- Email: [email protected]
High dose-rate interstitial radiotherapy for carcinoma of the endometrium
ABSTRACTS
687
on survival; in particular the survival of patients who had small cell carcinoma are similar to those of other carcinomas. Dose had no influence on SR or MS.
series, no correlation between arterial oxygen content and tumour response was found. It would seem therefore that lung function is not a significant factor moderating radiation response.
SURVEILLANCE CT SCANNING OF THE BRAIN IN PATIENTS WITH SMALL CELL CARCINOMA OF THE BRONCHUS
G. R. CHERRYMAN, M. P. WILLIAMS, J. E. HUSBAND and I. E. SMITH
LATE MORBIDITY OF CHEMOTHERAPY PRECEDING RADIOTHERAPY FOR ADVANCED CARCINOMA OF THE CERVIX N. D, JAMES and H. E. L A M B E R T
Royal Marsden Hospital, Sutton, Surrey
Hammersmith Hospital, London
Patients with small cell carcinoma of the bronchus are at high risk of developing intracerebral metastases. The morbidity from symptomatic intracerebral metastases is great. We have undertaken a prospective study of regular CT brain scanning in a group of 134 patients with small cell carcinoma of the bronchus to see whether CT scanning can detect asymptomatic intracerebral metastases and to determine whether earlier treatment at this stage will reduce the morbidity from central nervous system disease. Contrast-enhanced CT scans were obtained at presentation and subsequently at 3 month intervals in asymptomatic patients or sooner if the patients became symptomatic. Surveillance CT detected metastases in 50 patients. Sixty-two per cent of these patients were asymptomatic and their intracerebral metastases were typically 1-2 cm in diameter when detected. Those patients who became symptomatic on surveillance had larger metastases, usually greater than 2 cm in diameter, and there was often associated peritumoral oedema. The results of clinical follow-up and outcome of disease in these groups of patients will be presented.
In the treatment of advanced carcinoma of the cervix there has recently been great interest in the investigation of the value of cytotoxic chemotherapy in conjunction with radiotherapy. To assess the possible long-term effects of such combined therapy we have retrospectively analysed 36 patients (median age 47, range 34-75 years) treated with chemotherapy prior to radical radiotherapy between 1980 and 1987. The patients all had advanced disease (Stage 1B, n=6; 2A, n = l ; 2B, n = l l ; 3, n=14; 4, n=4), sixteen patients had evidence of lymph node spread at the time of diagnosis (all the stage IB and 2A patients were node positive). The chemotherapy regimes used contained one or more of the following drugs: cisplatinum (n=21), bleomycin (n=6), methotrexate (n=21), vincristine (n=2) and ifosphamide (n=3). Twenty-one patients achieved a complete response, four of these patients subsequently relapsed 0.83 to 1.83 years after treatment. Seventeen patients (including two with stage 4 disease) continue in complete remission at a median of 2.41 years posttreatment (range 0.67 to 8.50 years). Median duration of follow-up was 1.57 (range 0.5 to 8.5) years. There was no additional acute toxicity attributable to the combination of the chemo- and radiotherapy. Late effects were not severe. Two patients have developed radiation cystitis and five had chronic bowel problems. In addition, one patient has renal impairment following cisplatinum therapy. We conclude that the addition of chemotherapy to radical radiotherapy does not result in an increase in late toxicity above that expected with radiotherapy.
RADIOLOGICAL FOLLOW-UP OF CONTINUOUS, HYPERFRACTIONATED RADIOTHERAPY IN NON-SMALL CELL CARCINOMA OF THE BRONCHUS
A-W. AYOUB, E. LYNN, M. SAUNDERS and S. DISCHE
Mount Vernon Hospital, London Fifty-two patients with inoperable carcinoma of the bronchus confined to the chest were treated by radiotherapy, involving three fractions per day given over 12 consecutive days (including weekends). A total dose of 54 Gy was achieved in 36 fractions. Before treatment, patients were fully assessed by clinical examination, chest radiograph, CT scan, bronchoscopy, and in some cases mediastinoscopy. A histological diagnosis was obtained by sputum cytology, bronchoscopy or percutaneous needle biopsy. Some patients had an exploratory thoracotomy. Treated patients were followed up for up to 3 years. Follow-up included clinical examination, chests radiograph, CT scans, and routine biochemical, haematological and bacteriological tests. When necessary, repeat bronchoscopy/oesophagoscopy and/or barium studies were performed. When indicated, bronchoscopic, fluoroscopically guided, or CT-guided percutaneous needle biopsies were performed. The response of the tumour and the lung to treatment is described. The relative values of the chest radiograph, the CT scan and the interventional procedures are assessed. Comparison is made with reported results of conventional radiotherapy schedules. LUNG FUNCTION AND RADIATION RESPONSE A. HONG, S. DISCHE, M. SAUNDERS and P. LOCKWOOD
Mount Vernon Hospital, London Radioresistance resulting from hypoxia has long been recognised. The influence of anaemia on radiation response in normal and tumour tissues has also been demonstrated. Little attention has been given to the problem of increased hypoxia in patients with impaired respiratory function, a common problem, particularly in those with tobaccorelated tumours. Poor pulmonary function in conjunction with anaemia will increase hypoxia and may adversely affect radiation response. If there is impaired lung function so that haemoglobin is not saturated with oxygen when it reaches the tumour, then the effect would be as if there were anaemia. We have performed lung function studies and arterial oxygen saturation levels in a series of 110 patients with advanced tumours of the bronchus and head and neck to determine whether lung function affects radiation response. Although some patients showed an impairment of lung function, haemoglobin saturation levels were rarely below 90%, so it appears that these patients were capable of fully saturating haemoglobin with oxygen. It has been reported that the arterial oxygen content is an important factor in determining tumour response to radiation therapy. In our
ENDOMETRIAL CARCINOMA: A REPORT OF 76 PATIENTS TREATED WITH HEYMAN'S CAPSULES
P. D. J. H A R D M A N and G. G. K H O U R Y
Cookridge Hospital, Leeds Seventy-six patients with carcinoma of the endometrium were treated at Cookridge Hospital between 1970 and 1986 using Heyman's capsules. These patients were not suitable for surgery because of advanced age, obesity or other serious medicfil conditions which precluded hysterectomy. The median age at presentation was 75 years (range 50-93). In three patients the procedure was abandoned due to uterine perforation at the time of cervical dilatation (two patients) and unsatisfactory distribution of capsules (one patient). Forty-nine patients had two insertions separated by 3-5 weeks of whom nine patients also received external beam pelvic irradiation (RT). Twenty-four patients received one insertion of Heyman's capsules of whom 13 also received RT. The median follow-up period was 23 months (range 1-130). Two patients died of anaesthetic complications, 18 died of recurrent cancer at a median interval of 16 months (range 3-42). Fifty-six patients had no evidence of recurrent tumour at the time of last follow-up (38) or at the time of death due to unrelated medical causes (18). The median follow-up for the living patients was 261/2 months. Despite the advanced age of most of these patients, the treatment was well tolerated. An analysis of these results will be presented. HIGH DOSE-RATE INTERSTITIAL RADIOTHERAPY FOR CARCINOMA OF THE ENDOMETRIUM
H. THOMAS, D. PICKERING, J. S. W. STEWART and H. E. LAMBERT
Hammersmith Hospital, London We have used the Buchler high dose-rate remote afterloading system to treat carcinoma of the endometrium and assessed patients with Stage I and II disease treated with surgery, followed by radiotherapy, between January 1980 and May 1986. Patients with early disease received intracavitary treatment only, all others received prior external beam radiotherapy. Until October 1983 intracavitary radiotherapy involved two caesium-containing ovoids and thereafter the study system used a vaginal obturator enclosing an iridium source (here the higher dose-rate was compensated by a dose reduction of 40%). There were 52 historical controls and 50 study patients.
688
CLINICAL RADIOLOGY
The groups were comparable with respect to histology, age and stage. The mean follow-up period was 4.3 and 2.6 years, with minor complication rates of 25% (95% confidence limits 13 to 37%) and 16% (95% CL 6 to 26%) in control and study groups, respectively. (This includes one complication in 13 study patients treated with intracavitary radiotherapy only.) The only major complication was one second malignancy in the treatment area and there was no difference in actuarial survival. Treatment was out-patient-based, required minimal analgesia, less radioprotection than alternative isotopes and eliminated the risk to staff of manual afterloading systems. We conclude that the Buchler system is a safe, convenient substitute for other methods without increased recurrence or complication rates. PINEAL GERMINOMAS IN C H I L D H O O D . T R E A T M E N T CONSIDERATIONS
D. JENKIN, H. CHAN, M. G R E E N B E R G , B. HENDRICK, H. HOFFMAN, R. HUMPHREYS, M. SONLEY and S. WEITZMAN
The Hospital for Sick Children, Toronto, Canada From 1959 through 1986, 50 consecutive children were diagnosed as having a pineal region tumour at the Hospital for Sick Children. A tissue diagnosis was available in 35 of 50 (70%). Thirty-one children were treated as having a germinoma, 21 from the biopsy era and 10 from the pre-biopsy era. Four of 31 (13%) patients had tumour at additional local sites (suprasellar two patients, thalamic two patients). Seven of 31 (23%) had diabetes insipidus at diagnosis. In 27 of 31 (88%) a shunt was required. In 10 of 18 (55%) biopsied patients a partial or subtotal tumour resection was undertaken. There were no operative deaths. Thirty of 31 (97%) patients were irradiated after surgical treatment. The irradiated volume was local, 11; local+brain, 8; and craniospinal in 10 patients. The 10-year survival and relapse-free survival rates were 90% and 86% respectively for the 21 biopsy era patients. Only the one unirradiated patient died due to tumour progression. Spinal relapse occurred in two of 19 (11%) patients who received less than craniospinal irradiation. Both were salvaged from relapse. For the pre-biopsy era 'germinomas' (n=10) survival and relapse-free survival rates at 10 years were 89% and 78% respectively. Two patients suffered late local relapse and chronic progression of local disease to die 8 and 10 years from diagnosis. This form of progression virtually excludes germinoma as the appropriate diagnosis. Overall we have no confirmed example of death due to progressive germinoma among 30 irradiated patients. It is difficult to justify the overall intensification of treatment that has occurred over the years in this highly curable tumour. New treatment proposals will be made.
R A D I O T H E R A P Y FOR E P I D E R M O I D ANAL C A R C I N O M A
D. OTIM-OYET, A. HORWICH, J. CROW, H. T. FORD and C. FISHER
Royal Marsden Hospital, Sutton, Surrey A retrospective analysis on 75 patients treated at the Royal Marsden Hospital between 1958 and 1986 showed that 74.6% presented with Lyons T2 (29) and T3 (27) tumours. Twenty patients (26.6%) had inguinal nodal metastases and three systemic dissemination. Definitive treatment was radiotherapy in 55 patients, 46 of whom received a radical dose of 60 Gy/30#/6 weeks, or NSD equivalent. Four of these had combined modality treatment with 5FU and mitomycin-C. Of 20 patients treated by surgery, nine received pre- or post-operative radiotherapy. Overall the median follow-up of survivors was 49.8 months. The actuarial cause specific survival at 3 years was 55% and this was adversely influenced by increasing stage and histological grade. In the subgroup receiving radical radiotherapy, 26 of 42 (61.9%) evaluable patients achieved primary tumour control. However for T1 T2 NO tumours this rate was 87.5%. Three of five (60%) relapsing patients were salvaged by surgery. Six of 20 (30%) patients treated by surgery recurred locoregionally and none were salvaged by radiotherapy. Eight of 13 (61.5%) patients developing distant metastases also had uncontrolled primary tumours. It is concluded that radiotherapy alone is effective treatment for small epidermoid anal carcinomata, and has the advantage of preserving anal continence. More advanced tumours probably require combined modality treatment. THE I M P O R T A N C E OF SET-UP R E P R O D U C I B I L I T Y IN C O N F O R M A T I O N THERAPY
A. T. TATE
Royal Free Hospital, London Computer-aided three-dimensional tumour imaging and target reconstruction is now possible and, using computer-controlled treatment machines, complex radiation dose distributions can be achieved. The exact shaping of these distributions around a target can be confirmed using an anthropomorphic phantom. In practise, however, the final accuracy of spatial dose delivery is dependent upon exact and reproducible patient positioning. The greatest clinical advantage of three-dimensional or conformation therapy is seen when the target is small and lies deep within a body cavity. The standard setting up techniques used for large field conventional therapy are not sufficiently accurate for these long, small diameter targets. Simple, practical methods for improved patient immobilisation and set-up are described and measurements which demonstrate the limits of daily reproducibility are presented. Potential methods of improving the verification of the accurate location of the treatment volume within the patient are discussed.
THE ROLE OF R A D I O T H E R A P Y IN IN-SITU C A R C I N O M A OF THE LARYNX
P. MacLEOD and F. DANIEL
Plymouth General Hospital, Plymouth In the period 1966-1982, 194 patients have been referred to this department for definitive treatment of in-situ (Tis) and invasive squamous carcinomas of the larynx. In-situ lesions represent 10% of this group, (20 patients) stage T1 37%, T2 25% and stages T3 and T4 28% (UICC). We have analysed our results for the treatment of in-situ lesions and present them in comparison to TI, invasive lesions. All patients were treated with megavoltage radiation, Co 60 or 4 MeV photons, using two fields, laterals or anterior obliques, mean size 4.5x4.5 cm. The mean doses given were 1759 ret (Tis lesions) and 1743 r et (T1 lesions). In the Tis group six of 20 patients (30%) failed to achieve local control with radiotherapy. The surgical augmented salvage rate was 90% (18 of 20), one patient dying an intercurrent death and the other still alive, both with uncontrolled primary disease. Twelve of 71 patients (17%) in the T1 group failed local control with radiotherapy. The augmented salvage rate was 94% (68 of 71). Statistically there is no difference between the primary control and augmented salvage rate in the Tis or T1 groups (X2 P>0.2). Overall actuarial survival at 5 and 10 years is 100% and 100% respectively in the Tis group and 96.8% and 92.6% in the T1 group (P=0.275). Five and 10 year actuarial recurrence free survival rates are 78.8% and 69% respectively for the Tis group and 86.1% and 78.4% for the T1 group (P=0,548). In this series we have found that the local control and survival rates are not significantly different for in-situ and stage T1 invasive carcinomas of the larynx and we support the radiotherapeutic approach to the management of in-situ lesions.
THE CLINICAL T O L E R A N C E OF C O M B I N E D • RADIOSENSITISERS Ro 03-8799 AND SR 2508
T. S. M A U G H A N , N. M. BLEEHEN, H. F. V. NEWMAN and P. WORKMAN
Addenbrooke's Hospital, Cambridge The hypoxic ceil radiosensitisers Ro 03-8799 (Pimonidazole) and SR 2508 (Etanidazole) have different clinical toxicities, and therefore combining the two drugs may improve radiosensitisation without increasing toxicity. Ro 03-8799 produces a transient central nervous system syndrome which limits individual doses to i g/m 2while SR 2508 results in a cumulative peripheral neuropathy limiting the total dose to 34 g/m 2 at 2 g/m 2 individual doses. The present study reports the clinical tolerance following multiple doses of 2 g]m2 SR 2508 and 0.75 g/m2 Ro 03-8799 given three times a week. Of 27 patients treated, four have received 15 infusions and all four developed WHO Grade II peripheral neuropathy. No peripheral neuropathy was reported following this dose of SR 2508 alone, therefore some interaction between the drugs in terms of chronic peripheral neurotoxicity does exist. Pharmacokinetic studies confirm this suggestion, as the most significant predictor for the development of peripheral neuropathy is the cumulative area under the curve for Ro 03-8799. The combination at the maximum tolerated dose level produces a single dose sensitiser enhancement ratio of about 1:5. Despite the increased incidence of neurotoxicity compared with SR 2508 alone, an enhanced sensitiser efficacy may be obtained using the two drugs in combination over either drug used alone. This approach may be tested in a randomised setting once the current Phase 3 studies using the two sensitisers individually have been concluded.
687
on survival; in particular the survival of patients who had small cell carcinoma are similar to those of other carcinomas. Dose had no influence on SR or MS.
series, no correlation between arterial oxygen content and tumour response was found. It would seem therefore that lung function is not a significant factor moderating radiation response.
SURVEILLANCE CT SCANNING OF THE BRAIN IN PATIENTS WITH SMALL CELL CARCINOMA OF THE BRONCHUS
G. R. CHERRYMAN, M. P. WILLIAMS, J. E. HUSBAND and I. E. SMITH
LATE MORBIDITY OF CHEMOTHERAPY PRECEDING RADIOTHERAPY FOR ADVANCED CARCINOMA OF THE CERVIX N. D, JAMES and H. E. L A M B E R T
Royal Marsden Hospital, Sutton, Surrey
Hammersmith Hospital, London
Patients with small cell carcinoma of the bronchus are at high risk of developing intracerebral metastases. The morbidity from symptomatic intracerebral metastases is great. We have undertaken a prospective study of regular CT brain scanning in a group of 134 patients with small cell carcinoma of the bronchus to see whether CT scanning can detect asymptomatic intracerebral metastases and to determine whether earlier treatment at this stage will reduce the morbidity from central nervous system disease. Contrast-enhanced CT scans were obtained at presentation and subsequently at 3 month intervals in asymptomatic patients or sooner if the patients became symptomatic. Surveillance CT detected metastases in 50 patients. Sixty-two per cent of these patients were asymptomatic and their intracerebral metastases were typically 1-2 cm in diameter when detected. Those patients who became symptomatic on surveillance had larger metastases, usually greater than 2 cm in diameter, and there was often associated peritumoral oedema. The results of clinical follow-up and outcome of disease in these groups of patients will be presented.
In the treatment of advanced carcinoma of the cervix there has recently been great interest in the investigation of the value of cytotoxic chemotherapy in conjunction with radiotherapy. To assess the possible long-term effects of such combined therapy we have retrospectively analysed 36 patients (median age 47, range 34-75 years) treated with chemotherapy prior to radical radiotherapy between 1980 and 1987. The patients all had advanced disease (Stage 1B, n=6; 2A, n = l ; 2B, n = l l ; 3, n=14; 4, n=4), sixteen patients had evidence of lymph node spread at the time of diagnosis (all the stage IB and 2A patients were node positive). The chemotherapy regimes used contained one or more of the following drugs: cisplatinum (n=21), bleomycin (n=6), methotrexate (n=21), vincristine (n=2) and ifosphamide (n=3). Twenty-one patients achieved a complete response, four of these patients subsequently relapsed 0.83 to 1.83 years after treatment. Seventeen patients (including two with stage 4 disease) continue in complete remission at a median of 2.41 years posttreatment (range 0.67 to 8.50 years). Median duration of follow-up was 1.57 (range 0.5 to 8.5) years. There was no additional acute toxicity attributable to the combination of the chemo- and radiotherapy. Late effects were not severe. Two patients have developed radiation cystitis and five had chronic bowel problems. In addition, one patient has renal impairment following cisplatinum therapy. We conclude that the addition of chemotherapy to radical radiotherapy does not result in an increase in late toxicity above that expected with radiotherapy.
RADIOLOGICAL FOLLOW-UP OF CONTINUOUS, HYPERFRACTIONATED RADIOTHERAPY IN NON-SMALL CELL CARCINOMA OF THE BRONCHUS
A-W. AYOUB, E. LYNN, M. SAUNDERS and S. DISCHE
Mount Vernon Hospital, London Fifty-two patients with inoperable carcinoma of the bronchus confined to the chest were treated by radiotherapy, involving three fractions per day given over 12 consecutive days (including weekends). A total dose of 54 Gy was achieved in 36 fractions. Before treatment, patients were fully assessed by clinical examination, chest radiograph, CT scan, bronchoscopy, and in some cases mediastinoscopy. A histological diagnosis was obtained by sputum cytology, bronchoscopy or percutaneous needle biopsy. Some patients had an exploratory thoracotomy. Treated patients were followed up for up to 3 years. Follow-up included clinical examination, chests radiograph, CT scans, and routine biochemical, haematological and bacteriological tests. When necessary, repeat bronchoscopy/oesophagoscopy and/or barium studies were performed. When indicated, bronchoscopic, fluoroscopically guided, or CT-guided percutaneous needle biopsies were performed. The response of the tumour and the lung to treatment is described. The relative values of the chest radiograph, the CT scan and the interventional procedures are assessed. Comparison is made with reported results of conventional radiotherapy schedules. LUNG FUNCTION AND RADIATION RESPONSE A. HONG, S. DISCHE, M. SAUNDERS and P. LOCKWOOD
Mount Vernon Hospital, London Radioresistance resulting from hypoxia has long been recognised. The influence of anaemia on radiation response in normal and tumour tissues has also been demonstrated. Little attention has been given to the problem of increased hypoxia in patients with impaired respiratory function, a common problem, particularly in those with tobaccorelated tumours. Poor pulmonary function in conjunction with anaemia will increase hypoxia and may adversely affect radiation response. If there is impaired lung function so that haemoglobin is not saturated with oxygen when it reaches the tumour, then the effect would be as if there were anaemia. We have performed lung function studies and arterial oxygen saturation levels in a series of 110 patients with advanced tumours of the bronchus and head and neck to determine whether lung function affects radiation response. Although some patients showed an impairment of lung function, haemoglobin saturation levels were rarely below 90%, so it appears that these patients were capable of fully saturating haemoglobin with oxygen. It has been reported that the arterial oxygen content is an important factor in determining tumour response to radiation therapy. In our
ENDOMETRIAL CARCINOMA: A REPORT OF 76 PATIENTS TREATED WITH HEYMAN'S CAPSULES
P. D. J. H A R D M A N and G. G. K H O U R Y
Cookridge Hospital, Leeds Seventy-six patients with carcinoma of the endometrium were treated at Cookridge Hospital between 1970 and 1986 using Heyman's capsules. These patients were not suitable for surgery because of advanced age, obesity or other serious medicfil conditions which precluded hysterectomy. The median age at presentation was 75 years (range 50-93). In three patients the procedure was abandoned due to uterine perforation at the time of cervical dilatation (two patients) and unsatisfactory distribution of capsules (one patient). Forty-nine patients had two insertions separated by 3-5 weeks of whom nine patients also received external beam pelvic irradiation (RT). Twenty-four patients received one insertion of Heyman's capsules of whom 13 also received RT. The median follow-up period was 23 months (range 1-130). Two patients died of anaesthetic complications, 18 died of recurrent cancer at a median interval of 16 months (range 3-42). Fifty-six patients had no evidence of recurrent tumour at the time of last follow-up (38) or at the time of death due to unrelated medical causes (18). The median follow-up for the living patients was 261/2 months. Despite the advanced age of most of these patients, the treatment was well tolerated. An analysis of these results will be presented. HIGH DOSE-RATE INTERSTITIAL RADIOTHERAPY FOR CARCINOMA OF THE ENDOMETRIUM
H. THOMAS, D. PICKERING, J. S. W. STEWART and H. E. LAMBERT
Hammersmith Hospital, London We have used the Buchler high dose-rate remote afterloading system to treat carcinoma of the endometrium and assessed patients with Stage I and II disease treated with surgery, followed by radiotherapy, between January 1980 and May 1986. Patients with early disease received intracavitary treatment only, all others received prior external beam radiotherapy. Until October 1983 intracavitary radiotherapy involved two caesium-containing ovoids and thereafter the study system used a vaginal obturator enclosing an iridium source (here the higher dose-rate was compensated by a dose reduction of 40%). There were 52 historical controls and 50 study patients.
688
CLINICAL RADIOLOGY
The groups were comparable with respect to histology, age and stage. The mean follow-up period was 4.3 and 2.6 years, with minor complication rates of 25% (95% confidence limits 13 to 37%) and 16% (95% CL 6 to 26%) in control and study groups, respectively. (This includes one complication in 13 study patients treated with intracavitary radiotherapy only.) The only major complication was one second malignancy in the treatment area and there was no difference in actuarial survival. Treatment was out-patient-based, required minimal analgesia, less radioprotection than alternative isotopes and eliminated the risk to staff of manual afterloading systems. We conclude that the Buchler system is a safe, convenient substitute for other methods without increased recurrence or complication rates. PINEAL GERMINOMAS IN C H I L D H O O D . T R E A T M E N T CONSIDERATIONS
D. JENKIN, H. CHAN, M. G R E E N B E R G , B. HENDRICK, H. HOFFMAN, R. HUMPHREYS, M. SONLEY and S. WEITZMAN
The Hospital for Sick Children, Toronto, Canada From 1959 through 1986, 50 consecutive children were diagnosed as having a pineal region tumour at the Hospital for Sick Children. A tissue diagnosis was available in 35 of 50 (70%). Thirty-one children were treated as having a germinoma, 21 from the biopsy era and 10 from the pre-biopsy era. Four of 31 (13%) patients had tumour at additional local sites (suprasellar two patients, thalamic two patients). Seven of 31 (23%) had diabetes insipidus at diagnosis. In 27 of 31 (88%) a shunt was required. In 10 of 18 (55%) biopsied patients a partial or subtotal tumour resection was undertaken. There were no operative deaths. Thirty of 31 (97%) patients were irradiated after surgical treatment. The irradiated volume was local, 11; local+brain, 8; and craniospinal in 10 patients. The 10-year survival and relapse-free survival rates were 90% and 86% respectively for the 21 biopsy era patients. Only the one unirradiated patient died due to tumour progression. Spinal relapse occurred in two of 19 (11%) patients who received less than craniospinal irradiation. Both were salvaged from relapse. For the pre-biopsy era 'germinomas' (n=10) survival and relapse-free survival rates at 10 years were 89% and 78% respectively. Two patients suffered late local relapse and chronic progression of local disease to die 8 and 10 years from diagnosis. This form of progression virtually excludes germinoma as the appropriate diagnosis. Overall we have no confirmed example of death due to progressive germinoma among 30 irradiated patients. It is difficult to justify the overall intensification of treatment that has occurred over the years in this highly curable tumour. New treatment proposals will be made.
R A D I O T H E R A P Y FOR E P I D E R M O I D ANAL C A R C I N O M A
D. OTIM-OYET, A. HORWICH, J. CROW, H. T. FORD and C. FISHER
Royal Marsden Hospital, Sutton, Surrey A retrospective analysis on 75 patients treated at the Royal Marsden Hospital between 1958 and 1986 showed that 74.6% presented with Lyons T2 (29) and T3 (27) tumours. Twenty patients (26.6%) had inguinal nodal metastases and three systemic dissemination. Definitive treatment was radiotherapy in 55 patients, 46 of whom received a radical dose of 60 Gy/30#/6 weeks, or NSD equivalent. Four of these had combined modality treatment with 5FU and mitomycin-C. Of 20 patients treated by surgery, nine received pre- or post-operative radiotherapy. Overall the median follow-up of survivors was 49.8 months. The actuarial cause specific survival at 3 years was 55% and this was adversely influenced by increasing stage and histological grade. In the subgroup receiving radical radiotherapy, 26 of 42 (61.9%) evaluable patients achieved primary tumour control. However for T1 T2 NO tumours this rate was 87.5%. Three of five (60%) relapsing patients were salvaged by surgery. Six of 20 (30%) patients treated by surgery recurred locoregionally and none were salvaged by radiotherapy. Eight of 13 (61.5%) patients developing distant metastases also had uncontrolled primary tumours. It is concluded that radiotherapy alone is effective treatment for small epidermoid anal carcinomata, and has the advantage of preserving anal continence. More advanced tumours probably require combined modality treatment. THE I M P O R T A N C E OF SET-UP R E P R O D U C I B I L I T Y IN C O N F O R M A T I O N THERAPY
A. T. TATE
Royal Free Hospital, London Computer-aided three-dimensional tumour imaging and target reconstruction is now possible and, using computer-controlled treatment machines, complex radiation dose distributions can be achieved. The exact shaping of these distributions around a target can be confirmed using an anthropomorphic phantom. In practise, however, the final accuracy of spatial dose delivery is dependent upon exact and reproducible patient positioning. The greatest clinical advantage of three-dimensional or conformation therapy is seen when the target is small and lies deep within a body cavity. The standard setting up techniques used for large field conventional therapy are not sufficiently accurate for these long, small diameter targets. Simple, practical methods for improved patient immobilisation and set-up are described and measurements which demonstrate the limits of daily reproducibility are presented. Potential methods of improving the verification of the accurate location of the treatment volume within the patient are discussed.
THE ROLE OF R A D I O T H E R A P Y IN IN-SITU C A R C I N O M A OF THE LARYNX
P. MacLEOD and F. DANIEL
Plymouth General Hospital, Plymouth In the period 1966-1982, 194 patients have been referred to this department for definitive treatment of in-situ (Tis) and invasive squamous carcinomas of the larynx. In-situ lesions represent 10% of this group, (20 patients) stage T1 37%, T2 25% and stages T3 and T4 28% (UICC). We have analysed our results for the treatment of in-situ lesions and present them in comparison to TI, invasive lesions. All patients were treated with megavoltage radiation, Co 60 or 4 MeV photons, using two fields, laterals or anterior obliques, mean size 4.5x4.5 cm. The mean doses given were 1759 ret (Tis lesions) and 1743 r et (T1 lesions). In the Tis group six of 20 patients (30%) failed to achieve local control with radiotherapy. The surgical augmented salvage rate was 90% (18 of 20), one patient dying an intercurrent death and the other still alive, both with uncontrolled primary disease. Twelve of 71 patients (17%) in the T1 group failed local control with radiotherapy. The augmented salvage rate was 94% (68 of 71). Statistically there is no difference between the primary control and augmented salvage rate in the Tis or T1 groups (X2 P>0.2). Overall actuarial survival at 5 and 10 years is 100% and 100% respectively in the Tis group and 96.8% and 92.6% in the T1 group (P=0.275). Five and 10 year actuarial recurrence free survival rates are 78.8% and 69% respectively for the Tis group and 86.1% and 78.4% for the T1 group (P=0,548). In this series we have found that the local control and survival rates are not significantly different for in-situ and stage T1 invasive carcinomas of the larynx and we support the radiotherapeutic approach to the management of in-situ lesions.
THE CLINICAL T O L E R A N C E OF C O M B I N E D • RADIOSENSITISERS Ro 03-8799 AND SR 2508
T. S. M A U G H A N , N. M. BLEEHEN, H. F. V. NEWMAN and P. WORKMAN
Addenbrooke's Hospital, Cambridge The hypoxic ceil radiosensitisers Ro 03-8799 (Pimonidazole) and SR 2508 (Etanidazole) have different clinical toxicities, and therefore combining the two drugs may improve radiosensitisation without increasing toxicity. Ro 03-8799 produces a transient central nervous system syndrome which limits individual doses to i g/m 2while SR 2508 results in a cumulative peripheral neuropathy limiting the total dose to 34 g/m 2 at 2 g/m 2 individual doses. The present study reports the clinical tolerance following multiple doses of 2 g]m2 SR 2508 and 0.75 g/m2 Ro 03-8799 given three times a week. Of 27 patients treated, four have received 15 infusions and all four developed WHO Grade II peripheral neuropathy. No peripheral neuropathy was reported following this dose of SR 2508 alone, therefore some interaction between the drugs in terms of chronic peripheral neurotoxicity does exist. Pharmacokinetic studies confirm this suggestion, as the most significant predictor for the development of peripheral neuropathy is the cumulative area under the curve for Ro 03-8799. The combination at the maximum tolerated dose level produces a single dose sensitiser enhancement ratio of about 1:5. Despite the increased incidence of neurotoxicity compared with SR 2508 alone, an enhanced sensitiser efficacy may be obtained using the two drugs in combination over either drug used alone. This approach may be tested in a randomised setting once the current Phase 3 studies using the two sensitisers individually have been concluded.