Int. J. Radinfion Oncology Biof. Phgs.. Vol. 5. pp. 515-519 @ Pergamon Press Ltd., 1979. Printed in the U.S.A.
0360-3016/79/0401-0515/W2.00/0
??Brief Communication
POSTOPERATIVE CELL
SPLIT COURSE RADIOTHERAPY OF SQUAMOUS CARCINOMA OF THE ORAL TONGUE
MICHAEL
BAMBERG,
M.D.,
and EBERHARD
ULRICH SCHULZ, M.D.
SCHERER, M.D.?
Forty nine patients with squamous cell carcinoma of the oral tongue were irradiated postoperatively using a split course technique for external irradiation alone or in combination with intraoral cone X-ray therapy. After a 3 year follow-up the results of local control were compared with those of other authors, who irradiated initially with combined external and interstitial therapy in one series. For two series the nominal standard dose (NSD)was calculated with the modified Ellis formula given by Gabriel-Jirgens ef af.” and Gremmel et aL” In our patient collective the recurrence rate was higher in the early T-stages, because the dosage applied was lower than in the majority of the cited publications. The combined modality of surgery and following external irradiation could not improve the outstanding results of interstitial therapy in Tl and T2 tumors. When the split course technique is used, the total dose and treatment time must be increased to obtain the same local control rate as in one series irradiation. Especially in advanced cases the split dose regimen seems to be an alternative treatment, because severe complications were not observed in our patients. For split course therapy we recommend the application of 1700 ret for Stage Tl oral tongue carcinoma 1800 ret for Stage T2 and 1900 ret for T3 tumors. For treatment of recurrences, surgery appears to be superior to irradiation. Squamous
cell carcinoma,
Oral tongue, Split-course therapy, Combined
INTRODUCTION
patients with well differentiated squamous cell carcinoma of the tongue were treated at the Department of Radiology, University of Essen (Table 1). All of them were followed for a minimum of 3 years. Patients with previous radiation treatment or recurrent disease were excluded from this study. There were 32 males and 17 females, a male to female ratio of approximately 2 to 1. Thirty one (63.2%) of the patients were between 50 and 70 years of age. The youngest patient was 25 years old and the oldest 85. The stagingj: for the primary lesion is as follows:3,4 Tl = Tumors less than 2 cm in diameter. T2 = Tumors 24 cm in diameter, limited invasion of surrounding structures. T3 = Tumors more than 4 cm in diameter, or having invasion of surrounding structures (periosteal involvement = “pressure” defect in bone), or both. T4 = Massive tumor or bone invasion.
Radiotherapy for well differentiated squamous cell carcinoma of the oral tongue can be carried out as external irradiation, interstitial irradiation or various combinations thereof. Damage to the mucous membrane of the oral cavity is nearly impossible to avoid; however, it can be diminished by split course therapy without reducing its effectiveness.‘3.‘8 This study deals with the postoperative results of teletherapy alone or in combination with intraoral X-ray therapy, using a split course technique. It is our purpose, to analyze the failures at the primary site as related to T-stage, modality of irradiation and nominal standard dose.5~7,‘0~”
METHODS
From
1 January
AND
1968 to
MATERIALS
31 December
modalities.
1973, 49
tProfessor and Chief, Department of Radiotherapy *Presented at the 57th annual meeting of the American Radium Society, Isla Verde, Puerto Rico, 4-9 May 1975. Reprint requests to: Michael Bamberg, M.D., Department
of Radiology, West German Tumor Center, Essen, Federal Republic of Germany. Accepted for publication 4 January 1979. 515
University
of
516
Table
Stage
Radiation Oncology 0 Biology 0 Physics
1. Incidence
of local recurrence T-stage of disease
No. of patients
in correlation
No. of recurrences
April 1979, Volume 5, Number 4
to
(%)
Tl T2 T3 T4
9 19 18 3
3 6 5 1
(33.3) (31.5) (27.7) (33.3)
Total
49
15
(30.6)
METHODS
8rbcn?
Surgery was the initial treatment for all patients. Small lesions of TllT2 stage in 28 patients were simply excised. Partial glossectomy and excision of the involved surrounding tissue were performed in 15 patients with advanced tumors. The remaining 6 were treated radically with partial glossectomy and partial resection of the mandible and floor of the mouth. After a post-operative interval of approximately 4 weeks, the surgically treated area and the regional lymph nodes were irradiated with telecobalt or telecesium opposing fields. This external irradiation was delivered at 800-900 rad per week in 5 fractions to a tumor dose of 2500-3500 rad in 3-4 weeks. After an interval of 2-3 weeks, the radiotherapy was continued by intraoral cone therapy (19 patients) or teletherapy with cesium or electrons given through an additional portal (30 patients) to a total dose of 5500-7000 rad. The smaller “tumors” were treated as illustrated in “Advanced primaries” were irradiated by Fig. 1.
------.____
_____------
Cdcm‘ 00 36cm
Fig. 2. Irradiation of T3 tongue carcinoma with Telecesium- 137 “Triple-field” technique. Tumor dose = 6400rad; Field I = 10 x 8.5 cm*, 3000rad; Field II = 8 ~6cm*, 25OOrad; Field III = 6 x4cm2, 9OOrad; FSD= focal skin distance.
telecesium weighting
“triple field” of dose (Fig. 2).
technique
with
unequal
RESULTS
Within a follow-up period of at least 3 years, 15 (30.6%) local recurrences appeared, 10 of them during the first 2 years. Their relationship to primary tumor size is shown in Table 1. A recurrence rate of approximately 30% was found in all stages. By conversion to nominal standard dose (NSD)6.‘0.” 12 recurrences were observed at doses between 1200 and 1700 ret in 29 patients, who received less than 1800 ret. This is a recurrence rate of 41.4%. Two of these patients with primary tumors Stages T2 and T3 died respectively 6 and 8 months after radiotherapy; no local control could be attained. Three local failures, ranging from 1800 to 1920 ret, developed in 20 patients after treatment with more than 1800 ret, a recurrence rate of 15.0%. Severe complications like osteoradionecrosis were not encountered in this split course series, not even above 2000 ret (Table 2). Nine patients with recurrences were irradiated for a second time. This treatment was effective in 3 of 5 cases of Tl/T2 tumors but failed in 4 patients with primary T3 stage lesions. Surgical treatment of recurrences was successful in all three patients (Table
.:::p yz&Jy ......
’
:.a. ,....
9racm2 SSo=Cocm ----me_____
FSD4Ocm
104.
9xtkrd SSD =6Ocm
_______-------
sxacd
Fsomoc~
Fig. 1. Irradiation of T2 tongue carcinoma with “Co parallel opposing fields and a submental field with 20 MeV electrons. Tumor dose = 7200 rad; 6oCo fields = 9 x 8 cm’, 4400 rad; electron fields = 6 x 8 cm’, 2800 rad; tumor = a; maxillary and mandibular region = m9; Or = orbital region: Sm = maxillar sinus; SSD = source skin distance; FSD = focal skin distance.
3). DISCUSSION Sex and age distribution in our patients are similar to data found most frequently in the literature.2.9 Because of variation in the classification used, tumor stage and treatment results are often difficult to
Postoperative
split course radiotherapy
Table 2. Correlation
of squamous
cell carcinoma
of the oral tongue 0
of T-stage of primary tumor, local recurrence
No. of recurrences
No. of T2 patients
No. of T3 patients
No. of recurrences
M. BAMBERC et al
517
and radiation dose
No. of recurrences
No. of T4 patients
No. of recurrences
Ret.
No. of Tl patients
120@-1399 1400-1599 1600-1799 1800-1999 2000-2199
1 2 4 2 0
0 2 I 0 0
5 4 5 4 1
2 1 2 1 0
1 3 4 6 4
1 1 2 1 0
0 0 0 2 1
0 0 0 1 0
Total
9
3
19
6
18
5
3
1
compare.
In contrast
to the patient
collective
from
Chu’ and Fletcher3 and Delclos et ~l.,~ who employed the same staging method, the recurrence rate in Stage T1/7’2 of our collective was higher (Table 4). Both authors treated the smaller tumors initially with a combination of interstitial and external irradiation whereas our patients received intraoral cone- and teletherapy after surgery. This combined modality, however, could not achieve the contenting results of irradiation alone as in the early T-stages of the M. D. Anderson series.3,4 In smaller lesion interstitial therapy should be preferred: this allows the application of very large doses in a sharply defined region.’ During intraoral cone therapy, precision of application is diminished, particularly in elderly patients, by movement of the tongue. Following the pioneering efforts from Holthusen,14 Paterson17 and Strandqvist,” the interdependence of control rate and damage rate of surrounding tissue has been investigated by many authors. In order to achieve approximately 90% control in squamous cell
Stage
carcinoma of tonsillar fossa and supraglottical larynx tumors, Fletcher’ recommended 1800 ret for Tl lesions, 1900 ret for T2 and 2000 and more for T3 and T4 tumors. For the same type of tumors in Stage T2/T3 Shukovsky” considers 2000 ret necessary for a local control rate of 85%. Luk and Castroi reported similar results for T 1 carcinoma of the vocal cord. According to the experiences of Spanos et aLm 6000 rad tumor dose in 6 weeks (corresponding to 1758 ret) is necessary for local control of 90% of tongue tumors in Stage T 1, 7500 rad focal dose in 7.5 weeks (2033 ret) for control of more than 80% of T2/T3 tumors. Bedwinek et al.’ pointed out that with megavoltage treatment, focal doses greater than 7000 rad in 7 weeks lead to significantly increased rates of osteonecrosis in squamous cell carcinoma of the oral cavity. Depending
Table 3. Local recurrence
and ultimate failures after external
No. of patients
Recurrences salvaged by external irradiation
Tl T2 T3 T4
9 19 18 3
Total
49
No. of recurrences
upon
stage
and
previous
surgery,
Recurrences salvaged
irradiation
or surgery
Ultimate local failures No. of patients (%)
3
l/2
6t
5$ I
213 014 0
l/l l/l 0 111
l/9 319 5118 o/3
(11.1) (33.3) (27.7) (0)
15
319
313
9149
(18.4)
tGenera1 medical condition of two patients was not suitable for further therapy. SOne patient refused further therapy. Table 4. Local failures in correlation
Stage
Chu and Fletcher3 No. of patients
(%)
Tl T2 T3 T4
3152 17/100 27166 20130
(5.7) (17.0) (41 .O) (67.0)
Total
671248
(27.0)
our
tumor doses ranged from 5500 to 7ooO rad. In contrast to the cited authors,‘,9.‘5.‘9.20who usually irradiated with 1000 rad per week in a single series, our patients
Delclos et aP No. of patients
to T-stage of disease
(So)
Our results No. of patients
(%)
l/l8 6157 6127 0
(5.5) (10.5) (22.2) (0)
319 6119 S/l8 l/3
(33.3) (31.5) (27.7) (33.3)
13/102
(12.1)
15/49
(30.6)
518
Radiation Oncology 0 Biology 0 Physics
April 1979, Volume 5, Number 4
Fig. 3. The nominal standard dose (NSD)S modified by Gabriel-Jurgens et al.” and Gremmel et al.” NSD = Summary of the partial tolerances PTl and PT2 (if the tolerance limitation of the normal tissue is obtained in 2 series); tl = elapsed time in days of the first series; nl = number of fractions of the first series; RBE dl = dose per fraction of the first series; RBE(60Co) = RBE for beam used related to RBE for @‘Cobeam; R = gap time; t2 = elapsed time in days of the second series; n2 = number of fractions of the second series; d2 = dose per fraction of the second series; RBE = Relative biological effectiveness.
were treated by split course technique in 2 series with an interval of 2-3 weeks on the basis of previous reports.‘3~‘8 In order to obtain comparable values we converted our radiation parameters to nominal standard dose (NSD),6 using the formula given by Gabriel-Jiirgens et aI.” and Gremmel et al.” (Fig. 3). Thus, further considerations on the basis of the Ellis formula are related to the application of irregular fractionation modes and two series of radiation therapy. Thereafter it can be shown that our doses were in part substantially lower than those of other authors namely on the average 1640 ret for Tl tumors and 1730 ret for T2/T3 tumors. Million and Zimmermann16 reported a retrospective evaluation of continuous vs split course irradiation techniques in head and neck squamous cell carcinomas. In the advanced cases the results after split course therapy suggested poorer local control, but in these patients major complications could be decreased. The total dose was not increased for the split course group in contrast to the clinical experience of Holsti.13 With the exception of two ulcers in the primary tumor region, no radiation damages after split course were observed with the doses used in our clinic. However, it must be stated, that the low rate of side effects is linked with a higher recurrence rate in
smaller lesions. For the 21 patients with tumors of Stage T3 and T4 there is an overall recurrence rate of 28.5%. Only 15% local failures were seen in 13 patients who received in excess of 1800 ret. These remarkable results-more comparable to the cases of Chu and Fletcher3 and Delclos et al.4-were achieved in a small number of patients with advanced desease without increasing the radiation morbidity. In 89 patients with tumors of Stage Tl-T3, Delclos et ~1.~ noticed 21% soft tissue ulceration and 19% osteoradionecrosis. The local control in this split course series seems to be “dose dependent”, while the incidence of radiation damages can be diminished by split dose approach especially in advanced cases. According to these results and our experiences, we recommended a split course technique to deliver 1700 ret for T 1 tumors (3000 rad in 3 weeks followed by a 2 weeks respite and 3000 rad in 3 weeks again) for tumors in Stages T2 1800 and T3 1900 ret and 3000-3500 rads in 3-3.5 weeks again). Local recurrences were treated either by irradiation or surgery; in our patients it was apparent that the surgical treatment was more successful than irradiation. Whereas Hamberger et al.‘* reported poor prospects of success for both treatment modalities, our results were supported by the experiences and Lee* and Fletcher and Evers.’
of Cade
REFERENCES Bedwinek, J.M., Shukovsky, J., Fletcher, G.H., Daley, T.E.: Osteonecrosis in patients treated with definitive radiotherapy for squamous cell carcinomas of the oral cavity and naso- and oropharynx. Radiology 119: 665667, 1976. Cade, St., Lee, E.St.: Cancer of the tongue-a study based on 653 patients. Br. J. Surg. 44: 433-446, 1957. Chu, A., Fletcher, G.H.: Incidence and causes of failures to control by irradiation the primary lesions in squamous cell carcinoma of the anterior two-thirds of the tongue and floor of mouth. Am. .I. Roentgenol. 117: 502-508, 1973.
4. Delclos, L.R., Lindberg, D., Fletcher, G.H.: Squamous cell carcinoma of the oral tongue and floor of mouth. Am. J. Roentgenol. 126: 223-228, 1976. 5. Ellis, F.: Dose, time and fractionation: a clinical hypothesis. Clin. Radiol. 20: 1-7, 1%9. Ellis, F.: Fractionation and dose-rate. Br. J. Radiol. 36: 153-162, 1%3. Fletcher, G.H.: Clinical dose-response curves of human malignant epithelial tumours. Br. J. Radiol. 46: l-12, 1973. Fletcher, G.H., Evers, W.Th.: Radiotherapeutic management of surgical recurrences and postoperative
Postoperative
residuals
9.
10.
11.
12.
13. 14.
split course radiotherapy
of squamous cell carcinoma
in tumors of the head and neck. Radiology 95: 185-188, 1970. Fu, K., Ray, J.W., Chan, E.K., Phillips, Th.L.: External and interstitial radiation therapy of carcinoma of the oral tongue. Am. J. Roentgenol. 126: 107-115, 1976. Gabriel-Jiirgens, P., Gremmel, H., Wendhausen, H.: Die Entwicklung und Anwendung der Nominal Standard Dose fiir die Toleranzdosis des gesunden Gewebes in der Strahlentherapie. Strahlentherapie 151: 99-l 12. 1976. Gremmel, H., Kellerer, A.M., Wendhausen, H.: Erganzungen zu den Grundlagen und Anwendung der EllisFormel. Strahlentherapie (in press). Hamberger, A.D., Fletcher, G.H., Guillamondegui, O.M., Byers, R.M.: Advanced squamous cell carcinoma of the oral cavity and oropharynx treated with irradiation and surgery. Radiology 119: 433-438, 1976. Holsti, L.R.: Clinical experience with split-course radiotherapy. Radiology 92: 591-S%, 1%9. Holthusen, H.: Erfahrungen tiber die Vertraglichkeitsfiir Rontgenstrahlen grenze und deren Nutzanwendungen zur Verhtitung von Schaden. Strahlen-
of the oral tongue 0 M. BAMBERG et ul.
519
therapie 57: 254-269, 1936. 15. Luk, K.H., Castro, J.R.: Evaluation of the time-dose factors in glottis tumors. Acta Radio/. Ther. 14: 529536, 1975. 16. Million, R.R., Zimmermann, R.C.: Evaluation of University of Florida split-course technique for various head and neck squamous cell carcinomas. Cancer 35: 1533-1536, 1975. 17. Paterson, R.: Studies in optimum dosage. Br. J. Radiol. 298: 505-516, 1952. 18. Scanlon, P.W.: Split-dose radiotherapy: Follow-up in 50 cases. Am. J. Roentgenol. 90: 280-293, 1%3. 19. Shukovsky, L.J.: Dose-time volume relationship in squamous cell carcinoma of the supraglottic larynx. Am. J. Radiol. 108: 27-29, 1970. 20. Spanos, W.J., Shukovsky, L.J., Fletcher, G.H.: Time, dose and tumor volume relationship in irradiation of squamous cell carcinoma of the base of the tongue. Cancer 37: 2591-2599, 1976. 21. Strandqvist, M.: Studien iiber die kumulative Wirkung der Rontgenstrahlen bei Fraktionierung. Acta Radiol. (Stockh.) Suppl. 55: 1944.
0360-3016/79/0401-0515/W2.00/0
??Brief Communication
POSTOPERATIVE CELL
SPLIT COURSE RADIOTHERAPY OF SQUAMOUS CARCINOMA OF THE ORAL TONGUE
MICHAEL
BAMBERG,
M.D.,
and EBERHARD
ULRICH SCHULZ, M.D.
SCHERER, M.D.?
Forty nine patients with squamous cell carcinoma of the oral tongue were irradiated postoperatively using a split course technique for external irradiation alone or in combination with intraoral cone X-ray therapy. After a 3 year follow-up the results of local control were compared with those of other authors, who irradiated initially with combined external and interstitial therapy in one series. For two series the nominal standard dose (NSD)was calculated with the modified Ellis formula given by Gabriel-Jirgens ef af.” and Gremmel et aL” In our patient collective the recurrence rate was higher in the early T-stages, because the dosage applied was lower than in the majority of the cited publications. The combined modality of surgery and following external irradiation could not improve the outstanding results of interstitial therapy in Tl and T2 tumors. When the split course technique is used, the total dose and treatment time must be increased to obtain the same local control rate as in one series irradiation. Especially in advanced cases the split dose regimen seems to be an alternative treatment, because severe complications were not observed in our patients. For split course therapy we recommend the application of 1700 ret for Stage Tl oral tongue carcinoma 1800 ret for Stage T2 and 1900 ret for T3 tumors. For treatment of recurrences, surgery appears to be superior to irradiation. Squamous
cell carcinoma,
Oral tongue, Split-course therapy, Combined
INTRODUCTION
patients with well differentiated squamous cell carcinoma of the tongue were treated at the Department of Radiology, University of Essen (Table 1). All of them were followed for a minimum of 3 years. Patients with previous radiation treatment or recurrent disease were excluded from this study. There were 32 males and 17 females, a male to female ratio of approximately 2 to 1. Thirty one (63.2%) of the patients were between 50 and 70 years of age. The youngest patient was 25 years old and the oldest 85. The stagingj: for the primary lesion is as follows:3,4 Tl = Tumors less than 2 cm in diameter. T2 = Tumors 24 cm in diameter, limited invasion of surrounding structures. T3 = Tumors more than 4 cm in diameter, or having invasion of surrounding structures (periosteal involvement = “pressure” defect in bone), or both. T4 = Massive tumor or bone invasion.
Radiotherapy for well differentiated squamous cell carcinoma of the oral tongue can be carried out as external irradiation, interstitial irradiation or various combinations thereof. Damage to the mucous membrane of the oral cavity is nearly impossible to avoid; however, it can be diminished by split course therapy without reducing its effectiveness.‘3.‘8 This study deals with the postoperative results of teletherapy alone or in combination with intraoral X-ray therapy, using a split course technique. It is our purpose, to analyze the failures at the primary site as related to T-stage, modality of irradiation and nominal standard dose.5~7,‘0~”
METHODS
From
1 January
AND
1968 to
MATERIALS
31 December
modalities.
1973, 49
tProfessor and Chief, Department of Radiotherapy *Presented at the 57th annual meeting of the American Radium Society, Isla Verde, Puerto Rico, 4-9 May 1975. Reprint requests to: Michael Bamberg, M.D., Department
of Radiology, West German Tumor Center, Essen, Federal Republic of Germany. Accepted for publication 4 January 1979. 515
University
of
516
Table
Stage
Radiation Oncology 0 Biology 0 Physics
1. Incidence
of local recurrence T-stage of disease
No. of patients
in correlation
No. of recurrences
April 1979, Volume 5, Number 4
to
(%)
Tl T2 T3 T4
9 19 18 3
3 6 5 1
(33.3) (31.5) (27.7) (33.3)
Total
49
15
(30.6)
METHODS
8rbcn?
Surgery was the initial treatment for all patients. Small lesions of TllT2 stage in 28 patients were simply excised. Partial glossectomy and excision of the involved surrounding tissue were performed in 15 patients with advanced tumors. The remaining 6 were treated radically with partial glossectomy and partial resection of the mandible and floor of the mouth. After a post-operative interval of approximately 4 weeks, the surgically treated area and the regional lymph nodes were irradiated with telecobalt or telecesium opposing fields. This external irradiation was delivered at 800-900 rad per week in 5 fractions to a tumor dose of 2500-3500 rad in 3-4 weeks. After an interval of 2-3 weeks, the radiotherapy was continued by intraoral cone therapy (19 patients) or teletherapy with cesium or electrons given through an additional portal (30 patients) to a total dose of 5500-7000 rad. The smaller “tumors” were treated as illustrated in “Advanced primaries” were irradiated by Fig. 1.
------.____
_____------
Cdcm‘ 00 36cm
Fig. 2. Irradiation of T3 tongue carcinoma with Telecesium- 137 “Triple-field” technique. Tumor dose = 6400rad; Field I = 10 x 8.5 cm*, 3000rad; Field II = 8 ~6cm*, 25OOrad; Field III = 6 x4cm2, 9OOrad; FSD= focal skin distance.
telecesium weighting
“triple field” of dose (Fig. 2).
technique
with
unequal
RESULTS
Within a follow-up period of at least 3 years, 15 (30.6%) local recurrences appeared, 10 of them during the first 2 years. Their relationship to primary tumor size is shown in Table 1. A recurrence rate of approximately 30% was found in all stages. By conversion to nominal standard dose (NSD)6.‘0.” 12 recurrences were observed at doses between 1200 and 1700 ret in 29 patients, who received less than 1800 ret. This is a recurrence rate of 41.4%. Two of these patients with primary tumors Stages T2 and T3 died respectively 6 and 8 months after radiotherapy; no local control could be attained. Three local failures, ranging from 1800 to 1920 ret, developed in 20 patients after treatment with more than 1800 ret, a recurrence rate of 15.0%. Severe complications like osteoradionecrosis were not encountered in this split course series, not even above 2000 ret (Table 2). Nine patients with recurrences were irradiated for a second time. This treatment was effective in 3 of 5 cases of Tl/T2 tumors but failed in 4 patients with primary T3 stage lesions. Surgical treatment of recurrences was successful in all three patients (Table
.:::p yz&Jy ......
’
:.a. ,....
9racm2 SSo=Cocm ----me_____
FSD4Ocm
104.
9xtkrd SSD =6Ocm
_______-------
sxacd
Fsomoc~
Fig. 1. Irradiation of T2 tongue carcinoma with “Co parallel opposing fields and a submental field with 20 MeV electrons. Tumor dose = 7200 rad; 6oCo fields = 9 x 8 cm’, 4400 rad; electron fields = 6 x 8 cm’, 2800 rad; tumor = a; maxillary and mandibular region = m9; Or = orbital region: Sm = maxillar sinus; SSD = source skin distance; FSD = focal skin distance.
3). DISCUSSION Sex and age distribution in our patients are similar to data found most frequently in the literature.2.9 Because of variation in the classification used, tumor stage and treatment results are often difficult to
Postoperative
split course radiotherapy
Table 2. Correlation
of squamous
cell carcinoma
of the oral tongue 0
of T-stage of primary tumor, local recurrence
No. of recurrences
No. of T2 patients
No. of T3 patients
No. of recurrences
M. BAMBERC et al
517
and radiation dose
No. of recurrences
No. of T4 patients
No. of recurrences
Ret.
No. of Tl patients
120@-1399 1400-1599 1600-1799 1800-1999 2000-2199
1 2 4 2 0
0 2 I 0 0
5 4 5 4 1
2 1 2 1 0
1 3 4 6 4
1 1 2 1 0
0 0 0 2 1
0 0 0 1 0
Total
9
3
19
6
18
5
3
1
compare.
In contrast
to the patient
collective
from
Chu’ and Fletcher3 and Delclos et ~l.,~ who employed the same staging method, the recurrence rate in Stage T1/7’2 of our collective was higher (Table 4). Both authors treated the smaller tumors initially with a combination of interstitial and external irradiation whereas our patients received intraoral cone- and teletherapy after surgery. This combined modality, however, could not achieve the contenting results of irradiation alone as in the early T-stages of the M. D. Anderson series.3,4 In smaller lesion interstitial therapy should be preferred: this allows the application of very large doses in a sharply defined region.’ During intraoral cone therapy, precision of application is diminished, particularly in elderly patients, by movement of the tongue. Following the pioneering efforts from Holthusen,14 Paterson17 and Strandqvist,” the interdependence of control rate and damage rate of surrounding tissue has been investigated by many authors. In order to achieve approximately 90% control in squamous cell
Stage
carcinoma of tonsillar fossa and supraglottical larynx tumors, Fletcher’ recommended 1800 ret for Tl lesions, 1900 ret for T2 and 2000 and more for T3 and T4 tumors. For the same type of tumors in Stage T2/T3 Shukovsky” considers 2000 ret necessary for a local control rate of 85%. Luk and Castroi reported similar results for T 1 carcinoma of the vocal cord. According to the experiences of Spanos et aLm 6000 rad tumor dose in 6 weeks (corresponding to 1758 ret) is necessary for local control of 90% of tongue tumors in Stage T 1, 7500 rad focal dose in 7.5 weeks (2033 ret) for control of more than 80% of T2/T3 tumors. Bedwinek et al.’ pointed out that with megavoltage treatment, focal doses greater than 7000 rad in 7 weeks lead to significantly increased rates of osteonecrosis in squamous cell carcinoma of the oral cavity. Depending
Table 3. Local recurrence
and ultimate failures after external
No. of patients
Recurrences salvaged by external irradiation
Tl T2 T3 T4
9 19 18 3
Total
49
No. of recurrences
upon
stage
and
previous
surgery,
Recurrences salvaged
irradiation
or surgery
Ultimate local failures No. of patients (%)
3
l/2
6t
5$ I
213 014 0
l/l l/l 0 111
l/9 319 5118 o/3
(11.1) (33.3) (27.7) (0)
15
319
313
9149
(18.4)
tGenera1 medical condition of two patients was not suitable for further therapy. SOne patient refused further therapy. Table 4. Local failures in correlation
Stage
Chu and Fletcher3 No. of patients
(%)
Tl T2 T3 T4
3152 17/100 27166 20130
(5.7) (17.0) (41 .O) (67.0)
Total
671248
(27.0)
our
tumor doses ranged from 5500 to 7ooO rad. In contrast to the cited authors,‘,9.‘5.‘9.20who usually irradiated with 1000 rad per week in a single series, our patients
Delclos et aP No. of patients
to T-stage of disease
(So)
Our results No. of patients
(%)
l/l8 6157 6127 0
(5.5) (10.5) (22.2) (0)
319 6119 S/l8 l/3
(33.3) (31.5) (27.7) (33.3)
13/102
(12.1)
15/49
(30.6)
518
Radiation Oncology 0 Biology 0 Physics
April 1979, Volume 5, Number 4
Fig. 3. The nominal standard dose (NSD)S modified by Gabriel-Jurgens et al.” and Gremmel et al.” NSD = Summary of the partial tolerances PTl and PT2 (if the tolerance limitation of the normal tissue is obtained in 2 series); tl = elapsed time in days of the first series; nl = number of fractions of the first series; RBE dl = dose per fraction of the first series; RBE(60Co) = RBE for beam used related to RBE for @‘Cobeam; R = gap time; t2 = elapsed time in days of the second series; n2 = number of fractions of the second series; d2 = dose per fraction of the second series; RBE = Relative biological effectiveness.
were treated by split course technique in 2 series with an interval of 2-3 weeks on the basis of previous reports.‘3~‘8 In order to obtain comparable values we converted our radiation parameters to nominal standard dose (NSD),6 using the formula given by Gabriel-Jiirgens et aI.” and Gremmel et al.” (Fig. 3). Thus, further considerations on the basis of the Ellis formula are related to the application of irregular fractionation modes and two series of radiation therapy. Thereafter it can be shown that our doses were in part substantially lower than those of other authors namely on the average 1640 ret for Tl tumors and 1730 ret for T2/T3 tumors. Million and Zimmermann16 reported a retrospective evaluation of continuous vs split course irradiation techniques in head and neck squamous cell carcinomas. In the advanced cases the results after split course therapy suggested poorer local control, but in these patients major complications could be decreased. The total dose was not increased for the split course group in contrast to the clinical experience of Holsti.13 With the exception of two ulcers in the primary tumor region, no radiation damages after split course were observed with the doses used in our clinic. However, it must be stated, that the low rate of side effects is linked with a higher recurrence rate in
smaller lesions. For the 21 patients with tumors of Stage T3 and T4 there is an overall recurrence rate of 28.5%. Only 15% local failures were seen in 13 patients who received in excess of 1800 ret. These remarkable results-more comparable to the cases of Chu and Fletcher3 and Delclos et al.4-were achieved in a small number of patients with advanced desease without increasing the radiation morbidity. In 89 patients with tumors of Stage Tl-T3, Delclos et ~1.~ noticed 21% soft tissue ulceration and 19% osteoradionecrosis. The local control in this split course series seems to be “dose dependent”, while the incidence of radiation damages can be diminished by split dose approach especially in advanced cases. According to these results and our experiences, we recommended a split course technique to deliver 1700 ret for T 1 tumors (3000 rad in 3 weeks followed by a 2 weeks respite and 3000 rad in 3 weeks again) for tumors in Stages T2 1800 and T3 1900 ret and 3000-3500 rads in 3-3.5 weeks again). Local recurrences were treated either by irradiation or surgery; in our patients it was apparent that the surgical treatment was more successful than irradiation. Whereas Hamberger et al.‘* reported poor prospects of success for both treatment modalities, our results were supported by the experiences and Lee* and Fletcher and Evers.’
of Cade
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