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Interstitial radiotherapy with Ir-192 as a palliative treatment modality in head and neck cancer
J. Cranio-Max.-Fac. Surg. i5 (1987) j. Cranio-Max.-Fac. Surg. 15 (1987) 365-368 © Georg Thieme Verlag Stuttgart • New York
Interstitial Radiotherapy with Ir-192 as a Palliative Treatment Modality in Head and Neck Cancer
365
Summary In selected patients with advanced head and neck cancer interstitial radiotherapy with Ir-192 can be used as a palliative treatment. Using two cases as examples, we report on our experiences with 19 patients.
Key-Words Head and neck tumours - Interstitial radiotherapy Ir-192, palliative treatment - Follow up
Alfred Paul Schmid 1, Kurt Vinzenz 2, Robert Pavelka 3, Hans Kdrcher 4, Werner Dobrowsky 1 1 Clinic for Radiotherapy and Radiobiology, Vienna University (Head: Prof. K.H. Kfircher, M.D.) 2 Clinic for Maxillo-Facial Surgery, Vienna University (Head: Prof. S. Wunderer, M.D., D.M.D.) 3 II. Clinic for Otorhinolaryngology, Vienna University (Head: Prof. K. Burian, M.D.) 4 Clinic for Dentistry, Graz University (Head: Prof. H. K61e, M.D., D.M.D.) Submitted 3.9. 1986; accepted 2 5 . 1 1 . 1986
Introduction The established methods for the treatment of head and neck tumours are surgery and radiotherapy. Chemotherapy - either local (intra-arterial) or systemic - can also be used. Frequently a combination of all these modalities is applied. With maxillofacial tumours, the selection of treatment strategies is a true challenge, because of the functional importance of this region, as well as the cosmetic and psychosocial problems which often accompany treatment. Optimal therapy and treatment outcome in this region are highly dependent on the TNM-staging. Though symptoms of maxillo-faxial tumours (persistent ulceration, non-aching swelling, etc.) may appear at a relatively early stage, the majority of patients first seek treatment when the disease is far advanced, so that curative therapy is frequently difficult and prognosis is generally unfavourable. In the early stages (T1-2, N0-1) primary radiotherapy, consisting of external beam megavoltage teletherapy (Cobalt-60, photons) and interstitial brachytherapy (Iridium-192), is successful (Pierquin et al., 1971). Radiation therapy is also used adjuvantly following primary definitive surgery. Generally with large or multiple lymph node metastases in the neck, surgical dissection followed by postoperative radiation is the treatment of choice. With initially unresectable tumours external beam radiotherapy can be used initially to reduce tumour size prior to surgery. Very large malignancies and recurrences are almost exclusively irradiated palliatively. We have combined external beam radiation and interstitial implants of Ir-192 as a palliative treatment for selected patients with advanced or recurrent head and neck tumours.
Indications for Palliative Ir-Implants Palliative measures are indicated in patients with either malignancies too large for surgical intervention or with relapses after surgical, radio- or chemotherapeutic treatment. Whereas in the curative stages (T1-2, N o - l ) it is feasi-
ble to outline a standard radiotherapy treatment regimen, in palliative cases therapy has to be adapted to the individual patient and his disease. From our point of view, there is an indication for palliative Ir-implants when a) patients with large primary tumours or relapses are in good general condition and b) the tumour is surgically unresectable or surgery is not accepted by the patient. k-implant therapy is usually combined with external beam teletherapy. In cases where previous radiation has been used - the external dose has to be kept low or even omitted. In large primary tumours, treatment is started with external beam megavoltage-teletherapy, and following tumour regression after 50 Gy (applied within 5 to 6 weeks) interstitial Ir-implants may be inserted. When there is no response, therapy should be stopped and another treatment modality should be considered.
Material and Methods From 1981-1983, 19patients with head and neck tumours underwent palliative interstitial Ir-therapy at the Clinic of Radiotherapy, Vienna University. Of these patients 6 had advanced tumours (stage IV according to AJC, T4N1M0 according to UICC), while 13 had recurrences after having undergone different prior therapy (surgery, radiotherapy, chemotherapy, combined modalites). Among the patients with recurrence 8 had already previously received radiotherapy with doses of 50 to 70Gy (1 to 4 years earlier), in one patient interstitial brachytherapy with Ir-192 had been applied for curative purposes. Histologically, there were 18 squamous cell malignancies and one recurrence after a malignant adenoma of the os ethmoidale. All patients (including those who had received radiotherapy previously) were irradiated with an external beam using 3 0 - 6 0 Gy (Co-60 or photons). Brachytherapy was given interstitially with Ir-192 (afterloading technique) at doses of 1 0 - 5 0 G y applied either in one single session or fractionated. Technical and physical details regarding Ir-192-implants by the afterloading technique have been described previously (Schmid et al., 1985). In order to illustrate individual and palliative procedures two case reports are presented, one of them dealing with a patient with an advanced stage IV primary tumour, the other with a tumour recurrent after treatment with a combination of surgery and chemotherapy.
Case 1 Male patient, 75 years old. Past medical history revealed he had had cerebral apoplexy (right) one year previously.
J. Cranio-Max.-Fac. Surg. 15 (1987)
366
A. P. Schmid et al.
treated with the same implant. The tongue malignancy received 30 Gy, while 17 Gy was given to the left side of the neck during a treatment period of 40 hours. Originally, an interstitial dose of at least 25 Gy was planned for the neck. However, the dose would have required a prolonged treatment time and the patient could not be expected to tolerate this due to his neurological problem. Two months after the therapy there was no clinical evidence of turnout in the tongue. There was a remission of lymph nodes with only a one centimetre fibrotic node remaining at the left angle of the jaw. Fourteen months after termination of therapy the patient died of a second cerebral apoplexy without evidence of tumour.
Fig. 1 Implantation site of Case 1. Five bow-shaped plastic tubes are implanted into the tongue tumour. In addition five metal tubes have been inserted in a linear fashion into lymph node metastases in left side of the neck, In a second step, radioactive Ir-192-wires will be afterloaded. The entire implantation unit will be removed after the full dose application,
Histologically, a squamous cell carcinoma of the tongue with metastases to lymph nodes of the neck had been verified. He had stage IV disease according to AJC and T3N3M0 according to UICC, respectively. Surgery was inappropriate due to age and past medical history, so the patient was admitted for radiotherapy. At the beginning of irradiation, the patient was in good general health and nutritional status was excellent. Treatment was started with 6 MeV photons given by a linear accelerator. A total external dose of 50 Gy (daily single doses of 2 Gy) was administered. As a radiation sensitizer, low-dosage Bleomycin was also used. Following turnout regression, an Ir-implantation was carried out 14 days after termination of teletherapy. Under general anaesthesia, inactive plastic tubes were implanted into the tongue in a special (bowshaped) geometric. arrangement and, at the same time, metallic tubes were implanted into the affected left side of the neck (Fig. 1). After recovery from anaesthesia the patient was transferred from the operating theatre to the irradiation room; radioactive Ir-192-wires of appropriate length and number were afterloaded. Because of the special geometric arrangement mentioned, both the tongue and left neck were
Table1
Local response to interstitial Ir-therapy
Results
Patients
n
CR
RE
PR
NR
PT RT
6 13
4 11
2 6
2 1
0 1
n CR RE PR NR PT RT
= = = = = = =
number of patients complete remission recurrence after primary complete remission partial remission no response primary tumours without pretreatment recurrences after pretreatment
Case 2 Male patient, 75 years old, diagnosis: carcinoma of the tongue crossing the midline, (stage IV). Initial primary treatment included preoperative local peritumoral immunotherapy with the immunomodulator OK-432-Picibanil, a Streptococcus pyogenes preparation (Chugai Comp., Japan). Subsequently, resection of 3/4 of the tongue, partial resection of the lower jaw, right neck dissection and left submandibular dissection were performed. Postoperatively, the patient was given adjuvant cytostatic chemotherapy following the Bitter regimen, with a total dose of 5 1 8 m g Oncovin, 588mg MTX, 150.4mg cisPlatinum. One year after surgery there was a recurrence, extending from the left cheek to the cranial base. A radical attempt to remove the tumour failed, due to tumour remaining at the junction of the A. carotis interna and the cranial base. Four weeks after surgery of the recurrent tumour Ir-therapy was initiated. For this purpose 5 metallic tubes were implanted via the right cheek into the remaining tumour and fixed externally to the skin (Figs. 2-5). After 2 days the patient was transferred to the irradiation room; radioactive Ir-192-wires - their lengths adjusted to the tumour location - were afterloaded into the metallic tubes. Within 2 weeks 50 Gy, given in 3 fractions, were applied (for dose distribution see Fig. 5). Additionally, 40 Gy were administered externally by means of a 6 MeV linear accelerator after a treatment interval of 14days. Subsequent examinations did not reveal any indication of the presence of the malignancy. The patient was without complaints or radiation reactions. One year after treatment, computed tomography showed a recurrence located partly intracranially partly in the occipital cranial base - i.e. outside the irradiation region. The patient was given chemotherapy (a so-called palliative Z-regimen) consisting of 500 mg Endoxan, 50 mg MTX and 50 mg 5-FU, but succumbed to his disease 14 days later.
The responses to combined radiotherapy are presented in Table 1. In the group of 6 patients with primary stage IV tumours without prior treatment, 4 local clinical total remissions were achieved, one patient died of local recurrence and one of generalized metastases. Two patients were tumour-free at the time of death, (one of them is referred to in Case 1). In 2 patients only local partial remissign was obtained (clinically, a tumour reduction > 50 %). Of the 13 patients with recurrences 11 had an initial total remission, 5 of them remaining alive, clinically tumourfree, for a mean observation time of 42 months. Six pa-
Interstitial Radiotherapy with Ir-192 as a Palliative Treatment Modality
Fi 8. 2 External part of implantation unit of Case 2. Five metal tubes are implanted in the preauricular region into the tumour by means of a template designed individually for the patient.
J. Cranio-Max.-Fac. Surg. 15 (1987)
367
Fig. 3 Control a,p. X-ray illustrating site of inactive metal tubes (Case 2).
"
~
MRXIMUM[O] =9999 1007.: 1000 150DOSEN[7.) 800 500 300 250 2~0 150 120 100 90 80 70 60 50 35 30 25 20
SCRLE = 1~.00 , 1.00 IMP. 10.0 9
Fig.4 Control X-ray illustrating site of tubes in the lateral view. Xray at 2 levels serves to calculate the dose distribution.
tients died of recurrent disease (in one of them, the recurrence appeared outside the irradiation area, see Case 2), or of sequential recurrence. Both external beam therapy and brachytherapy were well tolerated. Major complications (necrosis, fibrosis, ulcer) requiring surgery were not seen. All patients showed dose-dependent temporary erythema
Fig. 5
EBENE
Z = 1.0 CM
D o s e distribution of It-wires T h e first comprehensive iso-
dose is identical to the 100 Gy-isodose and was referred to for calculation of complete irradiation time.
of the skin, mucositis and xerostomia following external beam therapy. No late sequelae have been registered. Sumrfiing up the results obtained in both groups, it can be said: 5 patients are alive tumour-free (median observation period 42months), 2patients died tumour-free 8 and 14 months after therapy, respectively. Seven patients deve-
368
]. Cranio-Max.-Fac. Surg. 15 (1987)
loped subsequent recurrence (median relapse-free interval 12.5 months, with a minimum of 6 and a maximum of 19 months). In 3 patients, only a partial remission ( > 50 %) was achieved. One patient did not respond to therapy, another one died - though locally tumour-free - of a secondary blastoma 7 months after therapy. Apart from reversible radiation-induced reactions no side effects were noticed. Discussion and Conclusions There is no standard solution to the problem of optimal treatment for advanced head and neck tumours. This is due to two facts: first, the structures present in this region form a very complex, functional unit; second, prognosis of these tumours does not depend highly on distant metastases, but rather on local control of the primary tumour and on eventual lymphnode metastases. One of the crucial problems is the fact that in the majority of patients the malignant disease is already advanced at the time of diagnosis, reaching the limits of surgical therapy (Fries, 1975). For early stages there are relatively clear treatment schemes available, leading to comparably good results (70 to 90 % total remissions after an observation period of 2 to 5 years) - no matter whether they are obtained by surgery alone, by radiotherapy alone (external or interstitial irradiation, combined brachyteletherapy) or by a combination of surgical and radiotherapeutic modalities. In advanced tumours the prognosis becomes significantly less favourable. In tumour stages T3-4 and N1-3, survival times of 5 years are achieved in 20 to 30 % of cases (Wawro et al., 1970; Pierquin et al., 1971; Beahrs, 1972; Hamberger et al., 1976; Syed et al., 1977). For this reason, a considerable number of interdisciplinary clinical studies are under way, with the objective of improving prognosis (Ansfield et al., 1970; Gollin et al., 1972; Knowlton et al., 1975). Since in the majority of patients survival times are only 1.5 years from the time of diagnosis of recurrence (Fries, 1975), any progress in the field of recurrence therapy would be highly desirable. In advanced tumours or recurrent disease frequently palliative radiotherapy alone, in reduced doses, is administered. The aim in most cases is to reduce or eliminate pain or to reduce the turnout size in order to maintain vital functions (e.g. in the upper aerodigestive tract). There are reports stating that restoration to health by radiotherapy alone is impossible when the tumour has exceeded a certain critical limit (Kdrcher, 1983); yet it should be noted that - in individual cases - impressive results may be achieved by highdose irradiation and subsequent surgery (Kdrcher et al., 1985). If radical measures seem appropriate in individual cases (depending on factors such as age, general and nutritional condition) two treatment modalities are available: surgery and/or radiotherapy. Surgery alone can lead to severe functional and cosmetic defects, and greatly affect the psychological well-being of the patient. Equally, unfortunately, external beam radiotherapy alone may cause severe damage to normal tissue (fibrosis, necrosis). Interstitial radiotherapy with Ir-192 thus offers a true alternative. The afterloading procedure allows easy application of the radioactive It-wires as well as concentration of the dose in the target area, with only little radiation side effects on the
A. P. Schmid et al.: Interstitial Radiography with Ir-192 surrounding tissue due to the rapid decline of dose with distance from the sources. Thus, in combination with external high-dosage teletherapy, brachytherapy can he used tumoricidically. Whereas this method has already been established for small tumours of the oral cavity (Pierquin et al., 1971), we were able to demonstrate its efficiency in large-sized tumours, too (19 individual cases, retrospectively analyzed). We achieved primary clinical total remission in 15 patients. From our point of view, in patients receiving palliative therapy it is essential to develop individually-adapted treatment schedules, with special regard to both local tumour location and psychological problems of the patient. Close interdisciplinary cooperation as well as close contact between the clinics involved are required in order to outline the initial treatment strategy as well as to allow alterations of the strategy whenever necessary. In the cases reported here, Ir-implantation led to excellent palliative results, and in some cases also offered a chance of cure.
References Ansfield, F.J., G. Ramirez, H. L Davis: Treatment of advanced cancer of the head and neck. Cancer 25 (1970) 78 Beahrs, H. W.: In: American Cancer Society. Proceedings of the Nat. Cancer Conference, Lippincott (1972) 135 Fries, K: Karzinome der Mundh6hle und des Oberkiefers. In: Kiircher: Krebsbehandlung als interdisziplinfire Aufgabe. Springer, Berlin-Heidelberg-New York (1975) 294 Gollin, F. F., F. J. Ansfield, J. H. Brandenburg: Combined therapy in advanced head and neck cancer: A randomized study. AJR 114 (1972) 83 Hamberger, A.D., G.F. Fletcher, 0. M. Guillamondegui: Advanced squamous cell carcinoma of the oral cavity and oropharynx treated with irradiation and surgery. Radiology 119 (1976) 433 Kdrcher, H., H. Eskid, A. P. Schmid: Neue kombinierte radiologischchirurgische Therapiem6glichkeiten bei inoperablen Geschwiilsten des Oberkiefers. Dtsch. Zschr. Mund-Kiefer-Geschichtschir. 9 (1985) 26 Kdrcher, K.H.: Radiotherapeutische Onkologie. Klinische Falldemonstrationen. Maudrich. Wien-Miinchen-Bern (1983) 43 Knowlton, A.H., B. Percarpio, S. Bobrow: Methotrexate and radiation therapy in the treatment of advanced head and neck tumors. Radiology 116 (1975) 709 Pierquin B., D.J. Chassagne, F. Baillet, J.R. Castro: The place of implantation in tongue and floor of mouth cancer. JAMA 215 (1971) 961 Schmid, A.P., R.Hawliczek, H.Kdrcher, K.K. Yinzenz, O.Schlappack, W. Seitz: Die interstitielle Strahlentherapie maxillofazialer Tumoren mit Ir-192 and Jod-125. Dtsch. Zschr. Mund-KieferGeschichtschir. 9 (1985) 77 Syed, A. M. N., B. H. Feder, F. W. George III: Persistent carcinoma of the oropharynx and oral cavity retreated by afterloading interstitial Iridium-192 implant. Cancer 39 (1977) 2443 Wawro, N. N., A. Babcock, L. E[lison: Cancer of the tongue. Experience at the Hartford Hospital from 1931 to 1963. Am. J. Surg. 110 (1970) 455
A.P. Schmid, M.D. Clinic for Radiotherapy Allgemeines Krankenhaus Al~er Stra[3e 4 A-1090 Vienna Austria
Interstitial Radiotherapy with Ir-192 as a Palliative Treatment Modality in Head and Neck Cancer
365
Summary In selected patients with advanced head and neck cancer interstitial radiotherapy with Ir-192 can be used as a palliative treatment. Using two cases as examples, we report on our experiences with 19 patients.
Key-Words Head and neck tumours - Interstitial radiotherapy Ir-192, palliative treatment - Follow up
Alfred Paul Schmid 1, Kurt Vinzenz 2, Robert Pavelka 3, Hans Kdrcher 4, Werner Dobrowsky 1 1 Clinic for Radiotherapy and Radiobiology, Vienna University (Head: Prof. K.H. Kfircher, M.D.) 2 Clinic for Maxillo-Facial Surgery, Vienna University (Head: Prof. S. Wunderer, M.D., D.M.D.) 3 II. Clinic for Otorhinolaryngology, Vienna University (Head: Prof. K. Burian, M.D.) 4 Clinic for Dentistry, Graz University (Head: Prof. H. K61e, M.D., D.M.D.) Submitted 3.9. 1986; accepted 2 5 . 1 1 . 1986
Introduction The established methods for the treatment of head and neck tumours are surgery and radiotherapy. Chemotherapy - either local (intra-arterial) or systemic - can also be used. Frequently a combination of all these modalities is applied. With maxillofacial tumours, the selection of treatment strategies is a true challenge, because of the functional importance of this region, as well as the cosmetic and psychosocial problems which often accompany treatment. Optimal therapy and treatment outcome in this region are highly dependent on the TNM-staging. Though symptoms of maxillo-faxial tumours (persistent ulceration, non-aching swelling, etc.) may appear at a relatively early stage, the majority of patients first seek treatment when the disease is far advanced, so that curative therapy is frequently difficult and prognosis is generally unfavourable. In the early stages (T1-2, N0-1) primary radiotherapy, consisting of external beam megavoltage teletherapy (Cobalt-60, photons) and interstitial brachytherapy (Iridium-192), is successful (Pierquin et al., 1971). Radiation therapy is also used adjuvantly following primary definitive surgery. Generally with large or multiple lymph node metastases in the neck, surgical dissection followed by postoperative radiation is the treatment of choice. With initially unresectable tumours external beam radiotherapy can be used initially to reduce tumour size prior to surgery. Very large malignancies and recurrences are almost exclusively irradiated palliatively. We have combined external beam radiation and interstitial implants of Ir-192 as a palliative treatment for selected patients with advanced or recurrent head and neck tumours.
Indications for Palliative Ir-Implants Palliative measures are indicated in patients with either malignancies too large for surgical intervention or with relapses after surgical, radio- or chemotherapeutic treatment. Whereas in the curative stages (T1-2, N o - l ) it is feasi-
ble to outline a standard radiotherapy treatment regimen, in palliative cases therapy has to be adapted to the individual patient and his disease. From our point of view, there is an indication for palliative Ir-implants when a) patients with large primary tumours or relapses are in good general condition and b) the tumour is surgically unresectable or surgery is not accepted by the patient. k-implant therapy is usually combined with external beam teletherapy. In cases where previous radiation has been used - the external dose has to be kept low or even omitted. In large primary tumours, treatment is started with external beam megavoltage-teletherapy, and following tumour regression after 50 Gy (applied within 5 to 6 weeks) interstitial Ir-implants may be inserted. When there is no response, therapy should be stopped and another treatment modality should be considered.
Material and Methods From 1981-1983, 19patients with head and neck tumours underwent palliative interstitial Ir-therapy at the Clinic of Radiotherapy, Vienna University. Of these patients 6 had advanced tumours (stage IV according to AJC, T4N1M0 according to UICC), while 13 had recurrences after having undergone different prior therapy (surgery, radiotherapy, chemotherapy, combined modalites). Among the patients with recurrence 8 had already previously received radiotherapy with doses of 50 to 70Gy (1 to 4 years earlier), in one patient interstitial brachytherapy with Ir-192 had been applied for curative purposes. Histologically, there were 18 squamous cell malignancies and one recurrence after a malignant adenoma of the os ethmoidale. All patients (including those who had received radiotherapy previously) were irradiated with an external beam using 3 0 - 6 0 Gy (Co-60 or photons). Brachytherapy was given interstitially with Ir-192 (afterloading technique) at doses of 1 0 - 5 0 G y applied either in one single session or fractionated. Technical and physical details regarding Ir-192-implants by the afterloading technique have been described previously (Schmid et al., 1985). In order to illustrate individual and palliative procedures two case reports are presented, one of them dealing with a patient with an advanced stage IV primary tumour, the other with a tumour recurrent after treatment with a combination of surgery and chemotherapy.
Case 1 Male patient, 75 years old. Past medical history revealed he had had cerebral apoplexy (right) one year previously.
J. Cranio-Max.-Fac. Surg. 15 (1987)
366
A. P. Schmid et al.
treated with the same implant. The tongue malignancy received 30 Gy, while 17 Gy was given to the left side of the neck during a treatment period of 40 hours. Originally, an interstitial dose of at least 25 Gy was planned for the neck. However, the dose would have required a prolonged treatment time and the patient could not be expected to tolerate this due to his neurological problem. Two months after the therapy there was no clinical evidence of turnout in the tongue. There was a remission of lymph nodes with only a one centimetre fibrotic node remaining at the left angle of the jaw. Fourteen months after termination of therapy the patient died of a second cerebral apoplexy without evidence of tumour.
Fig. 1 Implantation site of Case 1. Five bow-shaped plastic tubes are implanted into the tongue tumour. In addition five metal tubes have been inserted in a linear fashion into lymph node metastases in left side of the neck, In a second step, radioactive Ir-192-wires will be afterloaded. The entire implantation unit will be removed after the full dose application,
Histologically, a squamous cell carcinoma of the tongue with metastases to lymph nodes of the neck had been verified. He had stage IV disease according to AJC and T3N3M0 according to UICC, respectively. Surgery was inappropriate due to age and past medical history, so the patient was admitted for radiotherapy. At the beginning of irradiation, the patient was in good general health and nutritional status was excellent. Treatment was started with 6 MeV photons given by a linear accelerator. A total external dose of 50 Gy (daily single doses of 2 Gy) was administered. As a radiation sensitizer, low-dosage Bleomycin was also used. Following turnout regression, an Ir-implantation was carried out 14 days after termination of teletherapy. Under general anaesthesia, inactive plastic tubes were implanted into the tongue in a special (bowshaped) geometric. arrangement and, at the same time, metallic tubes were implanted into the affected left side of the neck (Fig. 1). After recovery from anaesthesia the patient was transferred from the operating theatre to the irradiation room; radioactive Ir-192-wires of appropriate length and number were afterloaded. Because of the special geometric arrangement mentioned, both the tongue and left neck were
Table1
Local response to interstitial Ir-therapy
Results
Patients
n
CR
RE
PR
NR
PT RT
6 13
4 11
2 6
2 1
0 1
n CR RE PR NR PT RT
= = = = = = =
number of patients complete remission recurrence after primary complete remission partial remission no response primary tumours without pretreatment recurrences after pretreatment
Case 2 Male patient, 75 years old, diagnosis: carcinoma of the tongue crossing the midline, (stage IV). Initial primary treatment included preoperative local peritumoral immunotherapy with the immunomodulator OK-432-Picibanil, a Streptococcus pyogenes preparation (Chugai Comp., Japan). Subsequently, resection of 3/4 of the tongue, partial resection of the lower jaw, right neck dissection and left submandibular dissection were performed. Postoperatively, the patient was given adjuvant cytostatic chemotherapy following the Bitter regimen, with a total dose of 5 1 8 m g Oncovin, 588mg MTX, 150.4mg cisPlatinum. One year after surgery there was a recurrence, extending from the left cheek to the cranial base. A radical attempt to remove the tumour failed, due to tumour remaining at the junction of the A. carotis interna and the cranial base. Four weeks after surgery of the recurrent tumour Ir-therapy was initiated. For this purpose 5 metallic tubes were implanted via the right cheek into the remaining tumour and fixed externally to the skin (Figs. 2-5). After 2 days the patient was transferred to the irradiation room; radioactive Ir-192-wires - their lengths adjusted to the tumour location - were afterloaded into the metallic tubes. Within 2 weeks 50 Gy, given in 3 fractions, were applied (for dose distribution see Fig. 5). Additionally, 40 Gy were administered externally by means of a 6 MeV linear accelerator after a treatment interval of 14days. Subsequent examinations did not reveal any indication of the presence of the malignancy. The patient was without complaints or radiation reactions. One year after treatment, computed tomography showed a recurrence located partly intracranially partly in the occipital cranial base - i.e. outside the irradiation region. The patient was given chemotherapy (a so-called palliative Z-regimen) consisting of 500 mg Endoxan, 50 mg MTX and 50 mg 5-FU, but succumbed to his disease 14 days later.
The responses to combined radiotherapy are presented in Table 1. In the group of 6 patients with primary stage IV tumours without prior treatment, 4 local clinical total remissions were achieved, one patient died of local recurrence and one of generalized metastases. Two patients were tumour-free at the time of death, (one of them is referred to in Case 1). In 2 patients only local partial remissign was obtained (clinically, a tumour reduction > 50 %). Of the 13 patients with recurrences 11 had an initial total remission, 5 of them remaining alive, clinically tumourfree, for a mean observation time of 42 months. Six pa-
Interstitial Radiotherapy with Ir-192 as a Palliative Treatment Modality
Fi 8. 2 External part of implantation unit of Case 2. Five metal tubes are implanted in the preauricular region into the tumour by means of a template designed individually for the patient.
J. Cranio-Max.-Fac. Surg. 15 (1987)
367
Fig. 3 Control a,p. X-ray illustrating site of inactive metal tubes (Case 2).
"
~
MRXIMUM[O] =9999 1007.: 1000 150DOSEN[7.) 800 500 300 250 2~0 150 120 100 90 80 70 60 50 35 30 25 20
SCRLE = 1~.00 , 1.00 IMP. 10.0 9
Fig.4 Control X-ray illustrating site of tubes in the lateral view. Xray at 2 levels serves to calculate the dose distribution.
tients died of recurrent disease (in one of them, the recurrence appeared outside the irradiation area, see Case 2), or of sequential recurrence. Both external beam therapy and brachytherapy were well tolerated. Major complications (necrosis, fibrosis, ulcer) requiring surgery were not seen. All patients showed dose-dependent temporary erythema
Fig. 5
EBENE
Z = 1.0 CM
D o s e distribution of It-wires T h e first comprehensive iso-
dose is identical to the 100 Gy-isodose and was referred to for calculation of complete irradiation time.
of the skin, mucositis and xerostomia following external beam therapy. No late sequelae have been registered. Sumrfiing up the results obtained in both groups, it can be said: 5 patients are alive tumour-free (median observation period 42months), 2patients died tumour-free 8 and 14 months after therapy, respectively. Seven patients deve-
368
]. Cranio-Max.-Fac. Surg. 15 (1987)
loped subsequent recurrence (median relapse-free interval 12.5 months, with a minimum of 6 and a maximum of 19 months). In 3 patients, only a partial remission ( > 50 %) was achieved. One patient did not respond to therapy, another one died - though locally tumour-free - of a secondary blastoma 7 months after therapy. Apart from reversible radiation-induced reactions no side effects were noticed. Discussion and Conclusions There is no standard solution to the problem of optimal treatment for advanced head and neck tumours. This is due to two facts: first, the structures present in this region form a very complex, functional unit; second, prognosis of these tumours does not depend highly on distant metastases, but rather on local control of the primary tumour and on eventual lymphnode metastases. One of the crucial problems is the fact that in the majority of patients the malignant disease is already advanced at the time of diagnosis, reaching the limits of surgical therapy (Fries, 1975). For early stages there are relatively clear treatment schemes available, leading to comparably good results (70 to 90 % total remissions after an observation period of 2 to 5 years) - no matter whether they are obtained by surgery alone, by radiotherapy alone (external or interstitial irradiation, combined brachyteletherapy) or by a combination of surgical and radiotherapeutic modalities. In advanced tumours the prognosis becomes significantly less favourable. In tumour stages T3-4 and N1-3, survival times of 5 years are achieved in 20 to 30 % of cases (Wawro et al., 1970; Pierquin et al., 1971; Beahrs, 1972; Hamberger et al., 1976; Syed et al., 1977). For this reason, a considerable number of interdisciplinary clinical studies are under way, with the objective of improving prognosis (Ansfield et al., 1970; Gollin et al., 1972; Knowlton et al., 1975). Since in the majority of patients survival times are only 1.5 years from the time of diagnosis of recurrence (Fries, 1975), any progress in the field of recurrence therapy would be highly desirable. In advanced tumours or recurrent disease frequently palliative radiotherapy alone, in reduced doses, is administered. The aim in most cases is to reduce or eliminate pain or to reduce the turnout size in order to maintain vital functions (e.g. in the upper aerodigestive tract). There are reports stating that restoration to health by radiotherapy alone is impossible when the tumour has exceeded a certain critical limit (Kdrcher, 1983); yet it should be noted that - in individual cases - impressive results may be achieved by highdose irradiation and subsequent surgery (Kdrcher et al., 1985). If radical measures seem appropriate in individual cases (depending on factors such as age, general and nutritional condition) two treatment modalities are available: surgery and/or radiotherapy. Surgery alone can lead to severe functional and cosmetic defects, and greatly affect the psychological well-being of the patient. Equally, unfortunately, external beam radiotherapy alone may cause severe damage to normal tissue (fibrosis, necrosis). Interstitial radiotherapy with Ir-192 thus offers a true alternative. The afterloading procedure allows easy application of the radioactive It-wires as well as concentration of the dose in the target area, with only little radiation side effects on the
A. P. Schmid et al.: Interstitial Radiography with Ir-192 surrounding tissue due to the rapid decline of dose with distance from the sources. Thus, in combination with external high-dosage teletherapy, brachytherapy can he used tumoricidically. Whereas this method has already been established for small tumours of the oral cavity (Pierquin et al., 1971), we were able to demonstrate its efficiency in large-sized tumours, too (19 individual cases, retrospectively analyzed). We achieved primary clinical total remission in 15 patients. From our point of view, in patients receiving palliative therapy it is essential to develop individually-adapted treatment schedules, with special regard to both local tumour location and psychological problems of the patient. Close interdisciplinary cooperation as well as close contact between the clinics involved are required in order to outline the initial treatment strategy as well as to allow alterations of the strategy whenever necessary. In the cases reported here, Ir-implantation led to excellent palliative results, and in some cases also offered a chance of cure.
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A.P. Schmid, M.D. Clinic for Radiotherapy Allgemeines Krankenhaus Al~er Stra[3e 4 A-1090 Vienna Austria