0360-3016/91 $3.00 + .oO Copyright 0 1991 Pergamon Press plc
In1 J. Radialion Oncology RIO/ Phys., Vol. 20, pp. 1379-1382 Pnnted I” the U.S.A. All rights reserved.
??Correspondence
PELVIC
PALLIATION RADIOTHERAPY BLADDER CANCER
OF ADVANCED
Montebello 03 10 Oslo 3, Norway
Curative treatment of bladder cancer is often not possible in patients who present with primary tumours extending beyond the bladder, or in whom high age, decreased performance status, and/or other concomitant chronic diseases do not allow intensive multimodality treatment. Many of these patients suffer from a severely disturbed bladder function (incontinence, dysuria, pollakisutia, hematuria) and are in need of palliative therapy. Moderately dosed radiotherapy is generally believed to represent an ap propriate method to achieve palliation. On the background of the expected short life span and-most important-because of a general shortage of radiotherapy resources palliative radiotherapy in bladder cancer is ohen given by rather simple radiation techniques applying relatively high daily fractions over a short time. Some authors have used single high dose fractions (10 Gy) ( 1). Another frequently applied radiation schedule used 3 Gy daily given over IO days to an anterior and posterior pelvic field. However, except for hematuria, only a few clinical investigators have discussed the effectiveness of palliative pelvic radiotherapy with palliation as an endpoint. From I987 to 1989, we therefore performed a prospective investigation in 39 patients with advanced bladder cancer who were not candidates for curative (high-dose) radiotherapy because of high age (>80 years) and/or distant metastases. Before treatment all patients had disturbances of their bladder function. Radiotherapy was given by linear accellerators (16 MU) to an anterior and posterior pelvic field. A target dose of 30 Gy was given by a daily fraction of 3 Gy (from Monday to Friday). The efficacy of this palliative treatment was assessed by self-administered questionnaires (8) to be completed by the patient before treatment, at treatment discontinuation, and 3 months thereafter. Control cystoscopies were not regularly performed. Based on the patients’ self assessments no improvement could be observed for the pre-treatment urinary symptoms compared to the pretreatment situation except for macroscopic hematuria. The number of patients with highly impaired performance status and/or reduced social activity remained unchanged. The lb-month overall survival was 17%. The selected radiotherapy schedule is thus an ineffective palliation treatment in the majority of patients with advanced bladder cancer. Also other authors (2) have doubted about the value of palliative pelvic irradiation in advanced bladder cancer, but radiotherapy details are often not presented. On the other hand, high-dose single fraction pelvic irradiation may reduce severe hematuria due to bladder cancer (I). Bladder cancer is only moderately radio-sensitive and high radiation doses are required to sterilize a large primary tumour. A target dose of 30 Gy over 10 days is most probably too low to achieve even a transient tumour response and symptomatic relief. Other treatment schedules should be developed which yield a better radiobiologic effect and better palliation results. Accelerated radiotherapy (4) may be a option especially if, in the light of the dismal overall survival, it can be given over a short period. Urinary diversion and/or total cystectomy are other means that are claimed to achieve satisfactory palliation during in the often short lifetime in patients with advanced bladder cancer. In any case, alternative palliative treatment modalities should be investigated in randomized trials where relief of subjective symptoms, as assessed by the patient himself/herself, should be the primary endpoint. We feel that self-administered questionnaire represent a feasible way to assess the effect of palliative radiotherapy in patients with advanced bladder cancer.
Chan, R. C.; Bracken, R. B.; Johnson, D. E. Single dose whole pelvis megavoltage irradiation for palliative control of hematuria or ureteral obstruction. J. Urol. 122:750-751; 1979. Egghart, G.; Altwein, J. E. Palliative therapy in cancer of the bladder: exoerience with 179 oatients (Abstract 259). J. Ural. (part 2) 131: . . . 168A; 1984. Foss& S. D.; Aaronson, N.; Calais da Silva, F.; Denis, L.; Newling, D.; Hosbach, G.; Kaalhus, 0. Quality of life in patients with muscleinfiltrating bladder cancer and hormone-resistant prostatic cancer. Eur. Urol. 16:335-339; 1989. Rugg, T.; Lartigau, E.; Saunders, M. T.; Dische, S. Accelerated radiotherapy and morbidity. Book of Abstracts, 5th European Conference on Clinical Oncology, 3-7 Sept., 1989. HDR IN GYNECOLOGICAL APPLICATIONS: DOSE AND VOLUME CONSIDERATIONS
The article by Van Lancker and Stonne (6) in the previous issue on gynecological applications of HDR brachytherapy highlights the dangers of the implementation of new technologies without adequate preparation, and raises several important questions about dose and volume specification with these treatments. Since I feel that the authors have only partly explained the dangers and how to overcome them, and have only partly answered the dosimetry questions, I would like to present a different interpretation of their results. The treatment technique they initially employed was to give 46-48.6 Gy by AP/PA fields without midline blocking, followed by two HDR intracavitary fractions of 8.5 Gy each to Pt. A, with maximum allowable doses to bladder and rectum of 13 Gy/fraction and 11 Gy/fraction, respectively, from the intracavitary applications. An unacceptably high rate of radiation-induced rectal and bladder injuries resulted. Because of this, the HDR part of the therapy was changed to three fractions of 5 Gy each, with maximum acceptable bladder and rectal doses reduced to 5 Gy/fraction. This seems to have solved the problem of organ injury, but a most important factor is not mentioned, namely, how was it possible to reduce the bladder and rectal doses so significantly? Unfortunately, the answer to this question is not obvious from the information presented in the article, but 1believe a previous paper about these same patients (5) gives us a clue. In this earlier paper, it was stated that no rectal retraction (or, presumably, packing) was used with the first group of patients. I assume that it was the addition of packing and/or retraction that made it possible to reduce bladder and rectal doses so significantly for the second group of patients. I postulate that this lack of retraction/packing in the first patients was a major cause of the high injury rate, and this important message needs to be given to anyone contemplating changing from LDR to HDR therapy for such patients. Of very special concern, again not mentioned in the paper in the previous issue (6) is the need to avoid “hot-spots” which exceed tolerance in bladder and rectal tissues: the earlier paper (5) mentioned that “hotspot” doses to bladder and rectum is some patients were as high as 32 Gy in the two HDR fractions. Using the linear-quadratic (L-Q) model (I), with late-reacting tissue cu/fl = 2.5 Gy, it can be shown that the total extrapolated responses dose (ERD) at these points was as high as 250. ERD’s about half this value are needed in order to keep complication rates acceptable (3). 1 find this issue of “hot-spot” doses to bladder and rectal tissues especially interesting in the Van Lancker and Storme article, since they make the generalized conclusion that the doses at the ICRU bladder and
D. Foss,& Department of Radiotherapy and Medical Oncology The Norwegian Radium Hospital SOPHIE
1379
In1 J. Radialion Oncology RIO/ Phys., Vol. 20, pp. 1379-1382 Pnnted I” the U.S.A. All rights reserved.
??Correspondence
PELVIC
PALLIATION RADIOTHERAPY BLADDER CANCER
OF ADVANCED
Montebello 03 10 Oslo 3, Norway
Curative treatment of bladder cancer is often not possible in patients who present with primary tumours extending beyond the bladder, or in whom high age, decreased performance status, and/or other concomitant chronic diseases do not allow intensive multimodality treatment. Many of these patients suffer from a severely disturbed bladder function (incontinence, dysuria, pollakisutia, hematuria) and are in need of palliative therapy. Moderately dosed radiotherapy is generally believed to represent an ap propriate method to achieve palliation. On the background of the expected short life span and-most important-because of a general shortage of radiotherapy resources palliative radiotherapy in bladder cancer is ohen given by rather simple radiation techniques applying relatively high daily fractions over a short time. Some authors have used single high dose fractions (10 Gy) ( 1). Another frequently applied radiation schedule used 3 Gy daily given over IO days to an anterior and posterior pelvic field. However, except for hematuria, only a few clinical investigators have discussed the effectiveness of palliative pelvic radiotherapy with palliation as an endpoint. From I987 to 1989, we therefore performed a prospective investigation in 39 patients with advanced bladder cancer who were not candidates for curative (high-dose) radiotherapy because of high age (>80 years) and/or distant metastases. Before treatment all patients had disturbances of their bladder function. Radiotherapy was given by linear accellerators (16 MU) to an anterior and posterior pelvic field. A target dose of 30 Gy was given by a daily fraction of 3 Gy (from Monday to Friday). The efficacy of this palliative treatment was assessed by self-administered questionnaires (8) to be completed by the patient before treatment, at treatment discontinuation, and 3 months thereafter. Control cystoscopies were not regularly performed. Based on the patients’ self assessments no improvement could be observed for the pre-treatment urinary symptoms compared to the pretreatment situation except for macroscopic hematuria. The number of patients with highly impaired performance status and/or reduced social activity remained unchanged. The lb-month overall survival was 17%. The selected radiotherapy schedule is thus an ineffective palliation treatment in the majority of patients with advanced bladder cancer. Also other authors (2) have doubted about the value of palliative pelvic irradiation in advanced bladder cancer, but radiotherapy details are often not presented. On the other hand, high-dose single fraction pelvic irradiation may reduce severe hematuria due to bladder cancer (I). Bladder cancer is only moderately radio-sensitive and high radiation doses are required to sterilize a large primary tumour. A target dose of 30 Gy over 10 days is most probably too low to achieve even a transient tumour response and symptomatic relief. Other treatment schedules should be developed which yield a better radiobiologic effect and better palliation results. Accelerated radiotherapy (4) may be a option especially if, in the light of the dismal overall survival, it can be given over a short period. Urinary diversion and/or total cystectomy are other means that are claimed to achieve satisfactory palliation during in the often short lifetime in patients with advanced bladder cancer. In any case, alternative palliative treatment modalities should be investigated in randomized trials where relief of subjective symptoms, as assessed by the patient himself/herself, should be the primary endpoint. We feel that self-administered questionnaire represent a feasible way to assess the effect of palliative radiotherapy in patients with advanced bladder cancer.
Chan, R. C.; Bracken, R. B.; Johnson, D. E. Single dose whole pelvis megavoltage irradiation for palliative control of hematuria or ureteral obstruction. J. Urol. 122:750-751; 1979. Egghart, G.; Altwein, J. E. Palliative therapy in cancer of the bladder: exoerience with 179 oatients (Abstract 259). J. Ural. (part 2) 131: . . . 168A; 1984. Foss& S. D.; Aaronson, N.; Calais da Silva, F.; Denis, L.; Newling, D.; Hosbach, G.; Kaalhus, 0. Quality of life in patients with muscleinfiltrating bladder cancer and hormone-resistant prostatic cancer. Eur. Urol. 16:335-339; 1989. Rugg, T.; Lartigau, E.; Saunders, M. T.; Dische, S. Accelerated radiotherapy and morbidity. Book of Abstracts, 5th European Conference on Clinical Oncology, 3-7 Sept., 1989. HDR IN GYNECOLOGICAL APPLICATIONS: DOSE AND VOLUME CONSIDERATIONS
The article by Van Lancker and Stonne (6) in the previous issue on gynecological applications of HDR brachytherapy highlights the dangers of the implementation of new technologies without adequate preparation, and raises several important questions about dose and volume specification with these treatments. Since I feel that the authors have only partly explained the dangers and how to overcome them, and have only partly answered the dosimetry questions, I would like to present a different interpretation of their results. The treatment technique they initially employed was to give 46-48.6 Gy by AP/PA fields without midline blocking, followed by two HDR intracavitary fractions of 8.5 Gy each to Pt. A, with maximum allowable doses to bladder and rectum of 13 Gy/fraction and 11 Gy/fraction, respectively, from the intracavitary applications. An unacceptably high rate of radiation-induced rectal and bladder injuries resulted. Because of this, the HDR part of the therapy was changed to three fractions of 5 Gy each, with maximum acceptable bladder and rectal doses reduced to 5 Gy/fraction. This seems to have solved the problem of organ injury, but a most important factor is not mentioned, namely, how was it possible to reduce the bladder and rectal doses so significantly? Unfortunately, the answer to this question is not obvious from the information presented in the article, but 1believe a previous paper about these same patients (5) gives us a clue. In this earlier paper, it was stated that no rectal retraction (or, presumably, packing) was used with the first group of patients. I assume that it was the addition of packing and/or retraction that made it possible to reduce bladder and rectal doses so significantly for the second group of patients. I postulate that this lack of retraction/packing in the first patients was a major cause of the high injury rate, and this important message needs to be given to anyone contemplating changing from LDR to HDR therapy for such patients. Of very special concern, again not mentioned in the paper in the previous issue (6) is the need to avoid “hot-spots” which exceed tolerance in bladder and rectal tissues: the earlier paper (5) mentioned that “hotspot” doses to bladder and rectum is some patients were as high as 32 Gy in the two HDR fractions. Using the linear-quadratic (L-Q) model (I), with late-reacting tissue cu/fl = 2.5 Gy, it can be shown that the total extrapolated responses dose (ERD) at these points was as high as 250. ERD’s about half this value are needed in order to keep complication rates acceptable (3). 1 find this issue of “hot-spot” doses to bladder and rectal tissues especially interesting in the Van Lancker and Storme article, since they make the generalized conclusion that the doses at the ICRU bladder and
D. Foss,& Department of Radiotherapy and Medical Oncology The Norwegian Radium Hospital SOPHIE
1379
