while carcinomas localized at the nasal
vestibule are particularly suitable for treatment with interstitial
curietherapy methods. On the other hand, lesions exclusively
involving the skin overlying cartilage may be treated by
superficial radiotherapy. After having acquired additional
experience through a previous study of our group [9] on the latter
modality of radiation treatment, we considered it to be of
practical interest to provide a further evaluation of the
therapeutic effectiveness and "toxicity" of dermatologic
radiotherapy in the treatment of skin carcinomas overlying the
cartilage of the nose.
Materials and methods
Three hundred and eighty‐nine (11.36%) out of 3423 patients
affected by primary malignant epithelial skin neoplasms and treated
with radiotherapy in the period 1972‐2002 showed a localization of
the disease, histopathologically assessed following an incisional
biopsy, at the skin overlying the cartilage of the nose. A
retrospective study was performed on this series. The generalities
of the patients studied and the modalities of the treatment are
listed in Tables I‐IV. In spite of the well‐known
recommendation to avoid radiotherapy under the age of 50, a patient
aged 37 has been included in our series: due to mental
retardation it was not possible to perform a surgical excision.
Fifty‐four patients had undergone multiple different treatments
prior to radiotherapy and had relapsed (Table III) . In all cases, where an extension
of the neoplasm to the tissues underlying the skin was suspected,
an otorhinolaryngologic visit and a craniofacial CT scan were
performed.
Table I. Case list generalities
|
|
No |
| Cases |
|
389 |
| Sex |
Males |
197 (52.2%) |
|
Females |
190 (48.8%) |
| Age |
Mean: 73.8 years |
|
|
Range: 37‐96 years |
|
| Lesions |
|
405** |
| TNM [10] |
T1N0M0 ( 2 cm) |
362 (89.4%) |
|
T2N0M0 (> 2 < 5 cm) |
29 (7.2%) |
|
T3N0M0 (> 5 cm) |
13 (3.2%) |
|
T4N0M0 (involving the underlying tissues) |
1 (0.2%) |
| Clinical variety |
Nodular |
137 |
|
Nodular‐ulcerative |
112 |
|
Flat |
80 |
|
Ulcerative |
48 |
|
Flat‐ulcerative |
21 |
|
Morphea‐type |
7 |
| Histopathology |
Basal cell |
393 (97%) |
|
Squamous cell |
12 (3%) |
** 16 patients with 2 lesions
. Table II. Location of irradiated lesions
|
No |
| Ala nasi |
158 |
| Tip |
120 |
| Dorsum |
80 |
| Tip and dorsum |
21 |
| Ala and dorsum |
16 |
| Tip and ala nasi |
10 |
| Total |
405 |
. Table III. Lesions relapsed after previous
treatments
| Treatment |
No |
| Surgery |
17 |
| Cryotherapy |
11 |
| Electrodesiccation |
11 |
| Lasertherapy |
5 |
| 5‐Fluorouracil ointment |
4 |
| Retinoid cream |
1 |
| Cryotherapy + Surgery |
4 |
| Cryotherapy + Lasertherapy |
1 |
| Total |
54 (13.3%) |
. Table IV. Technical data of radiotherapy
|
CRT |
HDRT + CRT |
| Number of lesions |
403 |
2 |
| Voltage |
55‐60 kV |
80‐120 kV\55 kV |
| Amperage |
4‐6 mA |
6 mA |
| Filter |
‐‐ |
2 mm Al |
| HVD |
2‐12 mm |
25‐30 mm\2‐12 mm |
| Fraction |
2 times per week |
5 times per week\2 times per week |
| Dose per fraction |
5 Gy |
2 Gy\5 Gy |
| Total dose |
40‐85 Gy |
50‐60 Gy |
CRT ∓ Contact x‐Ray Therapy
HDRT ∓ Half‐Deep x‐Ray Therapy
kV ∓ kiloVolt
mA ∓ milliAmpère
HVD ∓ Half‐Value‐Depth (tissue layer reducing the
surface dose to 50%)
Gy ∓ Gray
.
In two extended lesions contact x‐ray therapy (CRT) was preceded
by half‐deep x‐ray therapy (HDRT) (Table
IV), performed by utilizing a luminous centralizer
connected to the head of the source of ionizing radiation. The
remaining twelve lesions which were larger than 5 cm (T3‐T4
N0M0) were treated by means of CRT with juxtaposed fields. The
quality of radiation and the size of irradiation fields were chosen
on the basis of the size, site and degree of infiltration of the
neoplasm. The size of irradiation fields was always wide enough to
include an adequate skin margin (0.5‐1 cm) around the
neoplastic lesions. In seven morphea‐type basal cell lesions
treated, the irradiation field size always included a skin margin
of 1.5 cm around the neoplastic lesions, due to the difficulty
in obtaining a correct evaluation of the margin to be irradiated,
characteristic of this type of carcinoma [11]. The total doses
administered are listed in Table V.
In the patients treated at alae nasi, lead rubber (equivalent to
1 mm Pb) shields were inserted into the nostril, in order to
protect the cartilage of the septum. When HDRT was used
(2 patients) the critical organs near the irradiation fields
were protected by lead rubber shields (equivalent to 4 mm Pb).
The follow‐up was planned so as to perform a first control one
month from the end of the treatment, then the patients were
controlled every sixth months for 5 years and once a year
afterwards.Table V. Total dose administered
|
No of lesions |
Total dose (Gy) |
No of lesions |
| CRT |
403 |
40 |
1 |
|
|
45 |
1 |
|
|
50 |
9 |
|
|
55 |
312 |
|
|
60 |
78 |
|
|
75 |
1 |
|
|
85 |
1 |
| HDRT + CRT |
2 |
55 + 20 |
1 |
|
|
60 + 20 |
1 |
.
The data were processed by means of Excel 6.0 software
(Microsoft Corporation, 2001). The actuarial cure‐rate was
evaluated according to the life‐table method [12].
The statistical analysis of some data was performed using the
chi‐square test, p < 0.05 was considered
statistically significative.
Results
The mean follow‐up time was 31.7 months (range 1 to
348 months). Table VI summarizes
the therapeutic results. Complete remission was obtained in
381 lesions (94.1%), evaluated at the first visit one month
after the end of treatment. The cure‐rate is reported in Figure 1. In
particular, the five‐year cure‐rate was 88.6%. Twenty‐four lesions
(5.9%) relapsed after a time period ranging from 2 to
54 months from the end of treatment (mean 17.8 months)
(Table VII). Even considering the small
size of the sample, a statistically significant relationship was
observed between the risk of relapse and both the administered
doses (p < 0.001) and the size of the lesions
(p ∓ 0.001). Therefore, the greater the size of
the lesions and the lower the doses of radiotherapy administered,
the higher is the risk of relapse. Of the 24 patients
presenting a relapse, 3 were lost to follow‐up,
2 underwent surgical excision and then were lost to follow‐up,
while the remaining 19 were treated with one or more courses
of application of 5‐fluorouracil ointment. In 11 cases such
therapy resulted in a complete remission of the neoplasm, in
6 cases in a control of the disease and in 2 cases was
not effective. One of these two patients underwent surgical
excision and then was lost to follow‐up. The cosmetic result (Table VI) was considered as « good »
in the cases characterized by no visible radiation injury, as
« acceptable » in those characterized by mild skin
atrophy and\or mild dyschromia, and as « not acceptable »
in those with severe skin atrophy and\or marked dyschromia and
presence of numerous telangiectasias. Due to the inhomogeneous
distribution of the sample it was not possible to use the
chi‐square test in order to investigate a possible relationship
between cosmetic result and dose and between cosmetic result and
size of the lesions.
Table VI. Results of radiotherapy
|
No of lesions |
% |
| Remission |
381 |
|
94.1 |
Recurrence
(11 central, 13 marginal) |
24 |
|
5.9 |
| Mean follow‐up |
31.7 months (range:
1‐348 months) |
| Cure‐rate (five‐years) |
|
|
88.6 |
| Cosmetic results |
Good |
289 |
75.8 |
|
Acceptable |
82 |
21.5 |
|
Not acceptable |
9 |
2.4 |
|
Not evaluable |
1 |
0.3 |
Complications\
sequelae |
0 |
|
0 |
. Table VII. Lesions relapsed after
radiotherapy
|
|
No |
Total dose (Gy) and No |
| Histopathology |
Basal cell (1 morphea type) carcinoma |
23 |
|
|
Squamous cell carcinoma |
1 |
|
| TNM |
T1N0M0 |
19 |
50 → 1 |
|
|
|
55 → 16 |
|
|
|
60 → 2 |
|
T2N0M0 |
3 |
55 → 2* |
|
|
|
60 → 1 |
|
T3N0M0 |
1 |
55 → 1 |
|
T4N0M0 |
1 |
60 → 1 |
| Location |
Tip |
9 |
|
|
Ala |
6 |
|
|
Dorsum |
4 |
|
|
Tip and dorsum |
5 |
|
| Lesions relapsed after previous non‐radiological
treatments |
|
5 |
|
* 1 morphea‐type
. .
So far, no complications nor sequelae to the radiological
treatment have been observed, except in the 9 lesions where
the cosmetic result, evaluated as not acceptable, may be considered
as an aspect of radiation damage, to be followed in time (Table VI).
Discussion
The carcinomas of skin overlying nose cartilage are a group of
neoplasms endowed with peculiar characteristics from the
therapeutic point of view. The nose is a localization influencing
the appearance of the patient, having a very high cosmetic
importance besides a functional one. Furthermore, if we consider
that this area is characterized by a recurrence rate for skin
carcinomas higher than in any other body site [13], it is easy to
understand the need to identify treatments able to combine
therapeutic effectiveness with favourable cosmetic and functional
results. The therapeutic option considered should also be devoid of
side effects and of acute and chronic complications as much as
possible. Clinical studies on therapeutic modalities of skin
carcinomas should include histopathologic examination, staging
according to a well‐known international classification, and be
performed on a consistent number of patients with an adequate
follow‐up. The series of patients reported here satisfies these
conditions. Among the several available therapies, cryotherapy,
electrodesiccation and topical chemotherapy are less frequently
employed and restricted to treating small sized and superficial
lesions, since they are burdened with a high rate of relapse and
often give unsatisfactory cosmetic results [14, 15]. More recently,
new treatment modalities have become available, such as
intralesional alpha‐interferon administration, photodynamic therapy
and lasertherapy: up to now, however, the few case series reported
in the literature do not allow us to fully evaluate their true
effectiveness [16,17], mostly due to the lack of an adequate
follow‐up. Lately some reports about imiquimod cream in the
treatment of BCC have been published: however they describe
clinical series regarding small\medium‐sized lesions (T1‐2N0M0) and
lacking follow‐up [18]. Surgery, considered by many the first
choice treatment, is often difficult to perform even in the
medium‐small tumours, because the skin is closely adherent to the
underlying cartilage and therefore lacks sufficient elasticity.
Furthermore, in the more widespread forms extensive surgery is
necessary, with resection of a large portion of healthy skin, in
order to obtain adequate resection margins. Moreover, complex
plastic surgery becomes necessary and this does not always ensure
functional and cosmetic satisfaction. Therefore, the skin overlying
nasal cartilage represents an elective localization for
radiotherapy. Technically indicated in the treatment of these
neoplasms, radiotherapy has always been disadvantaged by the fear
of damaging the tissues underlying the skin. However, the
improvement of radiotherapy techniques and radiobiology knowledge
has enabled us to overcome this problem: in particular it has been
assessed that the absorption of ionizing radiation in cartilage is
superimposable to that in soft tissues [19]. The radiotherapy
technique most suitable to treat basal and squamous cell carcinomas
exclusively involving the skin overlying nasal cartilages is
kilovoltage radiotherapy performed by means of skin
disease‐dedicated machines: this method allows a high concentration
of the dose on the surface, a good collimation of ionizing
radiation beam and a rapid fall of the dose under the target
volume.
The series of patients here reported is characterized by a
significant percentage of neoplasms relapsing after previous
non‐radiological treatments (13.3%) and by a non‐negligible amount
of extensive (T2‐3‐4 N0M0) lesions treated (10.6%). Both these
groups of neoplasms are considered at risk for a higher resistance
to every available therapy [6, 17, 20]. The results obtained
following our thirty‐year experience (five‐year cure‐rate from the
end of radiotherapy 88.6%, cosmetic results as good or acceptable in 96.13% of the treated lesions, lack of
complications and\or sequelae) are in the mean of the data
published in the literature [21‐26] and confirm that radiotherapy
performed with machines dedicated to skin diseases may be
considered as one of the preferential therapeutic modalities in the
treatment of skin carcinomas overlying nose cartilage. Besides, it
is particularly relevant to observe that, with a very long
follow‐up period (up to 348 months) no stochastic damages have
appeared: such data confirm that radiotherapy for skin carcinomas
is a very safe treatment. Further evidence about the suitability of
the choice of radiotherapy in the treatment of skin carcinomas
overlying the nasal cartilage comes from a recent randomized trial
carried out to compare the cosmetic results of surgery and those
obtained with radiotherapy in the treatment of facial basal cell
carcinoma: it has been assessed that, after 4 years from
completion, both treatments gave similar results at the level of
the nose skin, while the surgical results were better at all the
other sites [27].
Finally radiotherapy, for its characteristics (painlessness,
possibility to be performed on an outpatient basis), is a first
line treatment in patients who can not undergo surgery for age,
general health conditions, and so on.
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