- Email: [email protected]
Prostate Brachytherapy in Patients with Inflammatory Bowel Disease
Int. J. Radiation Oncology Biol. Phys., Vol. 40, No. 1, pp. 135–138, 1998 Copyright © 1998 Elsevier Science Inc. Printed in the USA. All rights reserved 0360-3016/98 $19.00 1 .00
PII S0360-3016(97)00583-X
●
Clinical Investigation PROSTATE BRACHYTHERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE ALISON GRANN, M.D.
AND
KENT WALLNER, M.D.
*Brachytherapy Service, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 Purpose: There are minimal data to support the perceived contraindication of radiation therapy in patients with inflammatory bowel disease (IBD). Because of widespread concern about the possibility of radiation-related morbidity in IBD patients, the posttreatment course for 6 patients with a history of IBD who were treated with 125 I prostate implantation for early stage prostate cancer are reported here. Materials and Methods: Six patients with a prior history of IBD and Stage T1c–T2c prostatic carcinoma underwent 125I prostate brachytherapy from 1991–1996. Three patients had Crohn’s disease and three had ulcerative colitis. The treatment plans were designed to treat the preimplant prostatic margin, as defined on planning CT scan, to 150 Gy. No special effort was made to minimize the rectal surface dose. Detailed records were available for all patients, and all patients were interviewed for this report. Follow-up ranged from 1 to 6 years (median: 3.7 years). Results: None of the 6 patients experienced unusual or significant gastrointestinal side effects following implantation. All 6 patients remain free of GI complications. The rectal surface area that received >100 Gy was kept below 10 mm2 in all patients, in accordance with previously published guidelines. Conclusions: Based on the limited information available, it appears that prostate brachytherapy is safe in patients with a history of IBD. © 1998 Elsevier Science Inc. Prostatic carcinoma, Brachytherapy, Inflammatory bowel disease, Crohn’s, Ulcerative colitis.
INTRODUCTION
advised to have brachytherapy, the rationale being that less rectal surface area would be radiated, perhaps decreasing the likelihood of radiation complications. The posttreatment course for 6 patients with a history of IBD who were treated with 125I prostate brachytherapy for early stage prostate cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1991–1996 are reported here.
‘‘Inflammatory bowel disease’’ (IBD) includes both ulcerative colitis and regional enteritis (Crohn’s disease). Both are chronic, idiopathic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is more prevalent than Crohn’s disease, the prevalence of the former being approximately 1 in 1000 and the latter 3 in 10,000. IBD is more common in caucasians, with a 3– 6-fold increased incidence in Jews over that in nonJews (3). It has been written that IBD is a relative contraindication to pelvic irradiation (1, 2, 5, 8). Despite frequent admonitions against radiation in IBD patients, published reports regarding radiation results in patients with IBD are sparse (5). There is only a single mention of a bowel complication from external beam radiation (EBRT) in IBD patients with prostate cancer (6). Given the perceived contraindication of radiation therapy in this group of patients, there has been some reluctance at our institution to recommend external beam radiation (EBRT) for prostate cancer patients with IBD. Prostate cancer patients with IBD have generally been
METHODS Six patients with a prior history of IBD were treated with I permanent prostate implants at MSKCC from 1991– 1996. They all had adenocarcinoma of the prostate, stages T1c–T2c. Three patients had Crohn’s disease and three had ulcerative colitis. All had been evaluated by a gastroenterologist, and were still followed by their gastroenterologist at the time of referral for 125I implantation. The treatment plans were designed to treat the preimplant prostatic margin, as defined on planning CT scan, to 150 Gy. No special effort was made to minimize the rectal 125
Reprint requests to: Kent Wallner, M.D., Department of Veterans Affairs, VA Puget Sound Health Care System, Radiation Oncology
Service, 1660 S. Columbian Way (174), Seattle, WA 98108-1537. Accepted for publication 28 July 1997.
135
136
I. J. Radiation Oncology
●
Biology
●
Physics
Volume 40, Number 1, 1998
his first colon cancer and a right hemicolectomy at age 63 for a second colon cancer. He has been on sulfasalazine since age 63, having 3– 4 bowel movements each morning and denies any blood in his stool. He was diagnosed with a T1c adenocarcinoma of the prostate at age 68, and had a 125I implant (MPD of 149 Gy and target coverage of 83%). He had no change in bowel movements in the 2 years following brachytherapy.
Fig. 1. Freedom from radiation-related complications following 125 I brachytherapy for early stage prostatic carcinoma in patients with IBD.
surface dose. The matched peripheral dose (MPD) ranged from 141 to 179 Gy. Postimplant, CT-based dosimetry was performed as previously described (10). Coverage of 80% or more of the postimplant target volume by the prescription dose was considered an adequate implant. Detailed records were available for all patients, and all patients were interviewed for this report. Follow-up ranged from 1 to 6 years (median: 3.7 years). RESULTS None of the 6 patients experienced unusual or significant gastrointestinal side effects following implantation. All 6 patients remain free of GI complications (Fig. 1). No patient needed additional medications to manage side effects. Each case is briefly summarized below. Case #1 WB was diagnosed with ulcerative colitis in 1980 at age 48 when he presented with asymptomatic hematochezia. His disease was limited to the rectum, a biopsy was consistent with ulcerative colitis, and he was begun on Azulfadine.y He had no additional bowel symptoms and continues on sulfasalazine at age 62. He presented with a T2a adenocarcinoma of the prostate. He underwent 125I implant (MPD 179 Gy). Postimplant CT-based dosimetry showed 80% target coverage by the 150 Gy isodose line. Six months after implant, he noted an increased amount of blood in his stool, lasting 2 months and not requiring intervention. Two and a half years after 125I brachytherapy, his ulcerative colitis remains quiescent. His bowel movements are limited to once a day. Case #2 WH was diagnosed with ulcerative colitis (with biopsy) at age 30. He underwent a sigmoid colectomy at age 55 for
Case #3 NT had no diagnosis of IBD prior to his diagnosis of T2c prostatic carcinoma at age 58. He began EBRT and received 23 Gy, after which he developed tenesmus and a bloody mucous discharge. After a 10-day treatment break, radiation was resumed, and he received 45 Gy to the whole pelvis. He again had hematochezia and severe tenesmus, treated with mesalamine enemas and suppositories. A colonoscopy demonstrated acute colitis from the anal verge to 20 cm, consistent with radiation colitis. A colonic biopsy was consistent with ulcerative colitis. This was unusual at such a low dose, with a 1-week treatment break, and the diagnosis of underlying ulcerative colitis was made. He had a 125I implant (MPD: 141 Gy) 5 weeks later. By postimplant CT scan, 80% of the target volume was covered by the 150 Gy isodose line. He is doing well 4 years after brachytherapy and all of his GI symptoms have resolved. Case #4 DP was diagnosed with Crohn’s disease (consistent with biopsy), for which he underwent a hemicolectomy at age 26. He developed recurrent symptoms at age 36, treated successfully with steroids. From that time until his diagnosis of a T2b adenocarcinoma of the prostate at age 61, he was relatively symptom free. He underwent a 125 I implant (MPD 141 Gy). Postimplant target coverage by the 150 Gy isodose line is not available. His posttreatment course was complicated by the development of a
Fig. 2. Scatter plot showing the rectal surface area that receives greater than 100 Gy, vs. the prostatic volume.
Prostatic brachytherapy and IBD
● A. GRANN AND K. WALLNER
137
urethral stricture. He currently needs to self-catheterize for urinary retention to prevent overflow incontinence, but he is without gastrointestinal symptoms, 6 years after implantation. Case #5 WB presented with diarrhea at age 69, lasting 2 weeks. His symptoms recurred 1 year later, lasting 2 months. He underwent a colonoscopy and biopsy that showed severe colitis consistent with Crohn’s disease, with rectal sparing. He was treated with Anusoly and is currently on olsalazine Dipentumy. A repeat colonoscopy showed no active disease. He was diagnosed at that time with T1c prostate cancer and underwent a 125I prostate implant (MPD 210 Gy). Postimplant CT scan showed target coverage of 94%. He denies any unusual bowel or bladder symptoms, at 1 year follow-up. Case #6 LS was diagnosed with Crohn’s disease at age 28, treated with partial ileal resection and prednisone. An intestinal biopsy showed granulomas, consistent with Crohn’s disease. At age 56, he had a recrudescence necessitating temporary ileostomy and prednisone. He was symptom-free and off all medications for 4 years, when he developed a stage T1c prostate carcinoma, treated with a 125I implant (MPD 170 Gy). Postimplant target coverage by the 150 Gy isodose line is not available. For 3 months after implantation, he had mild rectal urgency. Five years after implantation, he has had no other intestinal symptoms. Dosimetry The anterior rectal wall doses were similar to the prescription dose (Fig. 2). The rectal surface area that received .100 Gy was kept below 10 mm2 in all patients, in accordance with previously published guidelines (Fig. 3) (10). Postimplant dosimetry was not available for patient #4 (DP).
DISCUSSION The etiology of IBD may involve chronic inflammation and free radical formation (4, 9). It is conceivable that bowel wall already compromised by chronic inflammation would be at increased risk of radiation damage due to radiation-related vascular compromise, ischemia, and the production of oxygen radicals (9). IBD patients could also be at increased risk for radiation-induced pelvic complications due to prior IBD-related abdominal surgery. Approximately 250,000 cases of prostate cancer were diagnosed in the United States in 1995. Based on general incidence rates, roughly 250 of those patients could be
Fig. 3. Profiles of the maximum rectal dose, as a function of distance from the bladder neck. Small areas of high dose are due to source(s) placed too close to the rectal wall. Data were not available for one patient (DP).
expected to have concomitant IBD. Presumably, many of those patients are referred for prostatectomy, based on unsubstantiated claims that they are at increased risk of radiation complications. To our knowledge, there are only 2 case reports and the mention of 1 case in a series of IBD patients with radiationrelated bowel complications (5–7). The 6 patients reported here were reviewed because of the need for some data regarding prostatic cancer patients with IBD, to provide guidance in choosing between treatment modalities. Although the number of patients reported is small, there is only 1 other case report addressing the use of prostate radiation in a patient with IBD (6). Contrary to what might be expected, none of the IBD patients reported here had significant gastrointestinal symptoms following radiation. One patient with a history of ulcerative colitis noticed some increase in the amount of blood in his stool 6 months after his brachytherapy, resolving without intervention. A second patient with Crohn’s disease complained of mild rectal urgency 3 months after his implant, but his symptoms resolved without intervention. Both patients are without intestinal complaints 2 and 4 years after treatment. A third patient developed a urethral stricture, unlikely to have been related to his Crohn’s disease. The risk of radiation morbidity in patients with IBD may depend on the form of treatment used. With brachytherapy, the irradiated portion of bowel is sharply limited and may decrease the risk of complications. Based on the limited information available, it appears that prostate brachytherapy is safe in patients with a history of IBD.
138
I. J. Radiation Oncology
●
Biology
●
Physics
Volume 40, Number 1, 1998
REFERENCES 1. Choi, K.; Aziz, H.; Rotman, M. Management of gynecologic cancers. New York: Liss, 1983. 2. DeCosse, J.; Rhodes, R.; Wentz, W.; Reagan, J.; Dworkin, H.; Holden, W. The natural history and management of radiation induced injury to the gastrointestinal tract. Ann. Surg. 170: 369 –384; 1969. 3. Glickman, R. Harrison’s principles of internal medicine. New York: McGraw Hill, Inc., 1994. 4. Grisham, M. Oxidants and free radicals in inflammatory bowel disease. Lancet 344:859 – 861; 1994. 5. Hoffman, M.; Kalter, C.; Roberts, W.; Cavanagh, D. Early cervical cancer coexistant with idiopathic inflammatory bowel disease. S. Med. J. 82:905–906; 1989. 6. Leibel, S. A.; Heimann, R.; Kutcher, G. J. Three-dimen-
7. 8. 9. 10.
sional conformal radiation therapy in locally advanced carcinoma of the prostate: preliminary results of a phase I dose-escalation study. Int. J. Radiat. Oncol. Biol. Phys. 26:55– 65; 1993. Schofield, R.; Holden, W.; Carr, N. Bowel disease after radiotherapy. J. Roy. Soc. Med. 76:463– 466; 1983. Snelling, M. Therapeutic radiology. New York: Elsevier Science Inc., 1989. Vliet, A.; Bast, A. Role of reactive oxygen species in intestinal diseases. Free Radical Biol. Med. 12:499 –513; 1992. Wallner, K. E.; Roy, J.; Harrison, L. Dsimetry guidelines to minimize urethral and rectal morbidity following transperineal I-125 prostate brachytherapy. Int. J. Radiat. Oncol. Biol. Phys. 32:465– 471; 1995.
PII S0360-3016(97)00583-X
●
Clinical Investigation PROSTATE BRACHYTHERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE ALISON GRANN, M.D.
AND
KENT WALLNER, M.D.
*Brachytherapy Service, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 Purpose: There are minimal data to support the perceived contraindication of radiation therapy in patients with inflammatory bowel disease (IBD). Because of widespread concern about the possibility of radiation-related morbidity in IBD patients, the posttreatment course for 6 patients with a history of IBD who were treated with 125 I prostate implantation for early stage prostate cancer are reported here. Materials and Methods: Six patients with a prior history of IBD and Stage T1c–T2c prostatic carcinoma underwent 125I prostate brachytherapy from 1991–1996. Three patients had Crohn’s disease and three had ulcerative colitis. The treatment plans were designed to treat the preimplant prostatic margin, as defined on planning CT scan, to 150 Gy. No special effort was made to minimize the rectal surface dose. Detailed records were available for all patients, and all patients were interviewed for this report. Follow-up ranged from 1 to 6 years (median: 3.7 years). Results: None of the 6 patients experienced unusual or significant gastrointestinal side effects following implantation. All 6 patients remain free of GI complications. The rectal surface area that received >100 Gy was kept below 10 mm2 in all patients, in accordance with previously published guidelines. Conclusions: Based on the limited information available, it appears that prostate brachytherapy is safe in patients with a history of IBD. © 1998 Elsevier Science Inc. Prostatic carcinoma, Brachytherapy, Inflammatory bowel disease, Crohn’s, Ulcerative colitis.
INTRODUCTION
advised to have brachytherapy, the rationale being that less rectal surface area would be radiated, perhaps decreasing the likelihood of radiation complications. The posttreatment course for 6 patients with a history of IBD who were treated with 125I prostate brachytherapy for early stage prostate cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1991–1996 are reported here.
‘‘Inflammatory bowel disease’’ (IBD) includes both ulcerative colitis and regional enteritis (Crohn’s disease). Both are chronic, idiopathic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is more prevalent than Crohn’s disease, the prevalence of the former being approximately 1 in 1000 and the latter 3 in 10,000. IBD is more common in caucasians, with a 3– 6-fold increased incidence in Jews over that in nonJews (3). It has been written that IBD is a relative contraindication to pelvic irradiation (1, 2, 5, 8). Despite frequent admonitions against radiation in IBD patients, published reports regarding radiation results in patients with IBD are sparse (5). There is only a single mention of a bowel complication from external beam radiation (EBRT) in IBD patients with prostate cancer (6). Given the perceived contraindication of radiation therapy in this group of patients, there has been some reluctance at our institution to recommend external beam radiation (EBRT) for prostate cancer patients with IBD. Prostate cancer patients with IBD have generally been
METHODS Six patients with a prior history of IBD were treated with I permanent prostate implants at MSKCC from 1991– 1996. They all had adenocarcinoma of the prostate, stages T1c–T2c. Three patients had Crohn’s disease and three had ulcerative colitis. All had been evaluated by a gastroenterologist, and were still followed by their gastroenterologist at the time of referral for 125I implantation. The treatment plans were designed to treat the preimplant prostatic margin, as defined on planning CT scan, to 150 Gy. No special effort was made to minimize the rectal 125
Reprint requests to: Kent Wallner, M.D., Department of Veterans Affairs, VA Puget Sound Health Care System, Radiation Oncology
Service, 1660 S. Columbian Way (174), Seattle, WA 98108-1537. Accepted for publication 28 July 1997.
135
136
I. J. Radiation Oncology
●
Biology
●
Physics
Volume 40, Number 1, 1998
his first colon cancer and a right hemicolectomy at age 63 for a second colon cancer. He has been on sulfasalazine since age 63, having 3– 4 bowel movements each morning and denies any blood in his stool. He was diagnosed with a T1c adenocarcinoma of the prostate at age 68, and had a 125I implant (MPD of 149 Gy and target coverage of 83%). He had no change in bowel movements in the 2 years following brachytherapy.
Fig. 1. Freedom from radiation-related complications following 125 I brachytherapy for early stage prostatic carcinoma in patients with IBD.
surface dose. The matched peripheral dose (MPD) ranged from 141 to 179 Gy. Postimplant, CT-based dosimetry was performed as previously described (10). Coverage of 80% or more of the postimplant target volume by the prescription dose was considered an adequate implant. Detailed records were available for all patients, and all patients were interviewed for this report. Follow-up ranged from 1 to 6 years (median: 3.7 years). RESULTS None of the 6 patients experienced unusual or significant gastrointestinal side effects following implantation. All 6 patients remain free of GI complications (Fig. 1). No patient needed additional medications to manage side effects. Each case is briefly summarized below. Case #1 WB was diagnosed with ulcerative colitis in 1980 at age 48 when he presented with asymptomatic hematochezia. His disease was limited to the rectum, a biopsy was consistent with ulcerative colitis, and he was begun on Azulfadine.y He had no additional bowel symptoms and continues on sulfasalazine at age 62. He presented with a T2a adenocarcinoma of the prostate. He underwent 125I implant (MPD 179 Gy). Postimplant CT-based dosimetry showed 80% target coverage by the 150 Gy isodose line. Six months after implant, he noted an increased amount of blood in his stool, lasting 2 months and not requiring intervention. Two and a half years after 125I brachytherapy, his ulcerative colitis remains quiescent. His bowel movements are limited to once a day. Case #2 WH was diagnosed with ulcerative colitis (with biopsy) at age 30. He underwent a sigmoid colectomy at age 55 for
Case #3 NT had no diagnosis of IBD prior to his diagnosis of T2c prostatic carcinoma at age 58. He began EBRT and received 23 Gy, after which he developed tenesmus and a bloody mucous discharge. After a 10-day treatment break, radiation was resumed, and he received 45 Gy to the whole pelvis. He again had hematochezia and severe tenesmus, treated with mesalamine enemas and suppositories. A colonoscopy demonstrated acute colitis from the anal verge to 20 cm, consistent with radiation colitis. A colonic biopsy was consistent with ulcerative colitis. This was unusual at such a low dose, with a 1-week treatment break, and the diagnosis of underlying ulcerative colitis was made. He had a 125I implant (MPD: 141 Gy) 5 weeks later. By postimplant CT scan, 80% of the target volume was covered by the 150 Gy isodose line. He is doing well 4 years after brachytherapy and all of his GI symptoms have resolved. Case #4 DP was diagnosed with Crohn’s disease (consistent with biopsy), for which he underwent a hemicolectomy at age 26. He developed recurrent symptoms at age 36, treated successfully with steroids. From that time until his diagnosis of a T2b adenocarcinoma of the prostate at age 61, he was relatively symptom free. He underwent a 125 I implant (MPD 141 Gy). Postimplant target coverage by the 150 Gy isodose line is not available. His posttreatment course was complicated by the development of a
Fig. 2. Scatter plot showing the rectal surface area that receives greater than 100 Gy, vs. the prostatic volume.
Prostatic brachytherapy and IBD
● A. GRANN AND K. WALLNER
137
urethral stricture. He currently needs to self-catheterize for urinary retention to prevent overflow incontinence, but he is without gastrointestinal symptoms, 6 years after implantation. Case #5 WB presented with diarrhea at age 69, lasting 2 weeks. His symptoms recurred 1 year later, lasting 2 months. He underwent a colonoscopy and biopsy that showed severe colitis consistent with Crohn’s disease, with rectal sparing. He was treated with Anusoly and is currently on olsalazine Dipentumy. A repeat colonoscopy showed no active disease. He was diagnosed at that time with T1c prostate cancer and underwent a 125I prostate implant (MPD 210 Gy). Postimplant CT scan showed target coverage of 94%. He denies any unusual bowel or bladder symptoms, at 1 year follow-up. Case #6 LS was diagnosed with Crohn’s disease at age 28, treated with partial ileal resection and prednisone. An intestinal biopsy showed granulomas, consistent with Crohn’s disease. At age 56, he had a recrudescence necessitating temporary ileostomy and prednisone. He was symptom-free and off all medications for 4 years, when he developed a stage T1c prostate carcinoma, treated with a 125I implant (MPD 170 Gy). Postimplant target coverage by the 150 Gy isodose line is not available. For 3 months after implantation, he had mild rectal urgency. Five years after implantation, he has had no other intestinal symptoms. Dosimetry The anterior rectal wall doses were similar to the prescription dose (Fig. 2). The rectal surface area that received .100 Gy was kept below 10 mm2 in all patients, in accordance with previously published guidelines (Fig. 3) (10). Postimplant dosimetry was not available for patient #4 (DP).
DISCUSSION The etiology of IBD may involve chronic inflammation and free radical formation (4, 9). It is conceivable that bowel wall already compromised by chronic inflammation would be at increased risk of radiation damage due to radiation-related vascular compromise, ischemia, and the production of oxygen radicals (9). IBD patients could also be at increased risk for radiation-induced pelvic complications due to prior IBD-related abdominal surgery. Approximately 250,000 cases of prostate cancer were diagnosed in the United States in 1995. Based on general incidence rates, roughly 250 of those patients could be
Fig. 3. Profiles of the maximum rectal dose, as a function of distance from the bladder neck. Small areas of high dose are due to source(s) placed too close to the rectal wall. Data were not available for one patient (DP).
expected to have concomitant IBD. Presumably, many of those patients are referred for prostatectomy, based on unsubstantiated claims that they are at increased risk of radiation complications. To our knowledge, there are only 2 case reports and the mention of 1 case in a series of IBD patients with radiationrelated bowel complications (5–7). The 6 patients reported here were reviewed because of the need for some data regarding prostatic cancer patients with IBD, to provide guidance in choosing between treatment modalities. Although the number of patients reported is small, there is only 1 other case report addressing the use of prostate radiation in a patient with IBD (6). Contrary to what might be expected, none of the IBD patients reported here had significant gastrointestinal symptoms following radiation. One patient with a history of ulcerative colitis noticed some increase in the amount of blood in his stool 6 months after his brachytherapy, resolving without intervention. A second patient with Crohn’s disease complained of mild rectal urgency 3 months after his implant, but his symptoms resolved without intervention. Both patients are without intestinal complaints 2 and 4 years after treatment. A third patient developed a urethral stricture, unlikely to have been related to his Crohn’s disease. The risk of radiation morbidity in patients with IBD may depend on the form of treatment used. With brachytherapy, the irradiated portion of bowel is sharply limited and may decrease the risk of complications. Based on the limited information available, it appears that prostate brachytherapy is safe in patients with a history of IBD.
138
I. J. Radiation Oncology
●
Biology
●
Physics
Volume 40, Number 1, 1998
REFERENCES 1. Choi, K.; Aziz, H.; Rotman, M. Management of gynecologic cancers. New York: Liss, 1983. 2. DeCosse, J.; Rhodes, R.; Wentz, W.; Reagan, J.; Dworkin, H.; Holden, W. The natural history and management of radiation induced injury to the gastrointestinal tract. Ann. Surg. 170: 369 –384; 1969. 3. Glickman, R. Harrison’s principles of internal medicine. New York: McGraw Hill, Inc., 1994. 4. Grisham, M. Oxidants and free radicals in inflammatory bowel disease. Lancet 344:859 – 861; 1994. 5. Hoffman, M.; Kalter, C.; Roberts, W.; Cavanagh, D. Early cervical cancer coexistant with idiopathic inflammatory bowel disease. S. Med. J. 82:905–906; 1989. 6. Leibel, S. A.; Heimann, R.; Kutcher, G. J. Three-dimen-
7. 8. 9. 10.
sional conformal radiation therapy in locally advanced carcinoma of the prostate: preliminary results of a phase I dose-escalation study. Int. J. Radiat. Oncol. Biol. Phys. 26:55– 65; 1993. Schofield, R.; Holden, W.; Carr, N. Bowel disease after radiotherapy. J. Roy. Soc. Med. 76:463– 466; 1983. Snelling, M. Therapeutic radiology. New York: Elsevier Science Inc., 1989. Vliet, A.; Bast, A. Role of reactive oxygen species in intestinal diseases. Free Radical Biol. Med. 12:499 –513; 1992. Wallner, K. E.; Roy, J.; Harrison, L. Dsimetry guidelines to minimize urethral and rectal morbidity following transperineal I-125 prostate brachytherapy. Int. J. Radiat. Oncol. Biol. Phys. 32:465– 471; 1995.