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A retrospective study of three treatment techniques for T1-T2 base of tongue lesions: Surgery plus postoperative radiation, external radiation plus interstitial implantation and external radiation alone
Inr. J. Radiation Oncology Biol. Phys., Vol. 13, pp. 51 l-516 Printed in the U.S.A. All rights reserved.
0360-3016/87 $3.00 + .CKl Copyright 0 1987 Pergamon Journals Ltd.
??Original Contribution A RETROSPECTIVE STUDY OF THREE TREATMENT TECHNIQUES FOR Tl-T2 BASE OF TONGUE LESIONS: SURGERY PLUS POSTOPERATIVE RADIATION, EXTERNAL RADIATION PLUS INTERSTITIAL IMPLANTATION AND EXTERNAL RADIATION ALONE MARTIN HOUSSET, M.D., FRANC• ISBAILLET, M.D., BERNADETTE DESSARD-DIANA, DANIEL MARTIN, M.D. AND LAURENT MIGLIANICO, M.D.
M.D.,
Centrede Traitementdes Tumeurs,Hopital Necker,Universitt de ParisV, France One hundredand ten patientswith base of tongue tumorsless than or equal to 4 cm in diameter(Ti and T2 by the UICC staging system) weretreatedaccordingto three diierent methods;surgeryfollowedby externalradiationin 27 cases, external radiationfollowed by interstitial implantationin 29 csses, and external radiationalone in 54 cases. The median follow-up is 8 years with a minimum of 4 years. Local failure occurred twice as often in patients treated by external radiation alone (43%) compared to the other two therapeutic modalities (20.5% for external radiation plus implantation and 18.5% for surgery plus radiation). Ninety per cent of recurrences occurred within the first 2 years. The 5-year survival rate for NO and Nl nodal disease is 20.5% for patients treated by external radiation alone and 50% for the other two methods. This survival difference is related to poorer local control. Surgery plus external radiation gives identical results to those of external radiation and interstitial implantation, but surgery is only practical for peripheral base of tongue tumors and it has poorer functional results. External radiation followed by interstitial implantation is, in our opinion, the best of the three therapeutic techniques for Tl and T2 base of tongue tumors. Base of tongue cancer, Radiation therapy, Surgery, Interstitial implants, Iridium”* afterloading.
INTRODUCTION
1’Hopital Necker between January 1974 and December 198 1. It compares three therapeutic methods: surgery plus postoperative radiation, external radiation alone, and external radiation followed by interstitial implantation,
Methods of treatment for T 1 and T2 base of tongue carcinomas (measuring less than or equal to 4 cm) usually include surgery combined with external radiation or external radiation alone. Surgical treatment of base of tongue tumors requires extensive resection of the oropharyngeal tongue, which results in significant functional deficits. It is therefore reserved for peripherally located base of tongue lesions. Fortunately, total laryngectomy is not generally required for Tl-T2 tumors. External radiation alone is the most common treatment modality and is applicable for all primary tumor sites of base of tongue tumors (central and peripheral). The remaining treatment modality, which is less commonly used for T 1-T2 base of tongue tumors, is the combination of external radiation and interstitial implantation. This paper presents results of these three treatments techniques with the intent of improving patient selection for the most appropriate modality in the future. This paper is a retrospective study of 110 patients who were irradiated at the Centre de Traitement des Tumeurs de
METHODS
AND
MATERIALS
Between January 1974 and December 198 1, 110 patients were treated for epidermoid carcinoma of the base of tongue. These were Tl and T2 tumors by the 1978 UICC staging system. The median follow-up time was 8 years, with a maximum of 12 years, and a minimum of 4 years. There were 98 males (89%) and 12 females ( 11%). The median age was 56 years, with the range being 30 to 82. None of the patients had been previously treated for another cancer. Surgery with postoperative radiation was used in 27 patients, primarily presenting peripherally located base of tongue lesions. External radiation followed by interstitial implantation was used in 29 patients, primarily pre-
Reprint requests to: Professor Franqois BaiIIet, Centre de Traitement des Tumeurs, Hopital Necker, 149 rue de S&es, 75015, Paris, France.
Accepted for publication 4 November 1986.
511
512
I. J. RadiationOncology0 Biology0 Physics
April 1987,Volume13,Number4
Table 1. Patient distribution: 110 cases, T l-T2 base of tongue tumors External radiation plus implantation (29 patients)
Surgery plus external radiation (27 patients)
External radiation alone (54 patients)
57.3 yrs (32-76) 2.9 cm
52.4 yrs (30-69) 2.8 cm
57.5 yrs (32-82) 2.6 cm
Median age Mean tumor diameter Tumor stage Tl T2 Nodal stage* NO NI N3 Percentage with purely exophytic morphology
20.7% 6129 79.3% 23129
26% 74%
7127 20127
35.2% I9154 64.8% 35154
58.6% 17129 20.7% 6129 20.7% 6129
44.5% 12127 37% IO/27 18.5% 5127
42.6% 23154 20.4% 1l/54 37% 20154
21%
22%
44%
6129
6127
24154
* There were no patients with N2 disease.
senting centrally located lesions. External radiation alone was used in 54 patients for all lesions locations but primarily of exophytic morphology and/or of N3 stage. Table 1 shows the distribution of patients by treatment technique. The T and N stages of the tumor, the mean tumor diameter, the median age, and the macroscopic description are presented. The table shows the patient characteristics of the three treatment groups to be comparable. Surgery Methods of surgery carried out in 27 cases included 2 1 patients treated by subglossectomy with horizontal supraglottic laryngectomy. This was done for carcinomas extending to the vallecula but not extending beyond the posterior half of the base of tongue. Four patients were treated by subglossectomy with trans-maxillary buccopharyngectomy for lateralized carcinomas which extended to the glossotonsillar sulcus or beyond. Two patients were treated by deep diathermy for centrally situated tumors. No total laryngectomy was performed. Neck node dissection was carried out on all patients treated by combined surgery plus external radiation. Most patients had bilateral neck node dissection, either radical or conservative, depending on whether palpable adenopathy was present. Irradiation External radiation therapy was given by a @‘Comachine.* Two opposed lateral parallel beams were used to encompass the site of the primary tumor and the upper and middle cervical lymph nodes. The lower cervical lymph nodes were treated by a single anterior split beam. Radiation was given daily, five times weekly, delivering
* Picker 9 CM go-Picker Corporation, USA; Alcyon-Thomson CGR, France.
1.8 Gy at the 95% isodose line. All fields were treated daily. For those patients treated by combined surgery plus postoperative radiation, the radiation was begun within 4 weeks after surgery and given to a total dose of 45 grays. When there was extracapsular spread of tumor, or when there were close pathologic margins, 55 Gy was given to the cervical lymph nodes of the involved side. For those patients treated by external radiation alone, the dose to the tumor and adjacent palpable lymph nodes ranged between 70 and 75 Gy, with a mean dose of 72 grays. Forty-five grays were given prophylactically to clinically negative nodal areas. For those patients treated by external radiation followed by implantation, the external dose was 45 Gy at the base of tongue and lymph node areas. Implantation of the primary tumor was carried out within 3 weeks following completion of external radiation. The procedure was done under general anesthesia using flexible plastic tubes. We used the plastic-loop technique: HolIow needles were inserted into the base of tongue through the submental area, the position being monitored by palpation. A nylon thread was then pushed through the lumen of the needle and then the needle was removed. The plastic tube was pulled over the nylon thread. The two were coupled by clamping, and the plastic tube was pulled into position. Each plastic tube formed a loop with free ends in the submentum. These were placed parallel, an average of 15 mm apart, and encompassed the initial tumor volume. The depth of the tumor was presumed to be at least equal to the mean diameter of the tumor. The number of loops depended on the initial dimension of the tumor. Post-operatively orthogonal localization radiographs were taken with dummy sources in the catheters (Figs. 1A and 1B) and a computerized dose distribution
Tl-T2 base of tongue tumors 0 M. HOUSSETet al.
513
Fig. 1. (A and 1B) Orthogonal localization radiographs of the implantation, with dummy sources in the plastic tubes for verification of sources position and dose calculations.
was performed. Iridium’92 wires were afterloaded into plastic tubes and the radiation dose delivered was 30 to 35 Gy specified at a reference isodose. This reference isodose (Fig. 2) was determined in a plane crossing the center of the ends of the loops and corresponded to 85% of
the basal isodose (i.e. the first continuous isodose inside the application). When adenopathy persisted after 45 Gy external radiation, neck dissection was carried out. When adenopathy was present at the original diagnosis, but had disappeared at the end of 45 Gy, an electron boost was given to the originally involved areas to a total dose of 70 to 75 grays. RESULTS
( WDq)
tsscus3
_ -
28.49
__
16.76
-
1425
__-____
/’ ) / IO/ ,’
I
/
.*
‘._.-
/
Fig. 2. Computerized dose distribution in a plane crossing the center of the ends of the loops. The reference isodose corresponded to 85% of the first continuous isodose inside the application.
Local and regional control Table 2 gives the proportion of local failures of primary tumors in relation to the treatment technique applied. In the groups of patients treated by external radiation alone the local failure rate was twice as high at 43% (23/54) as that of the other two methods (p < 0.05); it was 20.5% (6/29) for external beam therapy plus implantation and 18.5% (5/27) for surgery plus external radiation. The details of tumor failures are summarized in Table 3. For those patients treated by external radiation alone, T2 or infiltrative tumors had more frequent local failures than Tl or exophytic, non-infiltrative tumors. Local control was better for patients treated by external radiation and implantation; local failures were seen only
514
I. J. Radiation Oncology 0 Biology 0 Physics
April 1987, Volume 13, Number 4
Table 2. Local control of primary tumors by treatment technique External radiation plus implantation Primary local failures’ Secondary local failures2 Total local failures
Surgery plus external radiation
Table 4. Analysis of lymph node failures
External radiation alone
14% 4129
4% l/27*
8% 2125
15% 4126
35% 17148
20% 6129
19% 5127
43% 23154
’Residual disease at completion of treatment. 2 Recurrence of primary tumor greater than completion of treatment (ah these patients had plete response). * One patient had a cut-through at the time the post-operative dose was therefore increased
11%
6/54
6 months after an initial comof surgery, and to 70 Gy.
in T2 tumors. For this technique, in contrast to external
radiation alone, the patients with both infiltrative and exophytic tumors had equal failure rates. For patients treated by surgery followed by external radiation, results were comparable to those of external radiation plus implantation. In this group frequency of tumor failures was independent of tumor size and macroscopic description. The average period before local recurrence was 15 months, which was identical in all three groups. Ninety percent (30/34) of tumor recurrences occurred within the first 2 years. Only 3 primary tumor failures were salvaged from the external radiation alone treatment group, all by curietherapy. No tumoral failures from the other two treatment groups could be salvaged by any altemative therapeutic methods. The results of nodal failures are summarized in Table 4. No contralateral nodal failure have been observed. For the NO and N 1 groups, there was a 4% (3/79) risk of failure. In the N3 group there was a 28% (lo/3 1) risk of failure. In this N3 group, there were twice as many failures 40% (8/20) in the external radiation alone group compared to the other two groups. This consisted of a 20% (l/5) failure rate for the surgery plus external radiation group, and 16.5% (l/6) failure rate for the external radiation plus implantation group (it must be noted that 3/6
NO Nl N3
External radiation plus implantation
Surgery plus external radiation
External radiation alone
l/17 O/6 116 16.5%
o/12 o/10 115 20%
l/23 l/11 8120 40%
of the N3 patients of this last group were subjected to neck node dissection after 45 Gy external radiation). Survival Actuarial survival at 5 years (Fig. 3) is 52% for the external radiation plus implantation group, 49% for the surgery plus radiation group, and 17% for the external radiation alone group (p < 0.02). A study of the causes of death (Table 5) shows that, in this latter group, the death-rate from metastatic nodal disease and progressive primary tumors is far greater than that of the two other groups. As the external radiation alone group had twice as many N3 patients, we excluded all N3 patients in the comparison of 5-year survival rates for all three groups. With this exclusion of all N3 patients, there was a 20% difference in the 5-year survival of the NO and Nl patients (Fig. 4), but not statistically significant (p = 0.20): The 5-year survival rates was 30.5% for external radiation alone versus 50% and 5 1% for the other two modalities. This difference could be explained by the poorer local control for the external radiation group. Complications In the group treated by external radiation plus implantation, necrosis occurred in only three patients; two with soft tissue necrosis which healed with medical management, and one with osteoradionecrosis arising from an application where a radioactive wire had been in contact with the mandible. Furthermore, external radiation plus interstitial implantation has permitted delivery of smaller doses to the salivary glands, the masseter muscles, and the temporomandibular joint. There has been no trismus and no severe xerostomia.
Table 3. Analysis of tumor failures by treatment technique External radiation plus implantation Total tumor failures Tl failures T2 failures Exophytic morphology Infdtrative and ulceroinfiltrative morphology
Surgery plus external radiation
External radiation alone
20% 0% 26%
6129 O/6 6123
19% 28% 15%
5127 217 3120
43% 21% 53%
23154 4119 19135
16%
f/6
16%
l/6
33%
8124
22%
5123
19%
412 1
50%
15130
T l-T2 base of
100
-_
rdiationplus implmntetion (29 ptlants)
90 80
*- edernel
+ oxtarn rdlationplua impltntation(23pMie~8)
- sur9wyplaext8rml rdltion (27 paMW
+- turgwyplwaxternal rdiation~22patlentd
* axtarn rdiatione~on(54
70
* externlrailationJon8(34
wtientd
FL 60 1. x
515
tongue tumors 0 M. HOUSSETet al.
‘~--=+__52%
so-.
49%
40 .. 30 .. 20 ..
\
IO
‘1: 0
17% t OJ
I
2
3
4
,
0
5
1
2
3
4
5
YEARS
Fig. 4. Survival by treatment technique, NO-N 1.
Fig. 3. Survival by treatment technique, any N.
In the group treated by surgery and external radiation, complications related to external radiation were identical to the group above. Osteonecrosis was noted in 1 patient and a postsurgical residual oedema in 2 patients. However, surgery triggered classical troubles in elocution and/or swallowing. In the group treated by external radiation alone, a marked fibrosis leading to a significant mobility impairment was observed in 1 patient. Xerostomia was generalized and significant. DISCUSSION The poor results obtained from surgery alone in the treatment of base of tongue tumors, T 1-T2 included, has led to the combination of surgery with radiation.3 Unfortunately, surgery is only useful for peripheral base of tongue tumors. For the remaining base of tongue tumors, external radiation therapy is the most commonly used treatment. The local control rate using radiotherapy depends on the size of the tumor and also on the dose delivered. Spanos et al.* had a local control rate of 9 1% for T 1, and 7 1% for T2 tumors. Parsons et aL5 revealed a local control rate of 75% for Tl and 67% for T2 tumors. In the latter study,
some patients received a radium boost, the benefits of which were evident only for T 1 tumors. Interstitial implants have not been used frequently for base of tongue tumors. This has been caused by several problems including the use of rigid radium needles and the difficulties associated with their placement. This situation has been improved by the use of flexible plastic tubes which allow afterloading of radioactive material, the discovery of newer and safer isotopes (such as Iridium19*), and the computerized calculation ofisodose distributions. With these improvements, the flexibility of the system has allowed treatment of base of tongue tumors even involving the vallecula or the glossotonsillar sulcus. Several authors1,2,6 have pointed out the advantages of interstitial implantation of the base of tongue. There are a variety of techniques available to treat this site,2g4,6*7,9*‘o making easier precise application possible. Results from these techniques have a local failure rate between 14 and 3 1%. However, these studies include T 1 to T4 tumors, and also include previously treated patients. The present study covers 110 Tl and T2 base of tongue tumors which were radiated by the same personnel. The median follow-up period was 8 years with a minimum of 4 years. It compares the results of three
Table 5. Analysis of the causes of death External radiation plus implantation Tumor failures Isolated lymph node failures Metastatic disease New Primary cancer Other causes Undetermined
Surgery plus external radiation
6
20.5%
5
2
1 7% 5
1
14129
18.5%
External radiation alone 20
37%
4% 2 1 4 13127
10
3 18.5% 2 6 4
45154
516
I. J. Radiation Oncology 0 Biology 0 Physics
different therapeutic methods. The local failure rate is twice as high for external radiation therapy alone compared to the other two methods and has a proportionately lower 5-year survival rate. For NO and Nl disease the 5-year survival rate ranges from 30.5% for external radiation alone to more than 50% for the other two methods. For all cases, including the N3 group, the 5year survival rate increases from 17 to 50%. External radiation plus interstitial implantation gives better local control in T 1 and T2 base of tongue tumors as compared to external radiation alone. For patients treated by external radiation alone, good prognostic indicators include tumors less than 2 cm in diameter and purely exophytic morphology. However, even in this group, results are better with external radiation plus implantation. These advantages are not associated with an increase in complication rates. Surgery with postoperative radiation in Tl and T2 base of tongue tumors provides equal control and survival rates to external radiation plus implantation. How-
April 1987, Volume 13, Number 4
ever, surgery is technically practical only for peripheral
tumors, in contrast to implantation which is practical for all Tl and T2 tumors. With radiation treatment alone, significant chronic sequalae are minimal. Even if lymphadenopathy is present, there is no contraindication to implantation. The enlarged nodes can be treated by primary external radiation with additional neck dissection or electron boost if necessary. Our results show that external radiation with interstitial implantation for Tl and T2 base of tongue tumors is better than external radiation alone. This includes a comparison of local efficacy, survival, and the quality of functional results. Surgery with postoperative radiation gives equal results for local control and survival but is applicable only to peripheral base of tongue tumors. Furthermore, the functional results are not as good as those of external radiation plus interstitial implantation, which, in our opinion, is the best of the three treatment modalities for T 1 and T2 base of tongue tumors.
REFERENCES 1. Baillet, F., Deluen, F., Delpon, A., Housset, M., Maylin,
C., Perret, M.: L.aradiotherapie des epitheliomas de la base de la langue. Actualit& de Carcinologie Cervico-Faciale 9:
168-175,1983. 2. Goffinet, D.R., Fee, W.E., Wells, J., Austin-Seymour, M., Clarke, D., Marischal, J.M., Goode, R.L.: 192 Ir Pharyngoepiglottic Fold Interstitial Implants: The key to successful treatment of base of tongue carcinoma by radiation therapy. Cancer 55: 941-948,1985. 3. Jesse, R.H., Lindberg, R.D.: The efficacy of combining radiation therapy with a surgical procedure in patients with cervical metastasis from squamous cancer of the oropharynxand hypopharynx. Cancer35 1163-l 166, 1975.
4. Mira, J.G., Gates, G.A., Whiteley, A.B.: Technique modification for radioactive implants when plastic tubes are used in fibrosed head and neck areas. Int. J. Radiat. Oncol. Biol. Phys. 8: 1799-1801, 1982. 5. Parsons, J.T., Million, R.R., Cassisi, N.J.: Carcinoma of the base of the tongue: Results of radical irradiation with
6.
7.
8.
9.
10.
surgery reserved for irradiation failure. Laryngoscope 92: 689-696,1982. Pierquin, B.: Brachytherapy, Pierquin, B., Chassagne, D.J., Chahbazian, C.M., Wilson, J.F. (Eds.). St. Louis, Missouri, Warren H. Green Inc. 1978, p. 119. Puthawala, A.A., Nisar Syed, A.M., Neblett, D., McNamara, C.: The role of afterloading iridium implants in the management of the carcinoma of the tongue. Int. J. Radiat. Oncol. Biol. Phys. 7: 407-4 12, 198 1. Spanos, W.J., Shukovsky, L.J., Flecher, G.H.: Time, dose and tumor volume relationships in irradiation of squamous cell of the base of the tongue. Cancer 40: 259 l-2599, 1976. Vikram, B., Hilaris, B.S.: A non looping afterloading technique for interstitial implants of the base of tongue. Int. J. Radiol. Oncol. Biol. Phys. 7: 4 10-422, 198 1. Vikram, B., Strong, E., Shah, J., Spiro, R., Gerold, F., Sessions, R., Hilaris, B.: A non-looping technique for base of tongue implants: Results in the first 20 patients. Int. J. Radiat. Oncol. Biol. Phys. 11: 1853-1855, 1985.
0360-3016/87 $3.00 + .CKl Copyright 0 1987 Pergamon Journals Ltd.
??Original Contribution A RETROSPECTIVE STUDY OF THREE TREATMENT TECHNIQUES FOR Tl-T2 BASE OF TONGUE LESIONS: SURGERY PLUS POSTOPERATIVE RADIATION, EXTERNAL RADIATION PLUS INTERSTITIAL IMPLANTATION AND EXTERNAL RADIATION ALONE MARTIN HOUSSET, M.D., FRANC• ISBAILLET, M.D., BERNADETTE DESSARD-DIANA, DANIEL MARTIN, M.D. AND LAURENT MIGLIANICO, M.D.
M.D.,
Centrede Traitementdes Tumeurs,Hopital Necker,Universitt de ParisV, France One hundredand ten patientswith base of tongue tumorsless than or equal to 4 cm in diameter(Ti and T2 by the UICC staging system) weretreatedaccordingto three diierent methods;surgeryfollowedby externalradiationin 27 cases, external radiationfollowed by interstitial implantationin 29 csses, and external radiationalone in 54 cases. The median follow-up is 8 years with a minimum of 4 years. Local failure occurred twice as often in patients treated by external radiation alone (43%) compared to the other two therapeutic modalities (20.5% for external radiation plus implantation and 18.5% for surgery plus radiation). Ninety per cent of recurrences occurred within the first 2 years. The 5-year survival rate for NO and Nl nodal disease is 20.5% for patients treated by external radiation alone and 50% for the other two methods. This survival difference is related to poorer local control. Surgery plus external radiation gives identical results to those of external radiation and interstitial implantation, but surgery is only practical for peripheral base of tongue tumors and it has poorer functional results. External radiation followed by interstitial implantation is, in our opinion, the best of the three therapeutic techniques for Tl and T2 base of tongue tumors. Base of tongue cancer, Radiation therapy, Surgery, Interstitial implants, Iridium”* afterloading.
INTRODUCTION
1’Hopital Necker between January 1974 and December 198 1. It compares three therapeutic methods: surgery plus postoperative radiation, external radiation alone, and external radiation followed by interstitial implantation,
Methods of treatment for T 1 and T2 base of tongue carcinomas (measuring less than or equal to 4 cm) usually include surgery combined with external radiation or external radiation alone. Surgical treatment of base of tongue tumors requires extensive resection of the oropharyngeal tongue, which results in significant functional deficits. It is therefore reserved for peripherally located base of tongue lesions. Fortunately, total laryngectomy is not generally required for Tl-T2 tumors. External radiation alone is the most common treatment modality and is applicable for all primary tumor sites of base of tongue tumors (central and peripheral). The remaining treatment modality, which is less commonly used for T 1-T2 base of tongue tumors, is the combination of external radiation and interstitial implantation. This paper presents results of these three treatments techniques with the intent of improving patient selection for the most appropriate modality in the future. This paper is a retrospective study of 110 patients who were irradiated at the Centre de Traitement des Tumeurs de
METHODS
AND
MATERIALS
Between January 1974 and December 198 1, 110 patients were treated for epidermoid carcinoma of the base of tongue. These were Tl and T2 tumors by the 1978 UICC staging system. The median follow-up time was 8 years, with a maximum of 12 years, and a minimum of 4 years. There were 98 males (89%) and 12 females ( 11%). The median age was 56 years, with the range being 30 to 82. None of the patients had been previously treated for another cancer. Surgery with postoperative radiation was used in 27 patients, primarily presenting peripherally located base of tongue lesions. External radiation followed by interstitial implantation was used in 29 patients, primarily pre-
Reprint requests to: Professor Franqois BaiIIet, Centre de Traitement des Tumeurs, Hopital Necker, 149 rue de S&es, 75015, Paris, France.
Accepted for publication 4 November 1986.
511
512
I. J. RadiationOncology0 Biology0 Physics
April 1987,Volume13,Number4
Table 1. Patient distribution: 110 cases, T l-T2 base of tongue tumors External radiation plus implantation (29 patients)
Surgery plus external radiation (27 patients)
External radiation alone (54 patients)
57.3 yrs (32-76) 2.9 cm
52.4 yrs (30-69) 2.8 cm
57.5 yrs (32-82) 2.6 cm
Median age Mean tumor diameter Tumor stage Tl T2 Nodal stage* NO NI N3 Percentage with purely exophytic morphology
20.7% 6129 79.3% 23129
26% 74%
7127 20127
35.2% I9154 64.8% 35154
58.6% 17129 20.7% 6129 20.7% 6129
44.5% 12127 37% IO/27 18.5% 5127
42.6% 23154 20.4% 1l/54 37% 20154
21%
22%
44%
6129
6127
24154
* There were no patients with N2 disease.
senting centrally located lesions. External radiation alone was used in 54 patients for all lesions locations but primarily of exophytic morphology and/or of N3 stage. Table 1 shows the distribution of patients by treatment technique. The T and N stages of the tumor, the mean tumor diameter, the median age, and the macroscopic description are presented. The table shows the patient characteristics of the three treatment groups to be comparable. Surgery Methods of surgery carried out in 27 cases included 2 1 patients treated by subglossectomy with horizontal supraglottic laryngectomy. This was done for carcinomas extending to the vallecula but not extending beyond the posterior half of the base of tongue. Four patients were treated by subglossectomy with trans-maxillary buccopharyngectomy for lateralized carcinomas which extended to the glossotonsillar sulcus or beyond. Two patients were treated by deep diathermy for centrally situated tumors. No total laryngectomy was performed. Neck node dissection was carried out on all patients treated by combined surgery plus external radiation. Most patients had bilateral neck node dissection, either radical or conservative, depending on whether palpable adenopathy was present. Irradiation External radiation therapy was given by a @‘Comachine.* Two opposed lateral parallel beams were used to encompass the site of the primary tumor and the upper and middle cervical lymph nodes. The lower cervical lymph nodes were treated by a single anterior split beam. Radiation was given daily, five times weekly, delivering
* Picker 9 CM go-Picker Corporation, USA; Alcyon-Thomson CGR, France.
1.8 Gy at the 95% isodose line. All fields were treated daily. For those patients treated by combined surgery plus postoperative radiation, the radiation was begun within 4 weeks after surgery and given to a total dose of 45 grays. When there was extracapsular spread of tumor, or when there were close pathologic margins, 55 Gy was given to the cervical lymph nodes of the involved side. For those patients treated by external radiation alone, the dose to the tumor and adjacent palpable lymph nodes ranged between 70 and 75 Gy, with a mean dose of 72 grays. Forty-five grays were given prophylactically to clinically negative nodal areas. For those patients treated by external radiation followed by implantation, the external dose was 45 Gy at the base of tongue and lymph node areas. Implantation of the primary tumor was carried out within 3 weeks following completion of external radiation. The procedure was done under general anesthesia using flexible plastic tubes. We used the plastic-loop technique: HolIow needles were inserted into the base of tongue through the submental area, the position being monitored by palpation. A nylon thread was then pushed through the lumen of the needle and then the needle was removed. The plastic tube was pulled over the nylon thread. The two were coupled by clamping, and the plastic tube was pulled into position. Each plastic tube formed a loop with free ends in the submentum. These were placed parallel, an average of 15 mm apart, and encompassed the initial tumor volume. The depth of the tumor was presumed to be at least equal to the mean diameter of the tumor. The number of loops depended on the initial dimension of the tumor. Post-operatively orthogonal localization radiographs were taken with dummy sources in the catheters (Figs. 1A and 1B) and a computerized dose distribution
Tl-T2 base of tongue tumors 0 M. HOUSSETet al.
513
Fig. 1. (A and 1B) Orthogonal localization radiographs of the implantation, with dummy sources in the plastic tubes for verification of sources position and dose calculations.
was performed. Iridium’92 wires were afterloaded into plastic tubes and the radiation dose delivered was 30 to 35 Gy specified at a reference isodose. This reference isodose (Fig. 2) was determined in a plane crossing the center of the ends of the loops and corresponded to 85% of
the basal isodose (i.e. the first continuous isodose inside the application). When adenopathy persisted after 45 Gy external radiation, neck dissection was carried out. When adenopathy was present at the original diagnosis, but had disappeared at the end of 45 Gy, an electron boost was given to the originally involved areas to a total dose of 70 to 75 grays. RESULTS
( WDq)
tsscus3
_ -
28.49
__
16.76
-
1425
__-____
/’ ) / IO/ ,’
I
/
.*
‘._.-
/
Fig. 2. Computerized dose distribution in a plane crossing the center of the ends of the loops. The reference isodose corresponded to 85% of the first continuous isodose inside the application.
Local and regional control Table 2 gives the proportion of local failures of primary tumors in relation to the treatment technique applied. In the groups of patients treated by external radiation alone the local failure rate was twice as high at 43% (23/54) as that of the other two methods (p < 0.05); it was 20.5% (6/29) for external beam therapy plus implantation and 18.5% (5/27) for surgery plus external radiation. The details of tumor failures are summarized in Table 3. For those patients treated by external radiation alone, T2 or infiltrative tumors had more frequent local failures than Tl or exophytic, non-infiltrative tumors. Local control was better for patients treated by external radiation and implantation; local failures were seen only
514
I. J. Radiation Oncology 0 Biology 0 Physics
April 1987, Volume 13, Number 4
Table 2. Local control of primary tumors by treatment technique External radiation plus implantation Primary local failures’ Secondary local failures2 Total local failures
Surgery plus external radiation
Table 4. Analysis of lymph node failures
External radiation alone
14% 4129
4% l/27*
8% 2125
15% 4126
35% 17148
20% 6129
19% 5127
43% 23154
’Residual disease at completion of treatment. 2 Recurrence of primary tumor greater than completion of treatment (ah these patients had plete response). * One patient had a cut-through at the time the post-operative dose was therefore increased
11%
6/54
6 months after an initial comof surgery, and to 70 Gy.
in T2 tumors. For this technique, in contrast to external
radiation alone, the patients with both infiltrative and exophytic tumors had equal failure rates. For patients treated by surgery followed by external radiation, results were comparable to those of external radiation plus implantation. In this group frequency of tumor failures was independent of tumor size and macroscopic description. The average period before local recurrence was 15 months, which was identical in all three groups. Ninety percent (30/34) of tumor recurrences occurred within the first 2 years. Only 3 primary tumor failures were salvaged from the external radiation alone treatment group, all by curietherapy. No tumoral failures from the other two treatment groups could be salvaged by any altemative therapeutic methods. The results of nodal failures are summarized in Table 4. No contralateral nodal failure have been observed. For the NO and N 1 groups, there was a 4% (3/79) risk of failure. In the N3 group there was a 28% (lo/3 1) risk of failure. In this N3 group, there were twice as many failures 40% (8/20) in the external radiation alone group compared to the other two groups. This consisted of a 20% (l/5) failure rate for the surgery plus external radiation group, and 16.5% (l/6) failure rate for the external radiation plus implantation group (it must be noted that 3/6
NO Nl N3
External radiation plus implantation
Surgery plus external radiation
External radiation alone
l/17 O/6 116 16.5%
o/12 o/10 115 20%
l/23 l/11 8120 40%
of the N3 patients of this last group were subjected to neck node dissection after 45 Gy external radiation). Survival Actuarial survival at 5 years (Fig. 3) is 52% for the external radiation plus implantation group, 49% for the surgery plus radiation group, and 17% for the external radiation alone group (p < 0.02). A study of the causes of death (Table 5) shows that, in this latter group, the death-rate from metastatic nodal disease and progressive primary tumors is far greater than that of the two other groups. As the external radiation alone group had twice as many N3 patients, we excluded all N3 patients in the comparison of 5-year survival rates for all three groups. With this exclusion of all N3 patients, there was a 20% difference in the 5-year survival of the NO and Nl patients (Fig. 4), but not statistically significant (p = 0.20): The 5-year survival rates was 30.5% for external radiation alone versus 50% and 5 1% for the other two modalities. This difference could be explained by the poorer local control for the external radiation group. Complications In the group treated by external radiation plus implantation, necrosis occurred in only three patients; two with soft tissue necrosis which healed with medical management, and one with osteoradionecrosis arising from an application where a radioactive wire had been in contact with the mandible. Furthermore, external radiation plus interstitial implantation has permitted delivery of smaller doses to the salivary glands, the masseter muscles, and the temporomandibular joint. There has been no trismus and no severe xerostomia.
Table 3. Analysis of tumor failures by treatment technique External radiation plus implantation Total tumor failures Tl failures T2 failures Exophytic morphology Infdtrative and ulceroinfiltrative morphology
Surgery plus external radiation
External radiation alone
20% 0% 26%
6129 O/6 6123
19% 28% 15%
5127 217 3120
43% 21% 53%
23154 4119 19135
16%
f/6
16%
l/6
33%
8124
22%
5123
19%
412 1
50%
15130
T l-T2 base of
100
-_
rdiationplus implmntetion (29 ptlants)
90 80
*- edernel
+ oxtarn rdlationplua impltntation(23pMie~8)
- sur9wyplaext8rml rdltion (27 paMW
+- turgwyplwaxternal rdiation~22patlentd
* axtarn rdiatione~on(54
70
* externlrailationJon8(34
wtientd
FL 60 1. x
515
tongue tumors 0 M. HOUSSETet al.
‘~--=+__52%
so-.
49%
40 .. 30 .. 20 ..
\
IO
‘1: 0
17% t OJ
I
2
3
4
,
0
5
1
2
3
4
5
YEARS
Fig. 4. Survival by treatment technique, NO-N 1.
Fig. 3. Survival by treatment technique, any N.
In the group treated by surgery and external radiation, complications related to external radiation were identical to the group above. Osteonecrosis was noted in 1 patient and a postsurgical residual oedema in 2 patients. However, surgery triggered classical troubles in elocution and/or swallowing. In the group treated by external radiation alone, a marked fibrosis leading to a significant mobility impairment was observed in 1 patient. Xerostomia was generalized and significant. DISCUSSION The poor results obtained from surgery alone in the treatment of base of tongue tumors, T 1-T2 included, has led to the combination of surgery with radiation.3 Unfortunately, surgery is only useful for peripheral base of tongue tumors. For the remaining base of tongue tumors, external radiation therapy is the most commonly used treatment. The local control rate using radiotherapy depends on the size of the tumor and also on the dose delivered. Spanos et al.* had a local control rate of 9 1% for T 1, and 7 1% for T2 tumors. Parsons et aL5 revealed a local control rate of 75% for Tl and 67% for T2 tumors. In the latter study,
some patients received a radium boost, the benefits of which were evident only for T 1 tumors. Interstitial implants have not been used frequently for base of tongue tumors. This has been caused by several problems including the use of rigid radium needles and the difficulties associated with their placement. This situation has been improved by the use of flexible plastic tubes which allow afterloading of radioactive material, the discovery of newer and safer isotopes (such as Iridium19*), and the computerized calculation ofisodose distributions. With these improvements, the flexibility of the system has allowed treatment of base of tongue tumors even involving the vallecula or the glossotonsillar sulcus. Several authors1,2,6 have pointed out the advantages of interstitial implantation of the base of tongue. There are a variety of techniques available to treat this site,2g4,6*7,9*‘o making easier precise application possible. Results from these techniques have a local failure rate between 14 and 3 1%. However, these studies include T 1 to T4 tumors, and also include previously treated patients. The present study covers 110 Tl and T2 base of tongue tumors which were radiated by the same personnel. The median follow-up period was 8 years with a minimum of 4 years. It compares the results of three
Table 5. Analysis of the causes of death External radiation plus implantation Tumor failures Isolated lymph node failures Metastatic disease New Primary cancer Other causes Undetermined
Surgery plus external radiation
6
20.5%
5
2
1 7% 5
1
14129
18.5%
External radiation alone 20
37%
4% 2 1 4 13127
10
3 18.5% 2 6 4
45154
516
I. J. Radiation Oncology 0 Biology 0 Physics
different therapeutic methods. The local failure rate is twice as high for external radiation therapy alone compared to the other two methods and has a proportionately lower 5-year survival rate. For NO and Nl disease the 5-year survival rate ranges from 30.5% for external radiation alone to more than 50% for the other two methods. For all cases, including the N3 group, the 5year survival rate increases from 17 to 50%. External radiation plus interstitial implantation gives better local control in T 1 and T2 base of tongue tumors as compared to external radiation alone. For patients treated by external radiation alone, good prognostic indicators include tumors less than 2 cm in diameter and purely exophytic morphology. However, even in this group, results are better with external radiation plus implantation. These advantages are not associated with an increase in complication rates. Surgery with postoperative radiation in Tl and T2 base of tongue tumors provides equal control and survival rates to external radiation plus implantation. How-
April 1987, Volume 13, Number 4
ever, surgery is technically practical only for peripheral
tumors, in contrast to implantation which is practical for all Tl and T2 tumors. With radiation treatment alone, significant chronic sequalae are minimal. Even if lymphadenopathy is present, there is no contraindication to implantation. The enlarged nodes can be treated by primary external radiation with additional neck dissection or electron boost if necessary. Our results show that external radiation with interstitial implantation for Tl and T2 base of tongue tumors is better than external radiation alone. This includes a comparison of local efficacy, survival, and the quality of functional results. Surgery with postoperative radiation gives equal results for local control and survival but is applicable only to peripheral base of tongue tumors. Furthermore, the functional results are not as good as those of external radiation plus interstitial implantation, which, in our opinion, is the best of the three treatment modalities for T 1 and T2 base of tongue tumors.
REFERENCES 1. Baillet, F., Deluen, F., Delpon, A., Housset, M., Maylin,
C., Perret, M.: L.aradiotherapie des epitheliomas de la base de la langue. Actualit& de Carcinologie Cervico-Faciale 9:
168-175,1983. 2. Goffinet, D.R., Fee, W.E., Wells, J., Austin-Seymour, M., Clarke, D., Marischal, J.M., Goode, R.L.: 192 Ir Pharyngoepiglottic Fold Interstitial Implants: The key to successful treatment of base of tongue carcinoma by radiation therapy. Cancer 55: 941-948,1985. 3. Jesse, R.H., Lindberg, R.D.: The efficacy of combining radiation therapy with a surgical procedure in patients with cervical metastasis from squamous cancer of the oropharynxand hypopharynx. Cancer35 1163-l 166, 1975.
4. Mira, J.G., Gates, G.A., Whiteley, A.B.: Technique modification for radioactive implants when plastic tubes are used in fibrosed head and neck areas. Int. J. Radiat. Oncol. Biol. Phys. 8: 1799-1801, 1982. 5. Parsons, J.T., Million, R.R., Cassisi, N.J.: Carcinoma of the base of the tongue: Results of radical irradiation with
6.
7.
8.
9.
10.
surgery reserved for irradiation failure. Laryngoscope 92: 689-696,1982. Pierquin, B.: Brachytherapy, Pierquin, B., Chassagne, D.J., Chahbazian, C.M., Wilson, J.F. (Eds.). St. Louis, Missouri, Warren H. Green Inc. 1978, p. 119. Puthawala, A.A., Nisar Syed, A.M., Neblett, D., McNamara, C.: The role of afterloading iridium implants in the management of the carcinoma of the tongue. Int. J. Radiat. Oncol. Biol. Phys. 7: 407-4 12, 198 1. Spanos, W.J., Shukovsky, L.J., Flecher, G.H.: Time, dose and tumor volume relationships in irradiation of squamous cell of the base of the tongue. Cancer 40: 259 l-2599, 1976. Vikram, B., Hilaris, B.S.: A non looping afterloading technique for interstitial implants of the base of tongue. Int. J. Radiol. Oncol. Biol. Phys. 7: 4 10-422, 198 1. Vikram, B., Strong, E., Shah, J., Spiro, R., Gerold, F., Sessions, R., Hilaris, B.: A non-looping technique for base of tongue implants: Results in the first 20 patients. Int. J. Radiat. Oncol. Biol. Phys. 11: 1853-1855, 1985.