8

Lip Cancer
Alain Gerbaulet, Erik Van Limbergen

1 Introduction
The vermilion of the lip forms a transition zone between skin and oral mucosa and therefore the risk
for cancer is related both to sun exposure and classical etiological factors for oral cancer such as
tobacco, alcohol and bad oral hygiene.

Farm labourers and fishermen have a higher risk of lip cancer, as they are likely to be exposed to
these risk factors.

2 Anatomical Topography
Histologically the lip can be divided in three different parts. The cutaneous lip (see chapter on skin
cancers) goes over the vermilion or dry mucosa of the lip, which forms a transition zone between the
skin and the wet oral mucosa.

Its lateral limits are about 1cm from the lip commissures: the upper limits are the naso-labial groove
at the skin and the gingivo-labial groove at the mucosa side; the lower limits are the mento-labial and
the lower gingivo-labial groove.

Its lymphatic drainage goes to the sub-mental, sub-mandibulary and sub-digastric lymph nodes. The
submandibular nodes are the most frequently involved.

All patients affected with tumours reaching the median line are at high risk for bilateral nodal
involvement.

3 Pathology
Most lip cancers are squamous cell cancers (90%). The remaining 10% are basal cell cancer
(starting from the cutaneous area). Sarcomas, cylindromas, melanomas are very rare.

Pre-cancerous conditions, such as actinic cheilitis, leucoplakia, Bowen’s disease, are frequently
associated. They often constitute a diagnostic and an additional therapeutic problem. In general
these associated lesions can be adequately treated by radiotherapy but form rather a
contraindication to limited surgery.

4 Work Up
The mean age of a patient suffering from lip cancer is over 65 years; patients are often in poor
general condition, contraindicating major surgical excision and flap reconstruction.

An accurate medical examination should always include a systematic examination of the head-and-
neck region, of the skin and teeth as well as X-rays of chest and mandible when indicated.
228 Lip Cancer

It is mandatory to carefully inspect and palpate the tumour area and the whole affected lip, the other
lip and the commissural areas. The tumour itself may be exophytic, ulcerated, or infiltrating. These
three forms can sometimes co-exist.

The size (in mm) and site of the tumour: (cutaneous lip, vermilion, wet mucosa), invasion of lip
muscles or commissural invasion should be carefully assessed and noted. Any infiltration of the wet
mucosa significantly increases the risk of nodal metastases.

Lip cancers are often poorly defined. Associated lesions are far from rare and should actively be
sought for and noted as well. Detailed drawings or photographs will help to document the exact size
and localisation. From every tumour and any suspected extension adequate biopsies should be
taken.

Lymph node involvement is rare but can be frequently bilateral. A bi-digital palpation with a finger
inside the mouth is necessary to better estimate the nature of submandibular lymph nodes. In case of
clinical doubt, fine-needle aspiration is a simple procedure to assess involvement.Lymphnodes have
been reported in 2% of T1, 6% of T2 and 15- 30% of T3 cases (8). Lymphnode involvement is more
frequent when there is tumour extension to the wet mucosa (6,7).

Tumour must be staged, according to the TNM staging system. (See appendix)

5 Indications, Contra-indications
Brachytherapy is indicated in over 90% of lip cancers.

A simple surgical wedge excision is only indicated for very superficial, small tumours less than 0.5
cm in their major axis. However the local recurrence rate, varying between 10 and 30% according to
different authors should be used (1,6,9) in any case suggests systematic postoperative
brachytherapy.

Larger tumours (over 5 cm in their major axis) are treated by external beam radiation followed by
brachytherapy, or surgical excision followed by reconstruction surgery with an Abbe- Estlander lip
flap rotation or derived techniques. Tumours invading adjacent bone usually require surgery if
feasible.

6 Target Volume
The clinical target volume includes all visible and palpable tumour extensions with a safety margin of
5 - 10 mm according to the different directions. Because there is little movement of interstitial
implanted sources when adequately fixed with templates or plastic tubes, the PTV usually
corresponds very closely to the CTV.

7 Technique
Over 90% of cases can be treated by brachytherapy alone (6). It is nowadays classically performed
with Iridium192, applied in small source carriers. These are usually hypodermic needles but also guide
needles, classic nylon tubes, silk threads, small vascular catheters, guide gutters, or a combination of
more of these afterloading techniques in the same patient.

Whenever possible a custom made protection device should be prepared to shield the upper lip and
 Lip Cancer 229

the lower gum (fig 8.1). The protector consists of a 2mm lead shield placed between both lips and the
mandible, contained in an acrylic mouthpiece. This reduces the dose to the upper lip and lower gum
by a factor of two. It must be made by an experienced colleague in the stomatology or dental
department and tested for comfort befor the patient starts brachytherapy.

To make exact dosimetry possible an identical dummy protector without lead shielding or removable
lead plate can be made and used for dosimetry. However this procedure with a dummy protector is
not so important as for intra-oral implants where the presence of the protector really disturbs the
position of the implanted nylon tubes.

Fig 8.1A: Acrylic custom made protection Fig 8.1B: X-Ray of implant with protection in
device containing a 2mm lead plate for shielding place.
upper lip and lower gum during brachytherapy.

7.1 Hypodermic needles

These are hollow, bevelled needles with small outer diameter (0.8mm) and variable length (4 to 8
cm), open at both ends. They cause little trauma and can be directly inserted in the tissues. This
technique is the optimal technique for lip carcinoma (Fig 8.2).

Fig 8.2: Typical hypodermic needle implant of the lip in an equilateral triangular configuration with
protection device in place. Needles have been afterloaded with Iridium 192 wires (2A). X-Ray control
(2B).

The rigid fixed steel and template system avoids collapse of the sources due to the elasticity of the
soft tissues.
230 Lip Cancer

Templates with predrilled holes (0.6 mm) in a triangular configuration and with spacing of 10 to 15
mm should be available in the department.

Hypodermic needles can be used in lip tumours of less than 3cm in largest diameter, not involving
the lateral commissurae. The inner diameter is 0.5 mm and can be afterloaded with 0.3mm iridium192
wires.

7.2 Classic plastic tubes

They have a diameter which is larger (1.6 to 1.9mm) than hypodermic needles. They are more
flexible, allowing a better adaptation to round surfaces (Fig 8.3). However it is more difficult to keep
good parallelism between tubes over the whole length of the treated volume Large plastic tubes are
therefore indicated for larger masses, or when the lateral commissurae or cheek are involved.

Their loading has sometimes to be delayed as long as necessary for regression of the post
brachytherapy trauma and oedema.

Fig 8.3: Interstitial implant in three planes :

the deep and middle plane with plastic tubes,
the superficial with hypodermic needles.

7.3 Silk threads

They are seldom used for the brachytherapy of lip cancer, unless it is a very small lesion
preferentially in the upper lip (Fig 8.4). They can be used in the completion of a plastic-tube implant,
or in combination with hypodermic needles. For example when a part of the tumour bulges out of the
implanted area and a sub-optimal dosage is achieved, this can be corrected by an additional silk
thread that can “warm up” the under-treated area.

Fig 8.4: Basal cell cancer of the uppr lip implanted with the silk thread technique (4A)
and cosmetic result two years later (4B).
 Lip Cancer 231

7.4 Small vascular catheters

Their indications for lip cancer are similar to the indications for silk thread and small plastic tubes.

7.5 Guide gutters

Guide gutters are only exceptionally used. They are reserved to treat lesion with limited lateral
commissura involvement.

8 Dosimetry
Orthogonal projection images are taken to register the source positions. Usually computer dose
calculations are done. Mean Central Dose is determined. The prescribed dose to the Minimal Target
Dose usually corresponds to 85% of the MCD (Paris System).

9 Dose, Dose Rate, Fractionation

The prescribed dose is 60- 75 Gy at the 85% reference isodose, at dose rates between 30 to 90
cGy/h. Usually a dose rate at 45 to 80 cGy/h should be aimed at. Therefore, the linear activity of
iridium sources should be in the range of 5.5 to 7.7 cGy/hr linear Air Kerma rate at 1 meter.
Depending on the linear activity and the source spacing and length this will take 4 to 6 days to deliver
the aforementioned dose. A dose of 60-65 Gy for T1 and 65-70 for T2 is advocated. Although doses
up to 70-75 Gy can be given in some large tumours, without unacceptable sequels (6,7) the raise in
cosmetic radiation damage is higher than the gain in local control expected from a dose increase
above 70 Gy (13).

10 Monitoring
Daily control of the position of source carriers and protector device is mandatory. Minor analgesics
may be indicated.

Acute side effects as mucositis ( in the second week) and epidermitis (in the third to fourth week)
can be mild (Fig 8.5A) to severe (Fig 8.5B) and have to be treated symptomatically with topical
applications.

Fig 8.5A: Mild mucositis in a patient with a small (3mm source length) implant and having worn the
protection device. Fig 8.5B: Severe mucositis of both lips and tip of the tongue four weeks after
implant in a patient treated with high dose (75 Gy) without protection device.
232 Lip Cancer

11 Results
Lip cancer is a common malignancy in the head and neck region, and is very often diagnosed at an
early stage. Surgery as well as external radiotherapy, and interstitial implants with radioactive
sources are very successful in treating these lesions. Modern brachytherapy (BRT) with Iridium wires
is a simple and effective treatment modality leading to excellent local control rates and cosmetic and
functional results.

11.1 Local control

Overview of the literature shows local control rates of 90 - 95% at 5 years (table 8.1) for Ir-192
brachytherapy following the Paris system implantation rules. The results are somewhat better in T1
(0% - 5%) five year failure rates than in T2 disease: 2.1% - 8.2% (3 - 6,9,12,14).

Table 8.1: Local control results after interstitial brachytherapy for lip cancer.

Author Cases BT-Dose 5 year (10y )*Local Failure Rates

All T1 T2 T3 T4 PSR

Gerbaulet et al. 316 T1-T4 Ra206 4.2% 0% 2.1% 7.7% 4/6

1978 (6) Ir192
Pigneux et al. 93 Ir192 65-75Gy 4.5% 2.2% 4.3% 5.2% _
1979 (11)
Mazeron et al. 1896 T1-T4 629 Ra206Cs137 10.9% 8.3% 10.8 % 7/12
1983 (8) 1267 Ir192 3.4 % 1.6% 3.4 % 10 % 1/15
192
Cowen et al. 248 Ir 60-81 Gy 4% 3.4% 5.4% 3.7% 6/9
1990 (3)
Orrechia et al. 47 T1-T2 Ir192 60-80 Gy 6.4% 6.4 % _ _
1991 (10)
Van Limbergen 2794 T1-T4 Ir192 40-90Gy 6% 5% 8.2% 19% 0/24 17%
137
1993 (13) PSR Cs 10%* 7.5% 12% 30% 23%
Cerezo et al. 117 XRT 4% 4% 6% _
1993 (2) (+-surgery)
Gerbaulet et al. 231 Ir192 70-85 Gy 5.6% na Na na na
1994 (7)
Beauvois et al. 237 T1-T4 Ir192 65-68 Gy 5% _
1994 (1) 8%*
Farrus et al. 72 T1-T3 Ir192 62-67 Gy 11% 10% 7% 25% _ 13%
1996 (5) PSR
De Visscher 108 T1-T3 Ir192 48-70 Gy 4.6 % 1.1 % 23.5 % 0/2
1996 (4) XRT,EL, photons
Tombulini 57 T1-T3 Ir192 62 Gy 10 % na Na na _
1998 (1)

PSR: post surgical recurrences

 Lip Cancer 233

They seem to be slightly worse with old radium or Cesium needle technique (9), or when Paris
system implantation rules are not followed. In the Barcelona study (5) local recurrences were 1/21
(4.8%) when active source lengths were long enough for covering the PTV and were 7/51 (13.7%)
when source lengths were shorter than prescribed by Paris System rules. Beauvois (1) reported even
that when the entire lip was treated (this was the treatment policy in Nancy after 1985) no
heterolateral lip recurrences were seen.

In the large 1993 GEC-ESTRO brachytherapy for lip cancer study (brachytherapy for lip cancer study
224 recurrences in 2794 patients were noted over a long follow up time (up to over 15 years) with an
annual probability for recurrence rate of less than 1% (13). The local disease free survival probability
(DFS) at 5, 10 and 15 years follow-up were respectively 94%n 90% and 89%. Significant higher local
control rates were seen in lower lip cancers, and worse in commissura lesions (P=0.00001). A highly
significant difference was noted between the local control rates according to T-stage (P=0.00001).
For T1 tumours, the 5, 10 and 15 years DFS were respectively 95%, 91% and 90%; for T2, they were
91%, 89% and 86%; and for T3 in 82%, 78% and 78%. Local control rates were worse in poorly
differentiated tumours: the 5 and 10 year local control rates being 97% and 95% for WHO I lesions,
95% and 80% for WHO II, and 80% and 77% in WHO III lesions. There were no differences in local
control rates for patients treated with combined surgery and brachytherapy versus patients treated
with brachytherapy alone.

Besides T size, the brachytherapy dose delivered is the major predictor for local control. In the GEC-
ESTRO (13) in field recurrences decreased with increasing doses in T1 and T2 lesions (table 2)
excepted in a small subgroup of 38 T2 patients treated at very high doses, 26 of them in the same
institute, suggesting that technical performance might be responsible for the 8 - 11% local failures
rates in the over 80 Gy dose group.

Table 8.2: Dose dependency of local control of lip ca treated with brachytherapy.

GEC-ESTRO 1993 Lip CA study 5 year True Local Failure rate in

function of Dose
T1 T2
n % n %
40-50 Gy 9 44% - -
50-60 Gy 56 5% 29 6.9 %
60-70 Gy 300 2% 189 4%
70-80 Gy 482 3% 255 3.1%
80-90 Gy 70 2.8% 38 8%
> 90 Gy 18 0% 9 11%

Excluding this subgroup the data suggest that 60 - 65 Gy is optimal to treat T1 (2 - 3% local failure at
5 years) and 65 - 70 Gy optimal to treat T2 lesions (3.1-4% local failure rate at 5 years). There was
no obvious influence of brachytherapy dose rates on local tumour control within the range of 20
cGy/hour to 239 cGy/hour.

These local control rates compare favourably with surgical series (6 - 30% local failures) (1,6,8). In
addition, local recurrences can be salvaged in 80 % of cases by surgery (3 - 6, 10 - 12) or
brachytherapy (1,6,9,11) (Table 8.3).
234 Lip Cancer

Table 8.3: Results of salvage treatment for local recurrences of lip cancer after initial
brachytherapy*, or external beam RT**.

Author N N lip rec Salvage treatment Local Salvage Ratio Ultimate

LC
Gerbaulet 316 24 Surgery, salvageBT 14/22 64% 97.4%
1978 (6)
Pigneux 91 4 Surgery, salvageBT 4/4 100% 100%
1979 (11)
Nguyen na 31 Salvage BT 28/31 90% na
1982 (9)
Cowen 1990 (3) 248 18 Surgery 15/18 83 % 98.8%
Orrechia 47 3 Surgery 2/3 66% 98%
1991 (10)
Beauvois 237 12 Surgery, 11/12 91% 99%
1994 (1) Salvage BT
Farrus 72 8 Surgery 7/8 87.5% 98.6%
1996 (5)
De Visscher 108 5 */** Surgery 5/5 100% 100%
1996 (4)
Tombolini 59 6 Surgery 3/6 50% 95%
1998 (11)
Total 111 89/111 80.2%

11.2 Complications

Since the lip is rather radioresistant; severe complications are rare. Superficial necroses occur in
2.8 - 10.1% (3,6,10,13). They heal spontaneously in 70% before six months and require surgery in
less then 5% of cases (3) Lip ulceration depends strongly on total dose and dose rate. In the Gec -
Estro overview (13) there was no incidence of lip ulceration in 0% with doses under 50 Gy, 4.8% for
50 - 60 Gy, 6.3% for 60 - 70 Gy, 7.3% for 70 - 80 Gy, 7.7% for 80 - 100 Gy and in 3/8 patients treated
with doses over 100 Gy. Ulceration also is dose rate dependent since present in 2.5% at dose rates
under 40 cGy/h, in 6% between 40 - 80 cGy /h, 6.9% between 80-120 cGy/h and 15.2% at dose
rates over 120 cGy/h.

Cosmetic outcome is good to excellent in 80%-95% (Fig 6A and 6B) (3,6, 8,13) with usually only mild
depigmentation in 2.5 - 17.3% (3,6,13), teleangiectasia in 15.2% (13), light oedema in 4.4% (3),
dyskeratosis in 4.8% (3) or fibrosis in 8%) (3) .In the GEC-ESTRO review good to excellent
cosmesis was seen in 94.9% of T1, 84.3% of T2, 72.5% of T3 and 60% of T4. Poor outcome was
noted in 1.3% of T1, 4.1% of T2, 10.1% of T3 and 20% of T4 (13).

Lip deformation and retraction is seen in 6% (3) of cases and is seen more frequently after treatment
of larger lesions (3,8,13) and commissura lesions (3,13) (Fig 7); Functional loss due to lip
deformation was noted in the GEC ESTRO overview in 0/126 upper lip, 0.5% of 1199 lower lip, and
in 4.2% of 92 commissura cases (13). Mazeron (8) reported grade 3 cosmetic and functional
sequellae in 1% of 393 T1, in 5% of 363 T2 and 9 % of 78 T3 lesions.
 Lip Cancer 235

Fig 8.6: Squamous cell lip cancer (6A) and cosmetic outcome (6B) five years after 75 Gy LDR
brachytherapy.

Fig 8.7: Bulky lip cancer at the lateral commissura extending in both upper and lower lip (7A) and
cosmetic outcome after 10 years (7B).

Cosmetic outcome has also been related to dose and dose rate. In the GEC-ESTRO study cosmetic
outcome was excellent or good in 96.5% under 50 Gy, 91% between 50 - 70 Gy and 85% for doses
over 70 Gy. In T1 cases (when cosmetic damage due to T size is minimal) bad cosmesis was seen in
0% when dose was lower than 60cGy, 1.5% between 60-80 Gy, and 8.6% over 80 Gy.

12 References

1. Beauvois S, Hoffstetter S, Peiffert D, et al. Brachytherapy for lower lip epidermoid cancer:
tumoral and treatment factors influencing recurrences and complications. Radiother Oncol 1994;
33: 195-203.
2. Cerezo L, Liu FF, Tsang R, et al. Squamous cell carcinoma of the lip, analysis of the Princess
Margaret Hospital experience. Radiother Oncol 1993; 28: 142-7.
3. Cowen D, Thomas L, Richaud P, et al. Cancer des lèvres. Résultas du traitement de 299
patients. Ann Oto-Laryngol 1990; 107: 121-6.
236 Lip Cancer

4. de Visscher JGAM, Grond AJK, Blotke G, et al. Results of radiotherapy for squamous cell
carcinoma of the vermilion border of the lower lip. A retrospective analysis of 108 patients. Oncol
1996; 39: 9-14.
5. Farrús B, Pons F, Sánchez-Reyes A, et al. Quality assurance of interstitial brachytherapy
technique in lip cancer: comparison of actual performance with the Paris System
recommendations. Radiother Oncol 1996; 38: 145-51.
6. Gerbaulet A, Chassagne D, Hayem M, et al. L’épithélioma de la lèvre. Une série de 335 cas. J
Radiol Electrol 1978; 59: 603-10.
7. Gerbaulet A, grande C, Chirat E, et al. Braquiterapia intersticial con iridio 192 en el carcinoma
del labio: analysis de 231 casos tratados en el Institut Gustave Roussy. Oncologia 1994; 17: 45-
9.
8. Mazeron JJ , Richaud P. Compte Rendu de la XVIIIe réunion du Groupe Européen de
Curietherapie. Padova, mai 1981 Sesion consacrée aux cancers de la lèvre. J Eur Radiother
1984 ; 5: 50-56.
9. Nguyen TD, Douchez J, Combes J, de Lafontan B, Daly N, Combes PF. Recidives tumorales
pures de cancers labiaux. Traitement de ratrappage par curiethérapie interstitielle. Ann Radiol
1982; 23: 207-9.
10. Orecchia R, Rampino M, Gribaudo S, et al. Interstitial brachytherapy for carcinomas of the lower
lip. Results of treatment. Tumori 1991; 77: 336-8.
11. Pigneux J, Richaud PM, Lagarde C. The place of interstitial therapy using iridium 192 in the
management of carcinoma of the lip. Cancer 1979; 43: 1073-77.
12. Tombolini V, Bonanni A, Valeriani M, et al. Brachytherapy for squamous cell carcinoma of the lip.
The experience of the Institute of Radiology of the University of Rome “La Sapienza”. Tumori
1998; 84(4): 478-82.
13. Van Limbergen E, Ding W, Haustermans K, et al. Lip cancer: local control results of low dose
rate brachytherapy. The GEC-ESTRO 1993 survey on 2800 cases. ( unpublished data presented
at the annual GEC ESTRO meeting Venice 1993)