Radiotherapy and Oncology, 23 (1992) 53-54 © 1992 Elsevier Science Publishers B.V. All rights reserved. 0167-8140/92/$05.00
53
RADION 00936
Short Communication
Dose escalation for stage C (T3) prostate cancer" minimal rectal toxicity observed using conformal therapy Howard M. Sandier 7, Claudia Perez-Tamayo 2, Randall K. Ten Haken 1 and Allen S. Lichter JUniversity of Michigan Medical Center, Department of Radiation Oncology, Ann Arbor, Michigan, and 2St. John's Hospital, Department of Radiation Oncology, 139 N. Penn, Salina, KA 67401, U.S.A. (Received 21 January 1991; revision received 7 October 1991, accepted 24 October 1991)
Methods
Key words: Prostate cancer, stage C (T3); Conformal therapy; External beam radiation therapy; Dose escalation
Summary The treatment of stage C (T3) adenocarcinoma of the prostate using external beam radiation therapy (RT) reportedly achieves clinical local control of approximately 70-80%. A dose relationship to local control has been demonstrated in prostate cancer, although a doserelated increase in complications has also been observed. To determine the maximum dose deliverable to the prostate gland while maintaining an acceptable complication rate, a prospective doseescalation trial using a conformational planning and dose-delivery technique was initiated for patients with stage C (T3) disease. Initial results reported here are encouraging.
Introduction Progress has been made in conformal treatment and dose delivery through the use of CT-based planning and a beam's-eye view (BEV) approach [4]. It has been demonstrated that conformal planning yields refinements in dose distribution with respect to tumor and normal structures at risk for radiation complications when compared with traditional radiotherapy beam arrangements [6]. However, translation of this technology into clinical improvement remains to be demonstrated, representing an obstacle that needs to be removed before general use of intensive planning techniques can be justified. A prospective dose-escalation trial using a CT-based, 3-D treatment planning system and a 6-field technique was initiated in 1987. The trial was limited to patients with stage C (T3) disease because of a high incidence of reported local failure [1] and because of a suggestion of a dose-response relationship for doses greater than 70 Gy for this stage [2].
Twenty patients with stage C (T3) adenocarcinoma have been entered to date, the first beginning treatment in February 1987 and the last in July 1990. The median age at the time of diagnosis was 65.1 years. All patients were treated using the 6-field conformal boost technique as previously described [6]. Patients were placed in a supine position and immobilized with low density, custom cradles. Axial CT images of the patient were obtained while the patient was immobilized in the treatment position. The CT data were entered into a 3-D radiation therapy planning system [4] and nodal, prostate, and seminal vesicle targets were outlined on appropriate axial slices. Customized cerrobend blocks were created based on the 3-dimensional targets, allowing a total 1.0-1.7 cm margin for dose build-up and patient motion. All patients were initially treated to a volume encompassing regional lymph nodes, prostate and seminal vesicles and then treated to a boost volume consisting of the prostate and seminal vesicles. The nodal field arrangement consists of 4 perpendicular, conformally blocked fields: anterior, posterior and opposed laterals. The boost volume was treated with a 6-field technique, 2 laterals and 4 oblique axial fields at +45 ° with respect to the lateral. Fifty percent of the dose was delivered with the laterals and 50 % with the oblique fields (Fig. 1). The dosimetric advantage of this technique results primarily from the use of BEV blocks in the lateral fields when compared to open fields or arcs. A small additional advantage is seen when compared to a BEV-blocked, 4-field boost by replacing the anterior and posterior portals with two sets of opposed oblique fields. Dose to the initial field ranged from 44 to 50.4 Gy and dose to the boost ranged from 24 to 32 Gy, bringing the total dose to 74 to 80.4 Gy. Initially there was a limited variation in dose between patients. Then the first step in a planned, dose-escalation protocol was standardized to 76 Gy and all subsequent patients were treated to that dose. Fraction size was either 1.8 or 2.0 Gy. All patients are alive and analysis is complete through November 15, 1990. Median follow-up is 19 months (range 3 to 45 months). Toxicity was assessed by history and exam, and all episodes of rectal bleeding suspected to be related to radiation toxicity have
Address for correspondence." Howard M. Sandier, M.D., Department of Radiation Oncology, 1500 E. Medical Center Drive, UH B2C490, Box 0010, Ann Arbor, MI 48109, U.S.A.
54 1.0
U I
I
Grade 3,4,5
0.8
I
Ill
II
I
[
[
Grade 1,2
Proportion , ee o! rectal complication
0.6 0.4 0.2 0.0
,
0
,
10
•
,
20
.
,
•
30
,
40
-
50
Time ( m o n t h s ) Fig. 2. Actuarial analysis of rectal complications after radiation therapy on a dose escalation protocol.
Fig. 1. Conformal 6-field boost technique. Three sets of opposing fields, laterals and + 45 ° with respect to the lateral. A block margin of 1.2 cm is demonstrated and the 95 and 70% isodose lines are displayed.
been confirmed endoscopically. Patients without bleeding were not routinely examined endoscopically. Grade 1 rectal toxicity involved asymptomatic rectal bleeding, grade 2 consisted of mild symptoms responding to simple out-patient treatment, grade 3 required minor surgery, grade 4 involved hospitalization or major surgery, and grade 5 represents a fatal complication. Results
Three rectal complications have occurred - two grade 1 and no treatment was required and one grade 2, responding to simple outpatient management. No serious complications of grade 3 or higher have developed. No bladder complications have occurred. The three complications, all intermittent rectal bleeding, developed between 6 and 18 months and yield a 2-year actuarial incidence of 22% (Fig. 2). The three patients with complications have undergone visualization of the lower gastrointestinal tract, and hyperemia, limited to the rectum and without ulceration, was noted. The rectal symptoms were Stable and showed no sign of either progression or improvement. No appreciable worsening of acute side effects was observed in comparison to patients undergoing treatment to standard doses. No relationship between dose and risk of complication was observed within the narrow dose range used. Complications occurred at 79, 76, and 76.4 Gy. Discussion
The treatment ofadenocarcinoma of the prostate with evident extracapsular extension using RT reportedly achieves clinically assessed local control of approximately 7 0 - 8 0 % [1,2]. Actual local tumor sterilization has probably been overestimated due to relative inaccuracies in clinical assessment of the prostate following RT [3]. Regardless of the technique used to assess tumor control, clinical or pathological, there is room for improvement which, in theory, can
be accomplished without significant increases in patient morbidity. Radiation delivered in a manner that allows coverage of the target volume but spares a portion of the rectum, for instance, provides a potential for safe and possibly efficacious dose escalation. The current "standard" radiation dose of approximately 65-70 Gy in 1.8-2.0 Gy/fraction represents a compromise between local control and radiation-induced morbidity. In an analysis of Patterns of Care data, Hanks found that the incidence of in-field recurrence was decreased as dose was increased above 70 Gy, although complications were also increased. The results reported here are encouraging, no serious rectal toxicity has been observed. Although follow-up is relatively short, most observed complications will occur by 24 months [5]. Should the results hold up with further follow-up, we will conclude that 76 Gy is tolerated when delivered as described here, supporting the benefit of the use of 3-dimensional treatment planning. These data suggest that a conformal dose delivery with marked sparing of the posterior rectal wall may allow higher doses of radiation to be delivered with relative safety. References
1 Bagshaw, M. A., Cox, R. S. and Ray, G.R. Status of radiation treatment of prostate cancer at Stanford University. NCI Monographs 7: 47-60, 1988. 2 Hanks, G.E. External-beam radiation therapy for clinically localized prostate cancer: patterns of care studies in the United States. NCI Monographs 7: 75-84, 1988. 3 Kabalin, J. N., Hodge, K.K., McNeal, J. E., Freiha, F. S. and Stamey, T.A. Identification of residual cancer in the prostate following radiation therapy: role of transrectal ultrasound guided biopsy and prostate specific antigen. J. Urol. 142: 326-331, 1989. 4 McShan, D. L., Fraass, B.A. and Lichter, A.S. Full integration of the beam's eye view concept into computerized treatment planning. Int. J. Radiat. Oncol. Biol. Phys. 18: 1489-1494, 1990. 5 Smit, W. G. J. M., Helle, P.A., van Putten, W. L. J., Wijnmaalen, A.J., Seldenrath, J. J. and van der Werf-Messing, B. H.P. Late radiation damage in prostate cancer patients treated by high dose external radiotherapy in relation to rectal dose. Int. J. Radiat. Oncol. Biol. Phys. 18: 23-29, 1990. 6 Ten Haken, R. K., Perez-Tamayo, C., Tesser, R. J., McShan, D. L., Fraass, B. A. and Lichter, A. S. Boost treatment of the prostate using shaped, fixed fields. Int. J. Radiat. Oncol. Biol. Phys 16: 193-200, 1989.
53
RADION 00936
Short Communication
Dose escalation for stage C (T3) prostate cancer" minimal rectal toxicity observed using conformal therapy Howard M. Sandier 7, Claudia Perez-Tamayo 2, Randall K. Ten Haken 1 and Allen S. Lichter JUniversity of Michigan Medical Center, Department of Radiation Oncology, Ann Arbor, Michigan, and 2St. John's Hospital, Department of Radiation Oncology, 139 N. Penn, Salina, KA 67401, U.S.A. (Received 21 January 1991; revision received 7 October 1991, accepted 24 October 1991)
Methods
Key words: Prostate cancer, stage C (T3); Conformal therapy; External beam radiation therapy; Dose escalation
Summary The treatment of stage C (T3) adenocarcinoma of the prostate using external beam radiation therapy (RT) reportedly achieves clinical local control of approximately 70-80%. A dose relationship to local control has been demonstrated in prostate cancer, although a doserelated increase in complications has also been observed. To determine the maximum dose deliverable to the prostate gland while maintaining an acceptable complication rate, a prospective doseescalation trial using a conformational planning and dose-delivery technique was initiated for patients with stage C (T3) disease. Initial results reported here are encouraging.
Introduction Progress has been made in conformal treatment and dose delivery through the use of CT-based planning and a beam's-eye view (BEV) approach [4]. It has been demonstrated that conformal planning yields refinements in dose distribution with respect to tumor and normal structures at risk for radiation complications when compared with traditional radiotherapy beam arrangements [6]. However, translation of this technology into clinical improvement remains to be demonstrated, representing an obstacle that needs to be removed before general use of intensive planning techniques can be justified. A prospective dose-escalation trial using a CT-based, 3-D treatment planning system and a 6-field technique was initiated in 1987. The trial was limited to patients with stage C (T3) disease because of a high incidence of reported local failure [1] and because of a suggestion of a dose-response relationship for doses greater than 70 Gy for this stage [2].
Twenty patients with stage C (T3) adenocarcinoma have been entered to date, the first beginning treatment in February 1987 and the last in July 1990. The median age at the time of diagnosis was 65.1 years. All patients were treated using the 6-field conformal boost technique as previously described [6]. Patients were placed in a supine position and immobilized with low density, custom cradles. Axial CT images of the patient were obtained while the patient was immobilized in the treatment position. The CT data were entered into a 3-D radiation therapy planning system [4] and nodal, prostate, and seminal vesicle targets were outlined on appropriate axial slices. Customized cerrobend blocks were created based on the 3-dimensional targets, allowing a total 1.0-1.7 cm margin for dose build-up and patient motion. All patients were initially treated to a volume encompassing regional lymph nodes, prostate and seminal vesicles and then treated to a boost volume consisting of the prostate and seminal vesicles. The nodal field arrangement consists of 4 perpendicular, conformally blocked fields: anterior, posterior and opposed laterals. The boost volume was treated with a 6-field technique, 2 laterals and 4 oblique axial fields at +45 ° with respect to the lateral. Fifty percent of the dose was delivered with the laterals and 50 % with the oblique fields (Fig. 1). The dosimetric advantage of this technique results primarily from the use of BEV blocks in the lateral fields when compared to open fields or arcs. A small additional advantage is seen when compared to a BEV-blocked, 4-field boost by replacing the anterior and posterior portals with two sets of opposed oblique fields. Dose to the initial field ranged from 44 to 50.4 Gy and dose to the boost ranged from 24 to 32 Gy, bringing the total dose to 74 to 80.4 Gy. Initially there was a limited variation in dose between patients. Then the first step in a planned, dose-escalation protocol was standardized to 76 Gy and all subsequent patients were treated to that dose. Fraction size was either 1.8 or 2.0 Gy. All patients are alive and analysis is complete through November 15, 1990. Median follow-up is 19 months (range 3 to 45 months). Toxicity was assessed by history and exam, and all episodes of rectal bleeding suspected to be related to radiation toxicity have
Address for correspondence." Howard M. Sandier, M.D., Department of Radiation Oncology, 1500 E. Medical Center Drive, UH B2C490, Box 0010, Ann Arbor, MI 48109, U.S.A.
54 1.0
U I
I
Grade 3,4,5
0.8
I
Ill
II
I
[
[
Grade 1,2
Proportion , ee o! rectal complication
0.6 0.4 0.2 0.0
,
0
,
10
•
,
20
.
,
•
30
,
40
-
50
Time ( m o n t h s ) Fig. 2. Actuarial analysis of rectal complications after radiation therapy on a dose escalation protocol.
Fig. 1. Conformal 6-field boost technique. Three sets of opposing fields, laterals and + 45 ° with respect to the lateral. A block margin of 1.2 cm is demonstrated and the 95 and 70% isodose lines are displayed.
been confirmed endoscopically. Patients without bleeding were not routinely examined endoscopically. Grade 1 rectal toxicity involved asymptomatic rectal bleeding, grade 2 consisted of mild symptoms responding to simple out-patient treatment, grade 3 required minor surgery, grade 4 involved hospitalization or major surgery, and grade 5 represents a fatal complication. Results
Three rectal complications have occurred - two grade 1 and no treatment was required and one grade 2, responding to simple outpatient management. No serious complications of grade 3 or higher have developed. No bladder complications have occurred. The three complications, all intermittent rectal bleeding, developed between 6 and 18 months and yield a 2-year actuarial incidence of 22% (Fig. 2). The three patients with complications have undergone visualization of the lower gastrointestinal tract, and hyperemia, limited to the rectum and without ulceration, was noted. The rectal symptoms were Stable and showed no sign of either progression or improvement. No appreciable worsening of acute side effects was observed in comparison to patients undergoing treatment to standard doses. No relationship between dose and risk of complication was observed within the narrow dose range used. Complications occurred at 79, 76, and 76.4 Gy. Discussion
The treatment ofadenocarcinoma of the prostate with evident extracapsular extension using RT reportedly achieves clinically assessed local control of approximately 7 0 - 8 0 % [1,2]. Actual local tumor sterilization has probably been overestimated due to relative inaccuracies in clinical assessment of the prostate following RT [3]. Regardless of the technique used to assess tumor control, clinical or pathological, there is room for improvement which, in theory, can
be accomplished without significant increases in patient morbidity. Radiation delivered in a manner that allows coverage of the target volume but spares a portion of the rectum, for instance, provides a potential for safe and possibly efficacious dose escalation. The current "standard" radiation dose of approximately 65-70 Gy in 1.8-2.0 Gy/fraction represents a compromise between local control and radiation-induced morbidity. In an analysis of Patterns of Care data, Hanks found that the incidence of in-field recurrence was decreased as dose was increased above 70 Gy, although complications were also increased. The results reported here are encouraging, no serious rectal toxicity has been observed. Although follow-up is relatively short, most observed complications will occur by 24 months [5]. Should the results hold up with further follow-up, we will conclude that 76 Gy is tolerated when delivered as described here, supporting the benefit of the use of 3-dimensional treatment planning. These data suggest that a conformal dose delivery with marked sparing of the posterior rectal wall may allow higher doses of radiation to be delivered with relative safety. References
1 Bagshaw, M. A., Cox, R. S. and Ray, G.R. Status of radiation treatment of prostate cancer at Stanford University. NCI Monographs 7: 47-60, 1988. 2 Hanks, G.E. External-beam radiation therapy for clinically localized prostate cancer: patterns of care studies in the United States. NCI Monographs 7: 75-84, 1988. 3 Kabalin, J. N., Hodge, K.K., McNeal, J. E., Freiha, F. S. and Stamey, T.A. Identification of residual cancer in the prostate following radiation therapy: role of transrectal ultrasound guided biopsy and prostate specific antigen. J. Urol. 142: 326-331, 1989. 4 McShan, D. L., Fraass, B.A. and Lichter, A.S. Full integration of the beam's eye view concept into computerized treatment planning. Int. J. Radiat. Oncol. Biol. Phys. 18: 1489-1494, 1990. 5 Smit, W. G. J. M., Helle, P.A., van Putten, W. L. J., Wijnmaalen, A.J., Seldenrath, J. J. and van der Werf-Messing, B. H.P. Late radiation damage in prostate cancer patients treated by high dose external radiotherapy in relation to rectal dose. Int. J. Radiat. Oncol. Biol. Phys. 18: 23-29, 1990. 6 Ten Haken, R. K., Perez-Tamayo, C., Tesser, R. J., McShan, D. L., Fraass, B. A. and Lichter, A. S. Boost treatment of the prostate using shaped, fixed fields. Int. J. Radiat. Oncol. Biol. Phys 16: 193-200, 1989.
