88
J. Cranio-Max.-Fac. Surg. 18 (1990)
J. Cranio-Max.-Fac.Surg. 18 (1990) 88-90 © GeorgThiemeVerlagStuttgart • New York
Regional Chemotherapy of Inoperable Maxillofacial Tumours Combined with Radiotherapy Long Term Results Karl HoIlrnann 1, Georg Mailath 1, Michael Rasse 1, Joseph Kiihlh6ck 2, Brigitte Stadler 3 1Dept. of Oral and Maxillo-FacialSurgery 2(Head:Prof.Dr. Ewers,M. D., D.M. D.),Universityof Vienna IL MedicalDept. (Head:Prof. G. Geyer,M.D.), Universityof Vienna 3Dept. of Radiotherapyand Radiobiology (Head:Prof. K.-H. K~ircher,M.D.),Universityof Vienna,Austria
Summary At the Department of Oral Maxillo-Facial Surgery, University of Vienna, we have from January 1973 to September 1985, subjected 117 patients with inoperable malignant tumours in the maxillo-facial area to intra-arterial chemotherapy consisting of methotrexate and bleomycin. In this group 103 patients have also been given radiotherapy. In this report only 68 patients of the group of 103 patients who have undergone combined treatment have been considered eligible for evaluation on the basis of their post-therapeutic survival time, which ranged from 2 to 11 years. 10 cases with complete remission and 34 cases with partial remission were observed, indicating that 65 % responded to combined treatment. Key words Chemotherapy - Intra-arterial cytostatic therapy Radiation of maxillo-facial tumours - Remission rates
Submitted 29.3. 1988; accepted 5.7. 1989
Introduction
Methods and Materials
Drug therapy of solid malignant tumours in the maxillofacial area has until the present, had limited indications, compared to surgical and radiological treatment. Bleomycin as well as methotrexate have proven to be potent cytostatic agents. Bitter (1973)pointed out the efficacy of these drugs when administered in combination. Sakamoto and Sakha (1974) discovered the efficacy of bleomycin in combination with radiotherapy in animal studies. After, or along with, surgical intervention and/or radiotherapy, intravenous mono or combination regimens applied in addition have led to remission rates of 33 to 84 % (Bagshaw et al., 1967; Richard et al., 1974; Berdal, 1976 and Carter, 1977). Yet the duration of remission obtained lasted only for weeks or months. With the purpose of increasing the concentration of cytotoxic substances locally, while simultaneously reducing systemic side effects, intraarterial studies have been carried out since 1958. Many reports give evidence of this (KapIan et al., 1966; Bitter, 1977; Arcangeli et al., 1983 and Hollmann et al., 1983). Yet, to date, it is not proven that intra-arterial administration of cytostatic agents has any therapeutic advantage over intra-venous systemic therapy (Bier et al., 1979). At the Department of Oral and Maxillo-facial Surgery, University of Vienna, it is presently still common practice to consider primary carcinoma to be a clear case for surgical intervention. Recent improvement in reconstructive measures greatly favours surgical intervention. Only when tumours have already destroyed the base of the skull or the muscular apparatus of the spine or when the inlet of the thorax has been reached, do we frequently refrain from surgical intervention. In these cases since 1973 we have consistently applied combination therapy, by introducing bleomycin and methotrexate into the tumour-supplying artery, combined with radiotherapy. The purpose of this study was to present results with respect to remission rates and long-term survival.
At the Department of Oral and Maxillo-Facial Surgery, University of Vienna, since 1973, patients have been treated with constant regimens: Methotrexate or bleomycin are administered by means of an intra-arterial catheter which is inserted either retrograde via the superficial temporal artery, the superior thyroid artery or orthograde into the external carotid artery. After the catheter position has been determined angiographically, a daily morning dose of 25 mg methotrexate and 15 mg bleomycin in the evening are infused with a motor driven pump. Infusion duration is 2 hours in both cases. As an antidote to methotrexate, the patient receives an intramuscular dose of 3 mg calcium leucovorin 4 times a day. The daily methotrexate dose is followed by radiation therapy 5 times per week, each dose consisting of 2 Gy. Basically at least 300 mg bleomycin, 5 0 0 m g methotrexate should be administered within 3 weeks and 60 Gy within 6 weeks. The remission rate was assessed 1 month after finishing the therapy. 19 patients had already died before this first assessment of turnout remission. 16 more of the 103 patients could not be included in the study because less than 4 years had elapsed since the end of therapy. So this study only concerns patients treated between 1973 and 1984 (the mean age was 57.5 y; min. 40, max. 75; 80 % within 5 0 - 7 0 years). Among the 68 there were 34 cases of tumour recurrence, which had been pretreated cytostatically, by radiation or surgery. In the paper of Szepesi et al. 1985, and Hollmann et al. 1981 there was no evidence of any statistically significant difference in life expectancy between patients with and those without pretreatment. So we did not a priori separate these two groups. The difficulty in quantifying remission of solid tumours especially in the maxillo-facial area necessitated strict adherence to the following criteria for evaluation purposes. Only in such cases where tumours were not identifiable by clinical means, hence not requiring further therapy, were
Regional Chemotherapy of Inoperable Maxillofacial Tumours
J. Cranio-Max.-Fac. Surg. i8 (1990)
89
Results •- - a - - •
I00
80
•
---o---
CR OVERALL PR NC TG:B no ev.d. TG:B ev.d.
60. 40'
:i
!
2'0
0
!
40
6'0
do
,00
MONTHS
Fig. 1
~ 100
~
Ii 80
\
--,,--
~
~
•
CR OVERALL
PR TG:B no ev.d, In
60 g
40 20
In 36 cases the tumours had already reached a T4NoM0-stage, at the onset of therapy and in 32 cases a T4N1-3M0-stage. With all patients the diagnosis was confirmed histologically. All patients had squamous cell carcinomas of varying degrees of keratinisation. Primary cancer was localized in the maxillary area in 22 patients, 18 patients were affected in the tonsillar region and 16 patients in the area of the tongue and the floor of the mouth. In 10 patients the tumour was located in the lower jaw, in one case in the lips and in another in the cheeks. The average dose of bleomycin administered was 302 mg (max. 495 rag, rain. 125 mg) and the average methotrexate dose was 4 9 4 m g (max. 1072mg, min. 50mg). 57 of 68 patients received the desired therapy dose of 500 mg methotrexate and 300 mg bleomycin and even above this quantity. Also 57 of 68 received 60 Gy of radiotherapy. In 11 cases a mean dose of 30 Gy only could be administered because of prior radiation therapy. 10 cases with complete remission and 34 cases with partial remission were observed, indicating that 65 % responded to combined treatment. On average, complete remission lasted for 48 months (max. 122 months, min. 3 months) and partial remission only for 5 months (max. 10 months, rain. 1 month). The difference in average remission duration is statistically significant (p = 0.0003). Similarly, the difference between median survival time for complete remission (median ST 50months) and partial remission (median ST 14 months) is significant ( p = 0.001). The life table procedure of Kaplan and Meier served to prognosticate a survival time of 1 year for 50 % of the patients, 2 years for 27 %, 3 years for 19 % 4 years for 12 % and 5 years for 10 % (Figs. 1 and 2). Discussion and Conclusions
0
0
i
I
20
40
I
I
I
60
80
100
MONTHS
Fig.2 Fig.l,
2 Life table c o m p a r i s o n of inoperable maxillo-facial malignant tumours, patients (n = 68). CR = complete remission, PR = partial remission, NC = no change•
they considered to be in a state of complete remission (CR). Tumours which showed readily indentifiable regression were considered to be partially remitted (PR). Other cases were termed "no change" (NC). Post therapeutic survical time served as the basis for evaluation of the success of treatment. Statistics
For life table comparison, the Breslow- as well as the Mantel-Cox tests were applied, p ( 0.05 was taken as a significance level.
The application of methotrexate and bleomycin for treatment of malignant tumours in the maxillo-facial area has often been described (Richard et al., 1974; Bilder and Igornova, 1974; Bitter, 1974, and Hollmann et al., 1979). We do not share the view that intra-arterial cytostatic therapy has no measurable advantage over systemic intravenous therapy. We are convinced that local perfusion of cytostatic agents produces a dose increase in the turnout area, whilst action on the periphery is simultaneously reduced; in spite of local side effects of intra-arterial therapy such as ipsilateral mucositis and ipsilateral alopecia. In those 68 patients included in this study, side effects were in no way potentially fatal and were always reversible and moderate. It is widely accepted that this type of cytostatic therapy constitutes a potential danger because methotrexate may cause marrow depression, and pulmonary fibrosis could be caused by bleomycin. The doses applied have never led to fatal bone marrow depression. In 4 instances therapy was discontinued because of thrombocytopoenia and in 2 instances, leucopoenia. Statistical reviews show that pulmonary fibrosis develops in 3 % of all cases when methotrexate is administered in such quantities. In our study not a single case of pulmonary fibrosis was reported.
90
J. Cranio-Max.-Fac. Surg. 18 (1990)
K. Hollmann et al.:Regional Chemotherapy of Inoperable Maxillofacial Tumours
Unilateral mucositis was reported after an average of 17 days in 56 cases and because food intake caused severe pain, alimentation was provided by means of tube feeding in a few cases. A more or less severe unilateral, but completely reversible alopecia was reported in almost all cases. Within an observation period of 5 to 11 years permanent cure was reported in 6 out of 68 patients. Twelve patients survived for at least 2 years after the commencement of therapy. In all, a complete remission was observed in 10 cases, i. e. almost one sixth and in at least half of all cases partial remission could be achieved. The figures show the extent to which survival is influenced in relation to the type of remission. 50 V0 of patients with complete remission still survived after 5 years c o m p a r e d to 3 % with partial remission w h o did not even survive for up to 4 years. N o t a single patient with a progressive or a persistent t u m o u r survived for up to 3 years. An interpretation of these results stresses the importance of achieving complete remission to give a better prognosis. The survival time of patients with partial remission and persistent tumours showed no statistically significant difference. To compare the results with the prognostic index of the DOSAK study (Platz et al., 1982) see life table comparison 1 and 2. Patients of the DOSAK study treatment group B (patients w i t h o u t radical surgical treatment and with alternative therapies) are listed in Table I as TG:B no ev. d., if there was no evidence of disease, TG:B ev. d., if there was evidence of disease after treatment and if lymphnodes were not palpable or clinically negative or clinically positive but movable. In Table 2 we show patients in this study with clinically positive, fixed lymphnodes with and without evidence of disease (TG:B no ev. d., In; TG:B ev. d., In). Table 1 demonstrates a better prognosis for patients with complete remission than for patients with no evidence of disease in the DOSAK t r e a t m e n t group B and a better prognosis for patients with partial remission than for patients of t r e a t m e n t group B with evidence of disease. This is even more obvious in Table 2 where the estimated survival rates of the DOSAK patients with positive fixed lymphnodes are displayed. Since we do not k n o w the patient data to c o m p a r e with our own we cannot check statistical significance in these differences.
Berdal, P.: Gann monograph on cancer research, No. 19. Fundamental and clinical studies of bleomycin. University of Tokyo Press 1976 Bier, J., P. Bender, K. Bitter: CO-bleomycin kinetics in normal and turnout-bearing mice after local and systemic administration. J. Max.-Fac. Surg. 7 (1979) 32 Bilder, J., J. Hornova: Synchronized combination of bleomycin and methotrexate in regional chemotherapy of orofacial carcinomas. Neoplasma 21 (1974) 14 Bitter, K.: Erste Ergebnisse der zytostatischen Behandlung von Plattenepithelcarcinomen in der Mundh6hle mit einer Kombination von Methotrexat und Bleomycin. Dtsch. Zahn-, Mund- und Kieferheilk. 60 (1973) 2 Bitter, K.: Immunity suppression by bleomycin and methotrexate combined treatment in patients with epidermoid carcinomas of the oral cavity. J. Max.-Fac. Surg. 2 (1974) 35 Bitter, K.: Bleomycin-methotrexate-chemotherapy in combination with telecobalt-radiation for patients suffering from advanced oral carcinoma. J. Max.-Fac. Surg. 5 (1977) 75 Carter, S. K.: The chemotherapy of head and neck cancer. Semin. Onkol. 4 (1977) 413 Hollmann, K., G. Mailath, J. Kiihbfck, W. Seitz: Combined intraarterial chemotherapy of methotrexate, bleomycin and radiation for advanced inoperable tumors of the head and neck region. 13th International Congress of Chemotherapy, Vienna, 1983. Kongret~band SE 12.1.11-5 Hollmann, K., W. Jesch, J. Kiihlb6ck, J. Dimopoulus: Combined intraarterial chemotherapy and radiation therapy of turnouts in the maxillofacial region. J. Max.-Fac. Surg. 7 (1979) 191 Hollmann, K., G. Mailath, J. Kiihb6ck, W. Seitz: Die Kombinationsbehandlung orofacialer Malignome mit Strahlen und Zytostatika. Z. Stomatol. (1981) 171-177 KapIan, H. S., ILL. S. Doggett, M. A. Bagshaw, T. S. Nelsen: Radiotherapy of advanced head and neck cancer combined with intraarterial infusion of chemotherapeutic or radiosensitizing agents. In: Proceedings of the international conference on radiation biology and cancer radiation. Society of Japan, Kyoto, Japan (1966) 193 Platz, H., R. Fries, M. Hudec: Therapieabhfingiger Prognoseindex TPI. D6sak, Lienz-Wien 1982 Richard, J. M., H. Sancho, Y. Lepintre, J. Radory, B. Pierquin: Intraarterial chemotherapy and telecobalt therapy in cancer of the oral cavity and oropharynx. Cancer 34 (1974) 491 Sakamoto, K., M. Sakha: The effect of Neomycin and its effects combined with radiation on murine squamous carcinoma in vivo. Brit. J. Cancer 30 (1974) 463
References
Arcangeli, G., C. Nervi, R. Righini, G. Creaton, M. A. Mirri, A. Guerra: Combined radiation and drugs: The effect of intraarterial chemotherapy followed by radiotherapy in head and neck cancer. Radiother. Oncol. 1 (1983) 101 Bagshaw, M. A., R. L S. Doggett, K. C. Smith, H. S. Kaplan, T. S. Nelsen" Intraarterial, 5-bromodeoxy-uridine and X-ray therapy. Amer. J. Roentgenol. 99 (1967) 886
Prof. K. Hollmann, M. D., D.M.D. Dept. of Oral and Maxillo-FacialSurgery University Hospital of Vienna Alserstrafle 4 A-I090 Wien Austria
Book Reviews
McGowan, D. A. (Ed.): An Atlas of Minor Oral Surgery. Principles and Practice. 1989. 132 pp. Martin Dunitz Ltd., London. £ 30.This book is aimed principally at dental practitioners and undergraduate dental students. It begins with some general principles of minor oral surgery such as diagnosis and treatment planning, preoperative preparation, the operation and postoperative care, and continues as a step-by-step atlas of the commoner minor oral surgical procedures. Each procedure is illustrated by high quality colour photographs. There is minimal written material making each section
easy to follow. - Unfortunately, some procedures lack important details necessary for the inexperienced practitioner, or student, such as the technique of sectioning impacted third molars, checking for perforations into the maxillary sinus after removal of upper molar and premolar teeth, and orthograde apicectomy as performed in many countries. - Nevertheless, as mentioned in its preface, this book is a good guide to all those who wish to learn, or improve their knowledge of this branch of the surgeons art. R.A.C.A.V.
J. Cranio-Max.-Fac. Surg. 18 (1990)
J. Cranio-Max.-Fac.Surg. 18 (1990) 88-90 © GeorgThiemeVerlagStuttgart • New York
Regional Chemotherapy of Inoperable Maxillofacial Tumours Combined with Radiotherapy Long Term Results Karl HoIlrnann 1, Georg Mailath 1, Michael Rasse 1, Joseph Kiihlh6ck 2, Brigitte Stadler 3 1Dept. of Oral and Maxillo-FacialSurgery 2(Head:Prof.Dr. Ewers,M. D., D.M. D.),Universityof Vienna IL MedicalDept. (Head:Prof. G. Geyer,M.D.), Universityof Vienna 3Dept. of Radiotherapyand Radiobiology (Head:Prof. K.-H. K~ircher,M.D.),Universityof Vienna,Austria
Summary At the Department of Oral Maxillo-Facial Surgery, University of Vienna, we have from January 1973 to September 1985, subjected 117 patients with inoperable malignant tumours in the maxillo-facial area to intra-arterial chemotherapy consisting of methotrexate and bleomycin. In this group 103 patients have also been given radiotherapy. In this report only 68 patients of the group of 103 patients who have undergone combined treatment have been considered eligible for evaluation on the basis of their post-therapeutic survival time, which ranged from 2 to 11 years. 10 cases with complete remission and 34 cases with partial remission were observed, indicating that 65 % responded to combined treatment. Key words Chemotherapy - Intra-arterial cytostatic therapy Radiation of maxillo-facial tumours - Remission rates
Submitted 29.3. 1988; accepted 5.7. 1989
Introduction
Methods and Materials
Drug therapy of solid malignant tumours in the maxillofacial area has until the present, had limited indications, compared to surgical and radiological treatment. Bleomycin as well as methotrexate have proven to be potent cytostatic agents. Bitter (1973)pointed out the efficacy of these drugs when administered in combination. Sakamoto and Sakha (1974) discovered the efficacy of bleomycin in combination with radiotherapy in animal studies. After, or along with, surgical intervention and/or radiotherapy, intravenous mono or combination regimens applied in addition have led to remission rates of 33 to 84 % (Bagshaw et al., 1967; Richard et al., 1974; Berdal, 1976 and Carter, 1977). Yet the duration of remission obtained lasted only for weeks or months. With the purpose of increasing the concentration of cytotoxic substances locally, while simultaneously reducing systemic side effects, intraarterial studies have been carried out since 1958. Many reports give evidence of this (KapIan et al., 1966; Bitter, 1977; Arcangeli et al., 1983 and Hollmann et al., 1983). Yet, to date, it is not proven that intra-arterial administration of cytostatic agents has any therapeutic advantage over intra-venous systemic therapy (Bier et al., 1979). At the Department of Oral and Maxillo-facial Surgery, University of Vienna, it is presently still common practice to consider primary carcinoma to be a clear case for surgical intervention. Recent improvement in reconstructive measures greatly favours surgical intervention. Only when tumours have already destroyed the base of the skull or the muscular apparatus of the spine or when the inlet of the thorax has been reached, do we frequently refrain from surgical intervention. In these cases since 1973 we have consistently applied combination therapy, by introducing bleomycin and methotrexate into the tumour-supplying artery, combined with radiotherapy. The purpose of this study was to present results with respect to remission rates and long-term survival.
At the Department of Oral and Maxillo-Facial Surgery, University of Vienna, since 1973, patients have been treated with constant regimens: Methotrexate or bleomycin are administered by means of an intra-arterial catheter which is inserted either retrograde via the superficial temporal artery, the superior thyroid artery or orthograde into the external carotid artery. After the catheter position has been determined angiographically, a daily morning dose of 25 mg methotrexate and 15 mg bleomycin in the evening are infused with a motor driven pump. Infusion duration is 2 hours in both cases. As an antidote to methotrexate, the patient receives an intramuscular dose of 3 mg calcium leucovorin 4 times a day. The daily methotrexate dose is followed by radiation therapy 5 times per week, each dose consisting of 2 Gy. Basically at least 300 mg bleomycin, 5 0 0 m g methotrexate should be administered within 3 weeks and 60 Gy within 6 weeks. The remission rate was assessed 1 month after finishing the therapy. 19 patients had already died before this first assessment of turnout remission. 16 more of the 103 patients could not be included in the study because less than 4 years had elapsed since the end of therapy. So this study only concerns patients treated between 1973 and 1984 (the mean age was 57.5 y; min. 40, max. 75; 80 % within 5 0 - 7 0 years). Among the 68 there were 34 cases of tumour recurrence, which had been pretreated cytostatically, by radiation or surgery. In the paper of Szepesi et al. 1985, and Hollmann et al. 1981 there was no evidence of any statistically significant difference in life expectancy between patients with and those without pretreatment. So we did not a priori separate these two groups. The difficulty in quantifying remission of solid tumours especially in the maxillo-facial area necessitated strict adherence to the following criteria for evaluation purposes. Only in such cases where tumours were not identifiable by clinical means, hence not requiring further therapy, were
Regional Chemotherapy of Inoperable Maxillofacial Tumours
J. Cranio-Max.-Fac. Surg. i8 (1990)
89
Results •- - a - - •
I00
80
•
---o---
CR OVERALL PR NC TG:B no ev.d. TG:B ev.d.
60. 40'
:i
!
2'0
0
!
40
6'0
do
,00
MONTHS
Fig. 1
~ 100
~
Ii 80
\
--,,--
~
~
•
CR OVERALL
PR TG:B no ev.d, In
60 g
40 20
In 36 cases the tumours had already reached a T4NoM0-stage, at the onset of therapy and in 32 cases a T4N1-3M0-stage. With all patients the diagnosis was confirmed histologically. All patients had squamous cell carcinomas of varying degrees of keratinisation. Primary cancer was localized in the maxillary area in 22 patients, 18 patients were affected in the tonsillar region and 16 patients in the area of the tongue and the floor of the mouth. In 10 patients the tumour was located in the lower jaw, in one case in the lips and in another in the cheeks. The average dose of bleomycin administered was 302 mg (max. 495 rag, rain. 125 mg) and the average methotrexate dose was 4 9 4 m g (max. 1072mg, min. 50mg). 57 of 68 patients received the desired therapy dose of 500 mg methotrexate and 300 mg bleomycin and even above this quantity. Also 57 of 68 received 60 Gy of radiotherapy. In 11 cases a mean dose of 30 Gy only could be administered because of prior radiation therapy. 10 cases with complete remission and 34 cases with partial remission were observed, indicating that 65 % responded to combined treatment. On average, complete remission lasted for 48 months (max. 122 months, min. 3 months) and partial remission only for 5 months (max. 10 months, rain. 1 month). The difference in average remission duration is statistically significant (p = 0.0003). Similarly, the difference between median survival time for complete remission (median ST 50months) and partial remission (median ST 14 months) is significant ( p = 0.001). The life table procedure of Kaplan and Meier served to prognosticate a survival time of 1 year for 50 % of the patients, 2 years for 27 %, 3 years for 19 % 4 years for 12 % and 5 years for 10 % (Figs. 1 and 2). Discussion and Conclusions
0
0
i
I
20
40
I
I
I
60
80
100
MONTHS
Fig.2 Fig.l,
2 Life table c o m p a r i s o n of inoperable maxillo-facial malignant tumours, patients (n = 68). CR = complete remission, PR = partial remission, NC = no change•
they considered to be in a state of complete remission (CR). Tumours which showed readily indentifiable regression were considered to be partially remitted (PR). Other cases were termed "no change" (NC). Post therapeutic survical time served as the basis for evaluation of the success of treatment. Statistics
For life table comparison, the Breslow- as well as the Mantel-Cox tests were applied, p ( 0.05 was taken as a significance level.
The application of methotrexate and bleomycin for treatment of malignant tumours in the maxillo-facial area has often been described (Richard et al., 1974; Bilder and Igornova, 1974; Bitter, 1974, and Hollmann et al., 1979). We do not share the view that intra-arterial cytostatic therapy has no measurable advantage over systemic intravenous therapy. We are convinced that local perfusion of cytostatic agents produces a dose increase in the turnout area, whilst action on the periphery is simultaneously reduced; in spite of local side effects of intra-arterial therapy such as ipsilateral mucositis and ipsilateral alopecia. In those 68 patients included in this study, side effects were in no way potentially fatal and were always reversible and moderate. It is widely accepted that this type of cytostatic therapy constitutes a potential danger because methotrexate may cause marrow depression, and pulmonary fibrosis could be caused by bleomycin. The doses applied have never led to fatal bone marrow depression. In 4 instances therapy was discontinued because of thrombocytopoenia and in 2 instances, leucopoenia. Statistical reviews show that pulmonary fibrosis develops in 3 % of all cases when methotrexate is administered in such quantities. In our study not a single case of pulmonary fibrosis was reported.
90
J. Cranio-Max.-Fac. Surg. 18 (1990)
K. Hollmann et al.:Regional Chemotherapy of Inoperable Maxillofacial Tumours
Unilateral mucositis was reported after an average of 17 days in 56 cases and because food intake caused severe pain, alimentation was provided by means of tube feeding in a few cases. A more or less severe unilateral, but completely reversible alopecia was reported in almost all cases. Within an observation period of 5 to 11 years permanent cure was reported in 6 out of 68 patients. Twelve patients survived for at least 2 years after the commencement of therapy. In all, a complete remission was observed in 10 cases, i. e. almost one sixth and in at least half of all cases partial remission could be achieved. The figures show the extent to which survival is influenced in relation to the type of remission. 50 V0 of patients with complete remission still survived after 5 years c o m p a r e d to 3 % with partial remission w h o did not even survive for up to 4 years. N o t a single patient with a progressive or a persistent t u m o u r survived for up to 3 years. An interpretation of these results stresses the importance of achieving complete remission to give a better prognosis. The survival time of patients with partial remission and persistent tumours showed no statistically significant difference. To compare the results with the prognostic index of the DOSAK study (Platz et al., 1982) see life table comparison 1 and 2. Patients of the DOSAK study treatment group B (patients w i t h o u t radical surgical treatment and with alternative therapies) are listed in Table I as TG:B no ev. d., if there was no evidence of disease, TG:B ev. d., if there was evidence of disease after treatment and if lymphnodes were not palpable or clinically negative or clinically positive but movable. In Table 2 we show patients in this study with clinically positive, fixed lymphnodes with and without evidence of disease (TG:B no ev. d., In; TG:B ev. d., In). Table 1 demonstrates a better prognosis for patients with complete remission than for patients with no evidence of disease in the DOSAK t r e a t m e n t group B and a better prognosis for patients with partial remission than for patients of t r e a t m e n t group B with evidence of disease. This is even more obvious in Table 2 where the estimated survival rates of the DOSAK patients with positive fixed lymphnodes are displayed. Since we do not k n o w the patient data to c o m p a r e with our own we cannot check statistical significance in these differences.
Berdal, P.: Gann monograph on cancer research, No. 19. Fundamental and clinical studies of bleomycin. University of Tokyo Press 1976 Bier, J., P. Bender, K. Bitter: CO-bleomycin kinetics in normal and turnout-bearing mice after local and systemic administration. J. Max.-Fac. Surg. 7 (1979) 32 Bilder, J., J. Hornova: Synchronized combination of bleomycin and methotrexate in regional chemotherapy of orofacial carcinomas. Neoplasma 21 (1974) 14 Bitter, K.: Erste Ergebnisse der zytostatischen Behandlung von Plattenepithelcarcinomen in der Mundh6hle mit einer Kombination von Methotrexat und Bleomycin. Dtsch. Zahn-, Mund- und Kieferheilk. 60 (1973) 2 Bitter, K.: Immunity suppression by bleomycin and methotrexate combined treatment in patients with epidermoid carcinomas of the oral cavity. J. Max.-Fac. Surg. 2 (1974) 35 Bitter, K.: Bleomycin-methotrexate-chemotherapy in combination with telecobalt-radiation for patients suffering from advanced oral carcinoma. J. Max.-Fac. Surg. 5 (1977) 75 Carter, S. K.: The chemotherapy of head and neck cancer. Semin. Onkol. 4 (1977) 413 Hollmann, K., G. Mailath, J. Kiihbfck, W. Seitz: Combined intraarterial chemotherapy of methotrexate, bleomycin and radiation for advanced inoperable tumors of the head and neck region. 13th International Congress of Chemotherapy, Vienna, 1983. Kongret~band SE 12.1.11-5 Hollmann, K., W. Jesch, J. Kiihlb6ck, J. Dimopoulus: Combined intraarterial chemotherapy and radiation therapy of turnouts in the maxillofacial region. J. Max.-Fac. Surg. 7 (1979) 191 Hollmann, K., G. Mailath, J. Kiihb6ck, W. Seitz: Die Kombinationsbehandlung orofacialer Malignome mit Strahlen und Zytostatika. Z. Stomatol. (1981) 171-177 KapIan, H. S., ILL. S. Doggett, M. A. Bagshaw, T. S. Nelsen: Radiotherapy of advanced head and neck cancer combined with intraarterial infusion of chemotherapeutic or radiosensitizing agents. In: Proceedings of the international conference on radiation biology and cancer radiation. Society of Japan, Kyoto, Japan (1966) 193 Platz, H., R. Fries, M. Hudec: Therapieabhfingiger Prognoseindex TPI. D6sak, Lienz-Wien 1982 Richard, J. M., H. Sancho, Y. Lepintre, J. Radory, B. Pierquin: Intraarterial chemotherapy and telecobalt therapy in cancer of the oral cavity and oropharynx. Cancer 34 (1974) 491 Sakamoto, K., M. Sakha: The effect of Neomycin and its effects combined with radiation on murine squamous carcinoma in vivo. Brit. J. Cancer 30 (1974) 463
References
Arcangeli, G., C. Nervi, R. Righini, G. Creaton, M. A. Mirri, A. Guerra: Combined radiation and drugs: The effect of intraarterial chemotherapy followed by radiotherapy in head and neck cancer. Radiother. Oncol. 1 (1983) 101 Bagshaw, M. A., R. L S. Doggett, K. C. Smith, H. S. Kaplan, T. S. Nelsen" Intraarterial, 5-bromodeoxy-uridine and X-ray therapy. Amer. J. Roentgenol. 99 (1967) 886
Prof. K. Hollmann, M. D., D.M.D. Dept. of Oral and Maxillo-FacialSurgery University Hospital of Vienna Alserstrafle 4 A-I090 Wien Austria
Book Reviews
McGowan, D. A. (Ed.): An Atlas of Minor Oral Surgery. Principles and Practice. 1989. 132 pp. Martin Dunitz Ltd., London. £ 30.This book is aimed principally at dental practitioners and undergraduate dental students. It begins with some general principles of minor oral surgery such as diagnosis and treatment planning, preoperative preparation, the operation and postoperative care, and continues as a step-by-step atlas of the commoner minor oral surgical procedures. Each procedure is illustrated by high quality colour photographs. There is minimal written material making each section
easy to follow. - Unfortunately, some procedures lack important details necessary for the inexperienced practitioner, or student, such as the technique of sectioning impacted third molars, checking for perforations into the maxillary sinus after removal of upper molar and premolar teeth, and orthograde apicectomy as performed in many countries. - Nevertheless, as mentioned in its preface, this book is a good guide to all those who wish to learn, or improve their knowledge of this branch of the surgeons art. R.A.C.A.V.
