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Treatment of oral cancer by interstitial irradiation using iridium—192
Journcrl
oi Oral
and
i lW2)
30. 355-359
I
r
Treatment of oral cancer by interstitial irradiation using iridium-192 J. M. Henk
SG’MM/I R Y. Sixty-seven patients with squamous cell carcinoma of the oral cavity were treated by implantation of radio-active iridium wire between 1977 and 1986. The results are presented in the hope of providing a comparison with those of primary surgical management. The crude 5-year survival rates were 61% for Tl, 74% for T2, and 37% for T3 tumours. The major causes of death were uncontrolled tumour in the neck and intercurrent disease. Seven of 52 patients with Tl or T2 tumours (13%) developed local recurrence at the primary site; five were salvaged surgically, for an ultimate failure rate of 4%. The ultimate failure for a group of 15 ‘~3 tumours was 47%. The only morbidity was a 31% incidence of soft tissue ulcers occurring during the first 18 months after treatment, none of which persisted. Elective external beam radiotherapy to the clinically negative neck significantly reduced the incidence of overt lymph node metastases.
INTRODL:CTlON
1977). Several studies have demonstrated superior results from interstitial compared with external irradiation (Wallner et al., 1986; Wendt et al., 1990). In the past 1.5 years. as better reconstructive techniques have been developed, surgery has become increasingly popular as the primary treatment for cancer so that the use of interstitial irradiation has declined. Some surgeons now maintain that most mouth cancers should be treated surgically, and that the only indication for radiotherapy is external beam post-operatively (McGregor. 1989). Thcrc is little dcbatc that surgery is the trcatmcnt of choice for very small lesions which can be easily excised with primary closure: or that advanced tumours infiltrating bone or deeply into muscle require surgery usually with post-opcrativc radiotherapy. However there is an intcrmcdiatc group consisting of the larger Tl and T2 and some earlier exophytic T3 tumours in which the relative merits of primary treatment by surgery or by radiotherapy remain debatable. As a consequence of the results of Pierquin et al (1970) which showed markedly bcttcr results from the use of iridium compared with radium, iridium wire implantation was introduced as a standard method of irradiation of oral cancer at the Royal Marsdcn Hospital in 1977. The results of the first 8 years experience are reviewed here, because although the technique is fairly widely used there is little information on the results obtained in the UK. It is hoped that the survival, local recurrcncc and morbidity rates reported here will provide a background for comparison with results of the newer surgical techniques.
Interstitial implantation of radio-active material has been a treatment option for oral cancer for 70 years. When the method was first introduced the only radioactive substances available were those occurring naturally i.e. radium and its daughter gaseous product radon. In the period before the Second World War the incidence of mouth cancer in the UK was considcrably higher than it is now. Radium nccdlcs wcrc used extensively cspccially for tongue cancer; surgeons were skilled in their use and results were generally good (Cade & Lee. 1957; De Croix & Ghosscin, 198 I). After the Second World War the hazards to staff from the use of radium became more apparent. At the same time supcrvoltagc external beam radiotherapy was being dcvcloped, so radium needling declined in popularity. However, the results of external beam irradiation proved disappointing (Morris. 1970) and the advent of new artificially-produced radio-active materials. cspccially caesium-I 37 and iridium-192. led to a renaissance of interstitial radiotherapy in the 1970’s (Paine. 1972). Interstitial irradiation is a suitable treatment for oral cancer provided the soft tissues are mobile and the tumour is at least 5 mm clear of adjacent bone. In such situations interstitial irradiation has considcrable biological advantages over external irradiation. The radiation from interstitial sources is delivered in a high dose to the vicinity of the tumour with minimal dosage to surrounding structures, therefore xcrostomia is not a sequel. Treatment is delivered over a few days, so that there is less tumour cell repopulation during treatment than in the case of external radiotherapy (Withers et al.. 1988) Also, the radiation is delivered continuously, at a low dose-rate, under which conditions hypoxic tumour cells may be less radio-resistant (Hall.
PATIENTS
AND METHODS
From 1977 through 1986. 67 patients with squamous carcinoma of the oral cavity were trcatcd by radical 355
356
British Journal
of Oral and Maxillofacial
Sureer\;
radiotherapy using iridium-192 implantation either alone or in combination with external radiotherapy. Forty-eight were male and 19 female. The median age was 63 years, the range 26-89 years. The choice of treatment policy between elective surgery or radical radiotherapy with surgery reserved for salvage was made at joint consultation bctwccn a surgcon and a radiotherapist. The reason for preferring radiotherapy in most of these patients was that it was considered likely to give a better functional result than surgery with an equal chance of survival. In 5 patients with advanced (T3) tumours surgery was the preferred treatment but the patients were considered unlit for a resection on the grounds of age or poor medical condition. Two other patients with T3 tumours refused surgery. The sites and stage of the primary tumours is shown in Table 1. Thirty-three patients were treated solely by iridium wire implant. The doses given ranged from 60 68 Gray estimated at the reference isodose using the Paris dosimctry system (Pierquin rt al.: 197X). Techniques were as described by Paine (1972). Thirty-four patients were treated by external radiotherapy including the regional lymph nodes in addition to implant: these were patients who were considered to have a high risk of lymphatic spread of the tumour. judged by the size or depth of the lesion or poorly differentiated histology. Also patients considered unlikely to attend regularly for follow-up and consequently unsuitable for a ‘watch’ policy for management of the lymph nodes of the neck received external beam radiotherapy. Table 2 shows the stage of the patients who received external beam therapy. In all but one patient the external radiotherapy was given before implant. A dose of 40 Gray in 20 daily fractions was given to the primary tumour and 50 Gray in 25 fractions to the regional lymph nodes. Two weeks after the end of radiotherapy the implant was performed to deliver a further 25 30 Gray to the primary tumour. Six patients with clinically involved lymph nodes at presentation also underwent neck discction as part of their initial planned treatment.
Table I - Sims and stages (IIICC Site Tongue Floor of mouth Check Total
TI NO 18
TI T2 T3 Total
22 8
18
Table 2 - Methods Stag
T2KO
lntcrstitial Sumber
T3Yl
Total
II
_
4
55
2
_
2
4
IO 2 61
32
II
I I
31
2
survival
Site and stage
Number patisnts
Tongue TI and T2 Tongue T3 Floor of mouth (all T2) Cheek T2
0
rates
I
of
% alive 3 years
5 years
40 I5 IO
67% 37% 100%
60% 37% 70%
2
100%
100%
2
3
4
TIE SINCE FIRST TREATMENT 0 Fig. I - Actuarial survival curves-upper solid line= Tl; broken line=T2: lower solid linc=T3. 95% confidence limits indicated.
and local rccurrcnce
only Recurrence
I4 17 _
Table 3 - Crude
Primary site
T2 NI
_
The crude survival rates by site and stage of disease are shown in Table 3 and Figure 1. Twenty-six patients died within 5 years of treatment. 5 of intercurrent disease. 2 of a second head and neck primary carcinoma and 19 of their oral cancer. The sites of uncontrolled disease at death are shown in Figure 2. All but 3 of the 19 fatal cases had active tumour in the neck at the time of death. The success of treatment of the primary tumour expressed as probability of freedom from local rccurrcncc is shown in Figure 3. At 3 years after treatment the recurrence-free probability was 89% for TI. 85%
treated
T3 NO
2
of treatment
1987) of pammts
RESLT,TS
lntcrstitial + external Number
Recurrence
4 I7 1s 36
I 4 I2 17
Nehk Fig. 2 - Sites
of uncontrolledtumour
metastases at death
5
Interstitial
c
1rn so
Ii
aam-
: t
60 sQ-
J-
1
0
2
3
5
4
TILE SINCE FIRST IRSA?WNT 0 Fig. 3 - Local tumour control by radiation-upper solid line= Tl; broken line = T2: lower solid line = T3. 95% conlidcncc limits indicated.
for T2. and 20% for T3 turnours. Local recurrence occurred in 2 of 18 Tl, five of 34 T2. and 12 of 15 T3 tumours. Surgical salvage was attempted in all the 7 T1 and T2 turnouts which recurred. Five tongue turnouts were removed by hemiglossectomy and 2 floor of mouth tumours by wide excision and repair using a free radial forearm flap. Surgery was succcssful in preventing further local rccurrencc in 6 of these, giving an ultimate failure rate at the primary site of 2%. Of the 12 T3 tumours which recurred. salvage total or sub-total glosscctomy was performed in 7; 2 developed further recurrcncc. Five were unsuitable for surgery because of age or poor general condition. The ultimate failure at the primary site in T3 turnours was 47%“. Patients who had combined external therapy and implant for Tl and T2 tumours had a higher recurrence rate than those treated by implant alone, 5 out of 21 compared with 2 out of 3 I respectively (P < 0.1). Sixty-one patients had no clinical or radiological evidence of lymph node involvement at the time of primary treatment; 22 subsequently developed lymph node metastases. Five were unfit for surgery. Neck dissection was performed in 17; only 4 of these patients wcrc alive and disease-free at 5 years. Nine dcvcloped recurrence in the dissected side of the neck, of whom 4 also had primary recurrence. Two died of contra-lateral nodal metastases. and 2 of pulmonary metastases. Therefore only 4/22 patients (18%) developing neck recurrence were alive at 5 years. Table 4 shows the incidence of nodal metastascs in
TI ‘1‘2 T3 Total
iridium-192
351
relation
0
stage
mine
to T stage and the influence of external of the neck at the time of primary treatthose patients who did not also develop recurrence of the primary turnout-, 2 out of 18 who had had external radiotherapy to the neck developed nodal mctastascs compared with 12 out of 29 who did not have external radiotherapy (p < 0.05 on univariatc analysis). Multivariatc analysis was performed to investigate which prognostic and treatment-related factors were significantly associated with survival. local recurrence, and lymph node recurrence. Few factors reached the 5% significance level because of the small number of patients. For both nodal recurrence and survival these were histology and use of elective neck irradiation. Well-differentiated compared with moderately or poorly diffcrcntiated carcinoma was associated with better survival (hazard ratio 7.25, p= 0.002) and a lower rate of lymph node recurrence (HR 33, p = 0.01). Elective neck irradiation was associated with a higher survival rate (HR= 7.25, p= 0.002), and its effect on reduction of nodal recurrence was confirmed (HR 3.4, p=O.Ol). The significant factors for local recurrence were T-stage (p < 0.001) and age; local recurrence risk was significantly greater in 8 patients under the age of 40 years (p
irradiation lr -TL-l~___~~~~~____~~~~~__~~~~~_------______-_________ment. In
Ill
Table4clinically
irradiation
Incidence of lymph X0 at presentation
node metastases
in patients
staged
Interstitial only Sumber of I.ymph node metastases patients
Interstitial f external Sumber of Lymph node patients metastascs
I4 (13) I7 (16) 31 (29)
I3 (12)
4 (3) I5 (12) 11 (3) 30 (IX)
indicate
those patients
Figures in parenthesis of local rccurrcnce.
8 (7) 5 (5) _
DISCUSSlON This scrics confirms the effectiveness of interstitial irradiation in controlling Tl and T2 primary squamous carcinoma of the oral cavity. The results reported here are similar to those from Europe and North Table 5 - Radiation
I (0) 4 (2) 3 (0) 8 (2) who remained
free
Soft tissue necrosis Majot Minor Total
complications Interstitial only
Interstitial + external
Total
4 9 13
I 7 8
5 I6 21
358
British Journal
of Oral and Maxillofacial
Surgery
America. They arc disappointing for larger tumours which are better treated where possible by radical surgery combined with post-operative radiotherapy. Iridium wire has proved easier and safer to handle than radium or caesium needles: with a consequent improvement in treatment results. Pierquin (1970) reported an improvement in local control of Tl and T2 oral carcinoma from 60-96X when he changed from using radium needles to iridium wires. In tongue and floor of mouth tumours of the same stage at the Royal Marsdcn Hospital over a l6-year-period the success rate of iridium wires was 82% compared with 65% using caesium needles (Dearnalcy et uf.. 1991) (p =0.08 on multivariatc analysis). The report of Dcarnaley et uf. contained results of IO patients treated with l92-Ir implantation as a pilot study by another clinician in 1971-2. These IO patients are not included in this report, which concentrates on those patients with oral cavity carcinoma treated with l92-Ir from 1977 to the end of 1986, and reflects current practice in this Unit. Fifty-seven patients are included in both reports. The morbidity of interstitial irradiation is low. Small soft tissue necrotic ulcers occur not infrequently but heal after treatment. The lack of osteoradionccrosis in this series reflects the value of collaboration with an oral surgeon and the importance of good dental care (Calman & Langdon, 1991). The functional results were excellent; all the patients cured of their tumours have normal speech and swallowing and the teeth were preserved in dentate patients. This series provides further evidence that failure to control lymphatic spread in the neck is the major cause of death from oral cancer. The value of elective treatment of the clinically negative neck (Million, 1974) remains controversial; two small controlled trials failed to show a survival advantage either from et ul., 1980) elective neck dissection (Vandenbrouck or from elective neck irradiation (Pointon & Cleave. 1990). However multi-variate analysis of prognostic factors suggests a survival benefit for elective irradiation, as was shown in a previous report from this hospital (Dearnaley et al., 1991). while a similar benefit of elective neck dissection was seen in a large retrospective series reported by Piedbois e’t ul. (1991). In this series elective neck irradiation achieved a significant reduction in the incidence of neck metastascs in those patients in whom the primary tumour was controlled, despite the fact that irradiation was chosen for those patients at greatest risk of lymph node metastases. Patients who developed nodal mctastases had a poor prognosis. Therefore an aggressive approach to the management of neck nodes seems justified. It has been shown that when external and interstitial irradiation are combined the lower the proportion of dose from the interstitial component the higher is the failure rate at the primary site (Wendt et al., 1990). In this series the combined treatment was given to patients with more aggressive disease, and was associated with a 17% lower success rate, but with less morbidity. The difference in outcome was not significant on either univariate or multivariate
analysis, so it is doubtful if combining external and interstitial irradiation prejudiced the success of trcatmcnt of the primary. The relative success of the combined method compared with other series may be explained by the short interval between external and interstitial treatment, keeping the total time below 7 weeks (Mendenhall et NI., 1982). Referrals of oral cancer for interstitial irradiation have declined in number in the past few years. Many of the patients included in this report would now bc treated by primary surgery. The reasons are two-fold. Firstly the results of radiotherapy in the UK are generally unsatisfactory, partly because of radiotherapists’ reluctance to USC interstitial irradiation or to refer patients to centres specialising in the technique. Secondly, newer surgical reconstructive techniques give excellent restoration of anatomy so that surgical morbidity is less than previously. Nevertheless some palicnts still have difficulty adjusting to the lack of innervation of the replaced tissues in the mouth with consequent problems with speech and swallowing. Assessments of quality of life have suggested greater impairment in patients treated by surgery compared to patients treated by radiotherapy alone (Morton et al., 1984; Rathmell et al., 1991). while there is as yet no evidence that surgical treatment of the primary leads to higher survival rates than interstitial irradiation. In fact, comparison of incidence in relation to death rates for the 1960s and 1980s show that the cure rates of oral cancer in the UK arc not improving, maybe even deteriorating (Hindle & Nally, 1991). In the short term, prospects for improving survival rates lie with earlier diagnosis and more appropriate selection of treatment. To achieve the latter, prospective controlled trials between surgery and irradiation are the ideal, but are not practicable because of the hctcrogeneity of the disease and the large numbers of patients required. However: retrospective reviews with multivariate analysis of prognostic factors can be used to demonstrate differences in treatment outcome, and should be encouraged. In the future it may become possible to predict the radiocurability of a tumour from a biopsy, so that appropriate treatment can bc designed for the individual patient. Even soI the fate of the patient will probably be determined more by the management of the neck than by the choice of treatment of the primary. Meanwhile oral cancer patients should be managed by multi-disciplinary teams and thoroughly documented.
Acknowledgements I am grateful to the surgeons who referred the patients included in this report. I would like to thank Mr R. A’IIern for the statistical analysis, and Mrs V. Michelmore for typing the manuscript.
References Cade, S. & Lee, E. S. (1957). Cancer of .surgPr~. 187,433.
of the tongue.
Brirish
Journd
Interstitial
irradiation
using iridium-192
359
Calman. F. & Langdon, J. D. (1991). Oral complications ofcancer. Brirish Medical Journul. 302, 485. Dearnalcq. D.: Dardoufas. C., A’Hcrn, R. P. & Ilcnk, J. .M. (19Yi). lntcrstitial irradiation for carcinoma of the tongue and floor of mouth: Roval Marsdcn Hospital expcricncc 1970 1986. Rudiotherap~~and Oncolog_y, 2i, 183. . DCCroix, Y. & Ghossein. N. A. (1981). Expcricnce of the Curie Institute in treatment ofcancer of the mobile tongue. Cancer. 47,496. Hall, E. J. (1977). The OER at low dose rates. British Jowmtl ftf RodiologJ;. 30, 373. Hindle. I. & Nally. F. (1991). Oral cancer: a comparative study bctwccn 1962 67 and 1980-84 in England and Wales. Bri/ish Dcnrul Journal. 170, 15. McGregor. A. D. (1989). Management of intra-oral squamous ccl1 carcinoma. Journal of the Ro.val Socieiy q/ Medicinr. 82, 187. Mendcnhall, W. M.: Steed van Cisc, W.. Boba. F. J. & Million: R. R. (1982). Analysis of time-dose factors in squamous ccl1 carcinoma of the oral ton_euc and lloor of mouth treated with radiation therapy alone. Inrernationul Journul of Radiation Oncolog), Biology Physic.7. 7, 1005. Million. R. R. (IY74). Elcctivc neck irradiation for TX NO squamous carcinoma of the oral tongue and floor of mouth. Cunwr, 34, 149. Morris, S. (1970). A seven-year survey of changing treatment in carcinoma of the tongue. C/inicul Radiology, 21,431. Morton, R. P.. Davies. A. I>. M., Baker. J.. Baker, G. A. & Stcll, I’. M. (1984). Quality of lift in treated head and neck cancel patients: a preliminary report. Clinical Orolutyngolog~. 9, 181. Paine. C. 11. (1972). Modern after-loading methods for interstitial radiotherapy. Clinical Radiology, 23, 262. Picdbois. P.. MaLeron. J-J., Haddad, E.. Costc, A., Martin. M., Levy, C., Raynal, M., Pavlovitch, J. M., Pcyncgrc, R.. Picrquin. 13. & 1.e Bourgeois, J. P. (1991). Stage I II squamous cell carcinoma of the oral cavity trcatcd by iridium192: is elective neck dissection indicated? Radiorherup); und
(1978). The Paris system in interstitial radiation therapy. Acru Rudiologica Oncology, 17, 33. Pointon, R. C. S. & Gleave, E. N. (1990). Lymphatic spread. In: 7ieurtnenr qf Cancer. 2nd cd.. K. Sikora and K. E. Halnan (eds.). London: Chapman and Hall. Rathmcll. A. J.. Ash. D. V.. Howes. M. & Nicholls. J. (199 1). Assessing quality of lift in patients treated for advanced head and neck cancer. Clinicul Oncology. 3, 10. Vandcnbrouck. C.. Sancho-Gamier, II.. Chassagne. D.. Saravaanc. D.. Cachin. Y. & Michaeu. C. (1980). Elective versus therapeutic radical neck dissection in epidcrmoid carcinoma of the oral cavity. C‘uncrr, 46,386. Wallner. P. E.: Ilanks. G. E., Kramer. S. & McLean, C. J. (1986). Patterns of care study: analysis of outcome survey dataanterior two-thirds of tongue and floor of mouth. American Journul ofClinical Oncology, 9,50. Wcndt. C. D., Peters. L. J.. Delclos, L.. Ang, K. K.. Morrison. W. H.. Maor: M. II.. Robbins. K. T.. Byers. R. M.. Carlson. L. S. & Oswald, M. J. (I 990). Primary radiotherapy in the treatment of stage I and II oral tongue cancers: importance of the proportion of therapy delivered with interstitial therapy. Internotional Journal of Radiation Oncolog): Uiobgy Physics, 18, 1287. Withers. II. R.. Taylor. J. M. G. & Maciejewski, B. (1988). The hazard of accelerated tumour clonogcn repopulation during radiotherapy. Acru Oncologicu, 27, I3 I.
Picruuin. B.. Chassaene. D.. Cachin. Y.. Baillet. F. & Fournelle le ‘Buis, 1:: (lY70).?arcinomcs epidermoides de la langue mobile et du plancher buccal. Actu Rudiologira Therupy. 9,465. Pierquin. B., Dutreix, A.. Paine. C. H.. Marinello. G. &Ash, D.
Correspondence
The Author .J. M. Henk F’KCW Consultant Radiotherapist Head and Neck Unit Royal Mars&n Hospital Fulham Road London SW3 6JJ
and Oncologist
and requests
Paper received 5 March Accepted 15 June 1992
1992
for ofl’prints to Dr J. M. Henk
oi Oral
and
i lW2)
30. 355-359
I
r
Treatment of oral cancer by interstitial irradiation using iridium-192 J. M. Henk
SG’MM/I R Y. Sixty-seven patients with squamous cell carcinoma of the oral cavity were treated by implantation of radio-active iridium wire between 1977 and 1986. The results are presented in the hope of providing a comparison with those of primary surgical management. The crude 5-year survival rates were 61% for Tl, 74% for T2, and 37% for T3 tumours. The major causes of death were uncontrolled tumour in the neck and intercurrent disease. Seven of 52 patients with Tl or T2 tumours (13%) developed local recurrence at the primary site; five were salvaged surgically, for an ultimate failure rate of 4%. The ultimate failure for a group of 15 ‘~3 tumours was 47%. The only morbidity was a 31% incidence of soft tissue ulcers occurring during the first 18 months after treatment, none of which persisted. Elective external beam radiotherapy to the clinically negative neck significantly reduced the incidence of overt lymph node metastases.
INTRODL:CTlON
1977). Several studies have demonstrated superior results from interstitial compared with external irradiation (Wallner et al., 1986; Wendt et al., 1990). In the past 1.5 years. as better reconstructive techniques have been developed, surgery has become increasingly popular as the primary treatment for cancer so that the use of interstitial irradiation has declined. Some surgeons now maintain that most mouth cancers should be treated surgically, and that the only indication for radiotherapy is external beam post-operatively (McGregor. 1989). Thcrc is little dcbatc that surgery is the trcatmcnt of choice for very small lesions which can be easily excised with primary closure: or that advanced tumours infiltrating bone or deeply into muscle require surgery usually with post-opcrativc radiotherapy. However there is an intcrmcdiatc group consisting of the larger Tl and T2 and some earlier exophytic T3 tumours in which the relative merits of primary treatment by surgery or by radiotherapy remain debatable. As a consequence of the results of Pierquin et al (1970) which showed markedly bcttcr results from the use of iridium compared with radium, iridium wire implantation was introduced as a standard method of irradiation of oral cancer at the Royal Marsdcn Hospital in 1977. The results of the first 8 years experience are reviewed here, because although the technique is fairly widely used there is little information on the results obtained in the UK. It is hoped that the survival, local recurrcncc and morbidity rates reported here will provide a background for comparison with results of the newer surgical techniques.
Interstitial implantation of radio-active material has been a treatment option for oral cancer for 70 years. When the method was first introduced the only radioactive substances available were those occurring naturally i.e. radium and its daughter gaseous product radon. In the period before the Second World War the incidence of mouth cancer in the UK was considcrably higher than it is now. Radium nccdlcs wcrc used extensively cspccially for tongue cancer; surgeons were skilled in their use and results were generally good (Cade & Lee. 1957; De Croix & Ghosscin, 198 I). After the Second World War the hazards to staff from the use of radium became more apparent. At the same time supcrvoltagc external beam radiotherapy was being dcvcloped, so radium needling declined in popularity. However, the results of external beam irradiation proved disappointing (Morris. 1970) and the advent of new artificially-produced radio-active materials. cspccially caesium-I 37 and iridium-192. led to a renaissance of interstitial radiotherapy in the 1970’s (Paine. 1972). Interstitial irradiation is a suitable treatment for oral cancer provided the soft tissues are mobile and the tumour is at least 5 mm clear of adjacent bone. In such situations interstitial irradiation has considcrable biological advantages over external irradiation. The radiation from interstitial sources is delivered in a high dose to the vicinity of the tumour with minimal dosage to surrounding structures, therefore xcrostomia is not a sequel. Treatment is delivered over a few days, so that there is less tumour cell repopulation during treatment than in the case of external radiotherapy (Withers et al.. 1988) Also, the radiation is delivered continuously, at a low dose-rate, under which conditions hypoxic tumour cells may be less radio-resistant (Hall.
PATIENTS
AND METHODS
From 1977 through 1986. 67 patients with squamous carcinoma of the oral cavity were trcatcd by radical 355
356
British Journal
of Oral and Maxillofacial
Sureer\;
radiotherapy using iridium-192 implantation either alone or in combination with external radiotherapy. Forty-eight were male and 19 female. The median age was 63 years, the range 26-89 years. The choice of treatment policy between elective surgery or radical radiotherapy with surgery reserved for salvage was made at joint consultation bctwccn a surgcon and a radiotherapist. The reason for preferring radiotherapy in most of these patients was that it was considered likely to give a better functional result than surgery with an equal chance of survival. In 5 patients with advanced (T3) tumours surgery was the preferred treatment but the patients were considered unlit for a resection on the grounds of age or poor medical condition. Two other patients with T3 tumours refused surgery. The sites and stage of the primary tumours is shown in Table 1. Thirty-three patients were treated solely by iridium wire implant. The doses given ranged from 60 68 Gray estimated at the reference isodose using the Paris dosimctry system (Pierquin rt al.: 197X). Techniques were as described by Paine (1972). Thirty-four patients were treated by external radiotherapy including the regional lymph nodes in addition to implant: these were patients who were considered to have a high risk of lymphatic spread of the tumour. judged by the size or depth of the lesion or poorly differentiated histology. Also patients considered unlikely to attend regularly for follow-up and consequently unsuitable for a ‘watch’ policy for management of the lymph nodes of the neck received external beam radiotherapy. Table 2 shows the stage of the patients who received external beam therapy. In all but one patient the external radiotherapy was given before implant. A dose of 40 Gray in 20 daily fractions was given to the primary tumour and 50 Gray in 25 fractions to the regional lymph nodes. Two weeks after the end of radiotherapy the implant was performed to deliver a further 25 30 Gray to the primary tumour. Six patients with clinically involved lymph nodes at presentation also underwent neck discction as part of their initial planned treatment.
Table I - Sims and stages (IIICC Site Tongue Floor of mouth Check Total
TI NO 18
TI T2 T3 Total
22 8
18
Table 2 - Methods Stag
T2KO
lntcrstitial Sumber
T3Yl
Total
II
_
4
55
2
_
2
4
IO 2 61
32
II
I I
31
2
survival
Site and stage
Number patisnts
Tongue TI and T2 Tongue T3 Floor of mouth (all T2) Cheek T2
0
rates
I
of
% alive 3 years
5 years
40 I5 IO
67% 37% 100%
60% 37% 70%
2
100%
100%
2
3
4
TIE SINCE FIRST TREATMENT 0 Fig. I - Actuarial survival curves-upper solid line= Tl; broken line=T2: lower solid linc=T3. 95% confidence limits indicated.
and local rccurrcnce
only Recurrence
I4 17 _
Table 3 - Crude
Primary site
T2 NI
_
The crude survival rates by site and stage of disease are shown in Table 3 and Figure 1. Twenty-six patients died within 5 years of treatment. 5 of intercurrent disease. 2 of a second head and neck primary carcinoma and 19 of their oral cancer. The sites of uncontrolled disease at death are shown in Figure 2. All but 3 of the 19 fatal cases had active tumour in the neck at the time of death. The success of treatment of the primary tumour expressed as probability of freedom from local rccurrcncc is shown in Figure 3. At 3 years after treatment the recurrence-free probability was 89% for TI. 85%
treated
T3 NO
2
of treatment
1987) of pammts
RESLT,TS
lntcrstitial + external Number
Recurrence
4 I7 1s 36
I 4 I2 17
Nehk Fig. 2 - Sites
of uncontrolledtumour
metastases at death
5
Interstitial
c
1rn so
Ii
aam-
: t
60 sQ-
J-
1
0
2
3
5
4
TILE SINCE FIRST IRSA?WNT 0 Fig. 3 - Local tumour control by radiation-upper solid line= Tl; broken line = T2: lower solid line = T3. 95% conlidcncc limits indicated.
for T2. and 20% for T3 turnours. Local recurrence occurred in 2 of 18 Tl, five of 34 T2. and 12 of 15 T3 tumours. Surgical salvage was attempted in all the 7 T1 and T2 turnouts which recurred. Five tongue turnouts were removed by hemiglossectomy and 2 floor of mouth tumours by wide excision and repair using a free radial forearm flap. Surgery was succcssful in preventing further local rccurrencc in 6 of these, giving an ultimate failure rate at the primary site of 2%. Of the 12 T3 tumours which recurred. salvage total or sub-total glosscctomy was performed in 7; 2 developed further recurrcncc. Five were unsuitable for surgery because of age or poor general condition. The ultimate failure at the primary site in T3 turnours was 47%“. Patients who had combined external therapy and implant for Tl and T2 tumours had a higher recurrence rate than those treated by implant alone, 5 out of 21 compared with 2 out of 3 I respectively (P < 0.1). Sixty-one patients had no clinical or radiological evidence of lymph node involvement at the time of primary treatment; 22 subsequently developed lymph node metastases. Five were unfit for surgery. Neck dissection was performed in 17; only 4 of these patients wcrc alive and disease-free at 5 years. Nine dcvcloped recurrence in the dissected side of the neck, of whom 4 also had primary recurrence. Two died of contra-lateral nodal metastases. and 2 of pulmonary metastases. Therefore only 4/22 patients (18%) developing neck recurrence were alive at 5 years. Table 4 shows the incidence of nodal metastascs in
TI ‘1‘2 T3 Total
iridium-192
351
relation
0
stage
mine
to T stage and the influence of external of the neck at the time of primary treatthose patients who did not also develop recurrence of the primary turnout-, 2 out of 18 who had had external radiotherapy to the neck developed nodal mctastascs compared with 12 out of 29 who did not have external radiotherapy (p < 0.05 on univariatc analysis). Multivariatc analysis was performed to investigate which prognostic and treatment-related factors were significantly associated with survival. local recurrence, and lymph node recurrence. Few factors reached the 5% significance level because of the small number of patients. For both nodal recurrence and survival these were histology and use of elective neck irradiation. Well-differentiated compared with moderately or poorly diffcrcntiated carcinoma was associated with better survival (hazard ratio 7.25, p= 0.002) and a lower rate of lymph node recurrence (HR 33, p = 0.01). Elective neck irradiation was associated with a higher survival rate (HR= 7.25, p= 0.002), and its effect on reduction of nodal recurrence was confirmed (HR 3.4, p=O.Ol). The significant factors for local recurrence were T-stage (p < 0.001) and age; local recurrence risk was significantly greater in 8 patients under the age of 40 years (p
irradiation lr -TL-l~___~~~~~____~~~~~__~~~~~_------______-_________ment. In
Ill
Table4clinically
irradiation
Incidence of lymph X0 at presentation
node metastases
in patients
staged
Interstitial only Sumber of I.ymph node metastases patients
Interstitial f external Sumber of Lymph node patients metastascs
I4 (13) I7 (16) 31 (29)
I3 (12)
4 (3) I5 (12) 11 (3) 30 (IX)
indicate
those patients
Figures in parenthesis of local rccurrcnce.
8 (7) 5 (5) _
DISCUSSlON This scrics confirms the effectiveness of interstitial irradiation in controlling Tl and T2 primary squamous carcinoma of the oral cavity. The results reported here are similar to those from Europe and North Table 5 - Radiation
I (0) 4 (2) 3 (0) 8 (2) who remained
free
Soft tissue necrosis Majot Minor Total
complications Interstitial only
Interstitial + external
Total
4 9 13
I 7 8
5 I6 21
358
British Journal
of Oral and Maxillofacial
Surgery
America. They arc disappointing for larger tumours which are better treated where possible by radical surgery combined with post-operative radiotherapy. Iridium wire has proved easier and safer to handle than radium or caesium needles: with a consequent improvement in treatment results. Pierquin (1970) reported an improvement in local control of Tl and T2 oral carcinoma from 60-96X when he changed from using radium needles to iridium wires. In tongue and floor of mouth tumours of the same stage at the Royal Marsdcn Hospital over a l6-year-period the success rate of iridium wires was 82% compared with 65% using caesium needles (Dearnalcy et uf.. 1991) (p =0.08 on multivariatc analysis). The report of Dcarnaley et uf. contained results of IO patients treated with l92-Ir implantation as a pilot study by another clinician in 1971-2. These IO patients are not included in this report, which concentrates on those patients with oral cavity carcinoma treated with l92-Ir from 1977 to the end of 1986, and reflects current practice in this Unit. Fifty-seven patients are included in both reports. The morbidity of interstitial irradiation is low. Small soft tissue necrotic ulcers occur not infrequently but heal after treatment. The lack of osteoradionccrosis in this series reflects the value of collaboration with an oral surgeon and the importance of good dental care (Calman & Langdon, 1991). The functional results were excellent; all the patients cured of their tumours have normal speech and swallowing and the teeth were preserved in dentate patients. This series provides further evidence that failure to control lymphatic spread in the neck is the major cause of death from oral cancer. The value of elective treatment of the clinically negative neck (Million, 1974) remains controversial; two small controlled trials failed to show a survival advantage either from et ul., 1980) elective neck dissection (Vandenbrouck or from elective neck irradiation (Pointon & Cleave. 1990). However multi-variate analysis of prognostic factors suggests a survival benefit for elective irradiation, as was shown in a previous report from this hospital (Dearnaley et al., 1991). while a similar benefit of elective neck dissection was seen in a large retrospective series reported by Piedbois e’t ul. (1991). In this series elective neck irradiation achieved a significant reduction in the incidence of neck metastascs in those patients in whom the primary tumour was controlled, despite the fact that irradiation was chosen for those patients at greatest risk of lymph node metastases. Patients who developed nodal mctastases had a poor prognosis. Therefore an aggressive approach to the management of neck nodes seems justified. It has been shown that when external and interstitial irradiation are combined the lower the proportion of dose from the interstitial component the higher is the failure rate at the primary site (Wendt et al., 1990). In this series the combined treatment was given to patients with more aggressive disease, and was associated with a 17% lower success rate, but with less morbidity. The difference in outcome was not significant on either univariate or multivariate
analysis, so it is doubtful if combining external and interstitial irradiation prejudiced the success of trcatmcnt of the primary. The relative success of the combined method compared with other series may be explained by the short interval between external and interstitial treatment, keeping the total time below 7 weeks (Mendenhall et NI., 1982). Referrals of oral cancer for interstitial irradiation have declined in number in the past few years. Many of the patients included in this report would now bc treated by primary surgery. The reasons are two-fold. Firstly the results of radiotherapy in the UK are generally unsatisfactory, partly because of radiotherapists’ reluctance to USC interstitial irradiation or to refer patients to centres specialising in the technique. Secondly, newer surgical reconstructive techniques give excellent restoration of anatomy so that surgical morbidity is less than previously. Nevertheless some palicnts still have difficulty adjusting to the lack of innervation of the replaced tissues in the mouth with consequent problems with speech and swallowing. Assessments of quality of life have suggested greater impairment in patients treated by surgery compared to patients treated by radiotherapy alone (Morton et al., 1984; Rathmell et al., 1991). while there is as yet no evidence that surgical treatment of the primary leads to higher survival rates than interstitial irradiation. In fact, comparison of incidence in relation to death rates for the 1960s and 1980s show that the cure rates of oral cancer in the UK arc not improving, maybe even deteriorating (Hindle & Nally, 1991). In the short term, prospects for improving survival rates lie with earlier diagnosis and more appropriate selection of treatment. To achieve the latter, prospective controlled trials between surgery and irradiation are the ideal, but are not practicable because of the hctcrogeneity of the disease and the large numbers of patients required. However: retrospective reviews with multivariate analysis of prognostic factors can be used to demonstrate differences in treatment outcome, and should be encouraged. In the future it may become possible to predict the radiocurability of a tumour from a biopsy, so that appropriate treatment can bc designed for the individual patient. Even soI the fate of the patient will probably be determined more by the management of the neck than by the choice of treatment of the primary. Meanwhile oral cancer patients should be managed by multi-disciplinary teams and thoroughly documented.
Acknowledgements I am grateful to the surgeons who referred the patients included in this report. I would like to thank Mr R. A’IIern for the statistical analysis, and Mrs V. Michelmore for typing the manuscript.
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Correspondence
The Author .J. M. Henk F’KCW Consultant Radiotherapist Head and Neck Unit Royal Mars&n Hospital Fulham Road London SW3 6JJ
and Oncologist
and requests
Paper received 5 March Accepted 15 June 1992
1992
for ofl’prints to Dr J. M. Henk