- Email: [email protected]
Effective management of treatment-related enteritis during preoperative chemoradiation for locally advanced rectal cancer
Proceedings of the 42nd Annual ASTRO Meeting
Dose (Gyt 5 I0
20 25 30 40
2~'~
225
c~ Small Bowel Volume
p-value (grade 3 vs 0 2 )
Absolute Small Bowel Volume (cc)
p value (grade 3 vs 0-2)
>50% >'25% >- 15% :>10% ->8c~ ->7%
0.002 0.004 0.0006 0.0006 0.004 0.004
--> 200 ~> 150 > 125 :> 100
-<0.000 I <0.0001 <0.0001 <0.0001
Acute and late adverse effects in eombinated treatment of rectal carcinoma with 3-dimensional radiotherapy planning
B. A s a d p o u r ] M.J. Eble,= G. Sroka-Pdrez, I M. F. W a n n e n m a c h e r ]
~Department qf Clinical Radiology, Heidelberg, Germany, "Department ()/' Radiooneology, Aachen, Germany Purpose: Combined radio- and chemotherapy in patients with rectal carcinoma is an established strategy for improvement of local control and survival. To decrease acute and late toxicity 3-dimensional treatment planning offers individual target volume prescription, which may result in a limited dose-volume load to surrounding critical structures. The role of 3-D radiotherapy planning in rectal carcinoma patients was evaluated prospectively.
Patients and Methods: A total of 176 patients with rectal carcinoma (stage II n - 65, stage I I I - 111) had 3-D planned external beam radiotherapy (EBRT, preop, n - 33). In 14 patients microscopically or macroscopically (n = 1) residual disease remained. Radiotherapy was given with 23 MeV photons and patients were positioned on an open table-top device. In preoperative irradiation a dose of 414 Gy was given in 15 patients plus intraoperative radiotherapy (IORT, 10 Gy) and 45 Gy to those with E B R T alone. In postoperative E B R T a dose of 414 Gy or 45 Gy was applied, using large fields in addition to IORT (10 Gy) or EBRT boost(5.4 8 Gy) thereafter. EBRT was combined with either 2 cycles 5-FU/Leucovorin or a 5 week course of protracted venouse infusion of 5-FU alone (n 30). Acute and late gastrointestinal and bladder toxicity was documented according to the CTC score. Results: in all patients a three-field technique covers best the defined target volume (mean volume 1403 ccm). The use of non-coplanar p.a.-field reduced dose-volume load to either small bowel or bladder in only 9% of patients. On average 94% of target volume was covered by the 80% isodose (mean m a x i m u m dose 106%). 34% of those patients with inconspicious small bowel function prior to radiotherapy developped acute adverse reactions (grade I - 18.7%, grade 1I = 14.8%, gradeIII 0.6%). Correlation of small bowel volume covered by the 70% and 90% isodose revealed a trend tor increased mean partial organ volume with increased adverse reactions(90%-isodose: grade 0 - 258ccm, I = 294ccm, II 346ccm), but which was not statistically significant. Six patients (3.4%) suffered from small bowel obstruction requiring surgical intervention, 4 of them with a bridle stricture in the postoperative course. There was no correlation to the mean partial organ volume covered by the 50% or 90% isodose. 7.9% and 3.4% of patients with prior inconspicious miction suffered from respectively grade l and grade II adverse bladder reactions. Partial bladder volume covered by the 90% isodose was significantly increased in patients with grade II reactions (64ccm vs. 40ccm, P - 0.02). No adverse late bladder effects were observed. After a median follow-up time of 34.5 month 53 patients expired recurrent disease (local recurrence n - 6, distant metastases n - 39, combined local and distant failure n - 8) with an overall local tumor control rate of 92%.
Conclusions: The combination of an open table-top device and 3-D radiotherapy planning offers ideal tools for improving treatment results by minimizing acute and late toxicity in multi-modality treatment for rectal carcinoma patients.
228
Effective management of treatment-related enteritis during preoperative chemoradiation for locally advanced rectal cancer
M. Callister, N. Janjan, T. Brown, P. Hoff, R. Wolff, F. Sinicrope, J. Skibber, B. Feig, L. Ellis, K. Hunt, S. Curley, A. Bisanz, P. Evetts, P. Allen. R. Wiatrek, T. Mendoza. S. Wang, C. Cleeland, C. Crane, N. Sanfilippo
The University o[" Texas M.D. Anderson Cancer Center Houston, TX Objective: To assess the effectiveness of a bowel management regimen in controlling acute treatment-related enteritis during preoperative chemoradiation for locally advanced rectal cancer.
Methods and Materials: Preoperative chemoradiation [ctx/xrt] was given to 52 patients for locally advanced rectal cancer. Chemotherapy consisted of 5-fluorouracil given as a continuous infusion of 300 rag/m2 each of the 5 days per week that radiation was prescribed. Pelvic radiation, totaling 45 Gy/18 Gy per fraction, was given with 3-field belly board technique. Using the concomitant boost approach, an additional 7.5 Gy/15 Gy per fraction was given to the tumor volume during the last week of pelvic radiation with a 6-hour interfraction interval. A validated survey regarding bowel management was completed prior to, each week during ctx/xrt, and prior to surgery. A 3-step bowel management program was used to control symptoms during ctx/xrt that included anti-diarrheal agents and an opinid analgesic titrated to effect.
Results: The survey was completed by 94% prior to treatment, 81% during the last 2-weeks of ctx/xrt and 81% prior to surgery. Before the start of ctx/xrt, bowel problems were present in 15% of patients. A m o n g these, 39% had a sense of urgency, 24% had 4 - 6 and 10% had > 6 bowel movements [BM] per day, 18% had narrowed stools, and abnormal bowel habits disrupted activities of daily living [ADL] in 18% of cases. Only 3% reported incontinence of stool. During the last 2 weeks of ctx/xrt, bowel problems were also reported by 15% of patients. At this time, 50% bad a sense of urgency [p - 0.019], 18% had narrowed stools [p - 0.977], and 4% had episodes of incontinence [p = 0.987]. Other parameters also remained unchanged from pre-treatment levels; 17% had 4 6 [p - 0.259] and 7.5% had > 6 BM per day [p 0.499], and ADL were impacted in 12.5% of cases [p - 0.170]. Prior to surgery 11% had bowel problems; 43% had a sense of urgency [p - 0.155], 15% narrowed
I. J. Radiation
226
Oncology
0 Biology
l Physics
Volume 48. Number 3, Supplement,
2000
stools [p = 0.6671, 7% had episodes of incontinence [p = 0.8971, 2% had >6 BM per day ]p = 0.1271. and ADL were impacted in IO% of cases [0.247] when compared to pretreatment symptoms. But, only 5% had 4-6 BM per day when compared to pre-treatment symptoms [p = 0.008]. No significant differences were observed for any parameter when preoperative symptoms were compared to symptoms during ctx/xrt. Conclusion: Bowel function can be effectively managed during a course of ctx/xrt for rectal cancer. Other than an increased sense of urgency. no change in bowel function occurred during a course of ctx/xrt using our bowel management regimen. Sign&cant improvement in the frequency of BM was observed before surgery from pretreatment symptom levels. probably because of tumor regression.
229
Acute and late radiotherapy
W. T. Lawrie,’
toxicity in patients with inflammatory
D. S. Song,” R. A. Abrams,’
D. R. Kafonek,’
J. K. Boitnott,’
bowel disease
T. L. DeWeese.’
Purpose: It has been written that radiotherapy (RT) is contraindicated in patients with inflammatory bowel disease (IBD) due to risk of gastrointestinal complications or aggravation of IBD symptoms. However, the available data in the literature regarding this hypothesis are scant, as well as contradictory. The difficulty of estimating the true incidence of RT-related late complications is also confounded by the natural history of IBD, where 17-48% of ulcerative colitis and 90% of Crohn’s patients may eventually require surgical management, The purpose of this study was to evaluate the incidence of gastrointestinal complications in patients with IBD receiving RT. and to identify possible factors associated with these complications. Materials and Methods: Twenty-four patients were identified for the study and their records reviewed. Twenty-three patients had a history of IBD prior to receiving RT to fields encompassing some portion of the gastrointestinal tract (Crohn’s disease) or to the abdomen or pelvis (ulcerative colitis or IBD not otherwise specified): one patient received RT to the chest and was later diagnosed with Crohn’s disease in the colon. Toxicities were graded according to the Radiation Therapy Oncology Group acute and late radiation morbidity criteria. Results: Fifteen patients had Crohn’s disease (CD). 7 ulcerative colitis (UC), and 2 IBD not otherwise specitied. Median follow-up was I2 months (I to 137 months). Median dose received was 4500 cGy (900-7020 cGy): dose could not be determined for one patient with CD treated for malignant thymoma. Sixteen of 24 patients received chemotherapy concurrently with RT. Six of 24 patients (25%) experienced Grade 3 or 4 acute gastrointestinal toxicity; all 6 received concurrent chemotherapy. One patient required early termination of therapy due to severe diarrhea after receiving 2880 cGy to a pelvic field. and underwent surgical diversion one month later due to persistent symptoms. No patient developed exacerbation of IBD symptoms outside the treated area. Four of 24 patients (17%) experienced Grade 3 or 4 late gastrointestinal toxicity. Three patients developed small bowel obstruction requiring surgical intervention 446 months following RT: one of these patients had received RT to the cheat. Another patient developed esophageal stricture requiring percutaneous gastrostomy tube IO months following surgery and RT for advanced laryngeal cancer. There were no significant correlations between complications and IBD type (CD vs UC), prior IBD-related surgery. use of medications for IBD. or status of IBD (active vs inactive). Occurrence of acute complication was significantly associated with occurrence of a late complication (p = 0.017). Conclusions: Patients with IBD may have an increased risk for severe acute RT-related gastrointestinal complications that is more modest than generally perceived: all patients who had Grade 3 or 4 acute complications in this study had received concurrent chemotherapy (p = 0.033). Further study is needed to assess this risk, as well as the impact of RT on these patients’ future gastrointestinal morbidity.
230
Th e small bowel position during adjuvant
J. J. Nuyttens. William
J. M. Robertson,
Braumot~~ Hoyirtrl.
radiation
therapy for rectal cancer
D. Yan. A. A. Martinez
Royrl
Otrk, MI
Purpose: Patients with rectal cancer typically have a small bowel study with oral contrast performed, which is used to design treatment helds. The small bowel, however. can change in position during the course of treatment. In this study, treatment planning CT scans were used to determine the position of the small bowel relative to posterior bone landmarks, and weekly CT scans during the treatment were performed to measure motion of small bowel. Materials and Methods: Treatment planning CT scans were reviewed for 29 patients (10 with an abdominoperineal resection (APR). 9 after low anterior resection (LAR), 9 preoperative (Pre-op) and I after wide local excision (WLE)). All were performed using oral contrast, a prone position on a vacuum bag cradle with a cutout area for small bowel exclusion, and instructions to have a full bladder. Ten patients (2 APR, 5 LAR, 2 Pre-op, I WLE) had weekly pelvic CT scans (4-7 per patient) performed in the treatment position, also with small bowel contrast and full bladder instructions. The CT images were registered according to the pelvic bones and the organs of interest were outlined by a physician. Small bowel position was measured on each CT slice in the midline from the anterior edge of the vertebral body (L5 to coccyx). Small bowel motion was calculated by subtracting the distance on each CT scan from the mean position. The pelvis in the treatment held was also divided into anatomically detined regions, designated as mid-pelvis and anterior pelvis. Small bowel volume motion inside of each region was assessed. Results: Both the LAR and the Pre-op patients had a significantly greater distance between the sacrum and the small bowel (Table). The standard deviation (SD) of small bowel position on the repeat CT scans was greatest for Pre-op (4.7 cm) and LAR (2.7 cm) patients at 5 and 7.5 cm below the sacral promontory, respectively. Despite weekly reminders to have a full bladder during therapy. there was considerable variation found in bladder volume (range 29-499 cm’: median 130 cm’; SD 132 cm’), with a decrease during the course of treatment, As a consequence, the small bowel volume in the mid-pelvis and anterior pelvis had 237% variation from the mean, partially due to bladder tilling.
Dose (Gyt 5 I0
20 25 30 40
2~'~
225
c~ Small Bowel Volume
p-value (grade 3 vs 0 2 )
Absolute Small Bowel Volume (cc)
p value (grade 3 vs 0-2)
>50% >'25% >- 15% :>10% ->8c~ ->7%
0.002 0.004 0.0006 0.0006 0.004 0.004
--> 200 ~> 150 > 125 :> 100
-<0.000 I <0.0001 <0.0001 <0.0001
Acute and late adverse effects in eombinated treatment of rectal carcinoma with 3-dimensional radiotherapy planning
B. A s a d p o u r ] M.J. Eble,= G. Sroka-Pdrez, I M. F. W a n n e n m a c h e r ]
~Department qf Clinical Radiology, Heidelberg, Germany, "Department ()/' Radiooneology, Aachen, Germany Purpose: Combined radio- and chemotherapy in patients with rectal carcinoma is an established strategy for improvement of local control and survival. To decrease acute and late toxicity 3-dimensional treatment planning offers individual target volume prescription, which may result in a limited dose-volume load to surrounding critical structures. The role of 3-D radiotherapy planning in rectal carcinoma patients was evaluated prospectively.
Patients and Methods: A total of 176 patients with rectal carcinoma (stage II n - 65, stage I I I - 111) had 3-D planned external beam radiotherapy (EBRT, preop, n - 33). In 14 patients microscopically or macroscopically (n = 1) residual disease remained. Radiotherapy was given with 23 MeV photons and patients were positioned on an open table-top device. In preoperative irradiation a dose of 414 Gy was given in 15 patients plus intraoperative radiotherapy (IORT, 10 Gy) and 45 Gy to those with E B R T alone. In postoperative E B R T a dose of 414 Gy or 45 Gy was applied, using large fields in addition to IORT (10 Gy) or EBRT boost(5.4 8 Gy) thereafter. EBRT was combined with either 2 cycles 5-FU/Leucovorin or a 5 week course of protracted venouse infusion of 5-FU alone (n 30). Acute and late gastrointestinal and bladder toxicity was documented according to the CTC score. Results: in all patients a three-field technique covers best the defined target volume (mean volume 1403 ccm). The use of non-coplanar p.a.-field reduced dose-volume load to either small bowel or bladder in only 9% of patients. On average 94% of target volume was covered by the 80% isodose (mean m a x i m u m dose 106%). 34% of those patients with inconspicious small bowel function prior to radiotherapy developped acute adverse reactions (grade I - 18.7%, grade 1I = 14.8%, gradeIII 0.6%). Correlation of small bowel volume covered by the 70% and 90% isodose revealed a trend tor increased mean partial organ volume with increased adverse reactions(90%-isodose: grade 0 - 258ccm, I = 294ccm, II 346ccm), but which was not statistically significant. Six patients (3.4%) suffered from small bowel obstruction requiring surgical intervention, 4 of them with a bridle stricture in the postoperative course. There was no correlation to the mean partial organ volume covered by the 50% or 90% isodose. 7.9% and 3.4% of patients with prior inconspicious miction suffered from respectively grade l and grade II adverse bladder reactions. Partial bladder volume covered by the 90% isodose was significantly increased in patients with grade II reactions (64ccm vs. 40ccm, P - 0.02). No adverse late bladder effects were observed. After a median follow-up time of 34.5 month 53 patients expired recurrent disease (local recurrence n - 6, distant metastases n - 39, combined local and distant failure n - 8) with an overall local tumor control rate of 92%.
Conclusions: The combination of an open table-top device and 3-D radiotherapy planning offers ideal tools for improving treatment results by minimizing acute and late toxicity in multi-modality treatment for rectal carcinoma patients.
228
Effective management of treatment-related enteritis during preoperative chemoradiation for locally advanced rectal cancer
M. Callister, N. Janjan, T. Brown, P. Hoff, R. Wolff, F. Sinicrope, J. Skibber, B. Feig, L. Ellis, K. Hunt, S. Curley, A. Bisanz, P. Evetts, P. Allen. R. Wiatrek, T. Mendoza. S. Wang, C. Cleeland, C. Crane, N. Sanfilippo
The University o[" Texas M.D. Anderson Cancer Center Houston, TX Objective: To assess the effectiveness of a bowel management regimen in controlling acute treatment-related enteritis during preoperative chemoradiation for locally advanced rectal cancer.
Methods and Materials: Preoperative chemoradiation [ctx/xrt] was given to 52 patients for locally advanced rectal cancer. Chemotherapy consisted of 5-fluorouracil given as a continuous infusion of 300 rag/m2 each of the 5 days per week that radiation was prescribed. Pelvic radiation, totaling 45 Gy/18 Gy per fraction, was given with 3-field belly board technique. Using the concomitant boost approach, an additional 7.5 Gy/15 Gy per fraction was given to the tumor volume during the last week of pelvic radiation with a 6-hour interfraction interval. A validated survey regarding bowel management was completed prior to, each week during ctx/xrt, and prior to surgery. A 3-step bowel management program was used to control symptoms during ctx/xrt that included anti-diarrheal agents and an opinid analgesic titrated to effect.
Results: The survey was completed by 94% prior to treatment, 81% during the last 2-weeks of ctx/xrt and 81% prior to surgery. Before the start of ctx/xrt, bowel problems were present in 15% of patients. A m o n g these, 39% had a sense of urgency, 24% had 4 - 6 and 10% had > 6 bowel movements [BM] per day, 18% had narrowed stools, and abnormal bowel habits disrupted activities of daily living [ADL] in 18% of cases. Only 3% reported incontinence of stool. During the last 2 weeks of ctx/xrt, bowel problems were also reported by 15% of patients. At this time, 50% bad a sense of urgency [p - 0.019], 18% had narrowed stools [p - 0.977], and 4% had episodes of incontinence [p = 0.987]. Other parameters also remained unchanged from pre-treatment levels; 17% had 4 6 [p - 0.259] and 7.5% had > 6 BM per day [p 0.499], and ADL were impacted in 12.5% of cases [p - 0.170]. Prior to surgery 11% had bowel problems; 43% had a sense of urgency [p - 0.155], 15% narrowed
I. J. Radiation
226
Oncology
0 Biology
l Physics
Volume 48. Number 3, Supplement,
2000
stools [p = 0.6671, 7% had episodes of incontinence [p = 0.8971, 2% had >6 BM per day ]p = 0.1271. and ADL were impacted in IO% of cases [0.247] when compared to pretreatment symptoms. But, only 5% had 4-6 BM per day when compared to pre-treatment symptoms [p = 0.008]. No significant differences were observed for any parameter when preoperative symptoms were compared to symptoms during ctx/xrt. Conclusion: Bowel function can be effectively managed during a course of ctx/xrt for rectal cancer. Other than an increased sense of urgency. no change in bowel function occurred during a course of ctx/xrt using our bowel management regimen. Sign&cant improvement in the frequency of BM was observed before surgery from pretreatment symptom levels. probably because of tumor regression.
229
Acute and late radiotherapy
W. T. Lawrie,’
toxicity in patients with inflammatory
D. S. Song,” R. A. Abrams,’
D. R. Kafonek,’
J. K. Boitnott,’
bowel disease
T. L. DeWeese.’
Purpose: It has been written that radiotherapy (RT) is contraindicated in patients with inflammatory bowel disease (IBD) due to risk of gastrointestinal complications or aggravation of IBD symptoms. However, the available data in the literature regarding this hypothesis are scant, as well as contradictory. The difficulty of estimating the true incidence of RT-related late complications is also confounded by the natural history of IBD, where 17-48% of ulcerative colitis and 90% of Crohn’s patients may eventually require surgical management, The purpose of this study was to evaluate the incidence of gastrointestinal complications in patients with IBD receiving RT. and to identify possible factors associated with these complications. Materials and Methods: Twenty-four patients were identified for the study and their records reviewed. Twenty-three patients had a history of IBD prior to receiving RT to fields encompassing some portion of the gastrointestinal tract (Crohn’s disease) or to the abdomen or pelvis (ulcerative colitis or IBD not otherwise specified): one patient received RT to the chest and was later diagnosed with Crohn’s disease in the colon. Toxicities were graded according to the Radiation Therapy Oncology Group acute and late radiation morbidity criteria. Results: Fifteen patients had Crohn’s disease (CD). 7 ulcerative colitis (UC), and 2 IBD not otherwise specitied. Median follow-up was I2 months (I to 137 months). Median dose received was 4500 cGy (900-7020 cGy): dose could not be determined for one patient with CD treated for malignant thymoma. Sixteen of 24 patients received chemotherapy concurrently with RT. Six of 24 patients (25%) experienced Grade 3 or 4 acute gastrointestinal toxicity; all 6 received concurrent chemotherapy. One patient required early termination of therapy due to severe diarrhea after receiving 2880 cGy to a pelvic field. and underwent surgical diversion one month later due to persistent symptoms. No patient developed exacerbation of IBD symptoms outside the treated area. Four of 24 patients (17%) experienced Grade 3 or 4 late gastrointestinal toxicity. Three patients developed small bowel obstruction requiring surgical intervention 446 months following RT: one of these patients had received RT to the cheat. Another patient developed esophageal stricture requiring percutaneous gastrostomy tube IO months following surgery and RT for advanced laryngeal cancer. There were no significant correlations between complications and IBD type (CD vs UC), prior IBD-related surgery. use of medications for IBD. or status of IBD (active vs inactive). Occurrence of acute complication was significantly associated with occurrence of a late complication (p = 0.017). Conclusions: Patients with IBD may have an increased risk for severe acute RT-related gastrointestinal complications that is more modest than generally perceived: all patients who had Grade 3 or 4 acute complications in this study had received concurrent chemotherapy (p = 0.033). Further study is needed to assess this risk, as well as the impact of RT on these patients’ future gastrointestinal morbidity.
230
Th e small bowel position during adjuvant
J. J. Nuyttens. William
J. M. Robertson,
Braumot~~ Hoyirtrl.
radiation
therapy for rectal cancer
D. Yan. A. A. Martinez
Royrl
Otrk, MI
Purpose: Patients with rectal cancer typically have a small bowel study with oral contrast performed, which is used to design treatment helds. The small bowel, however. can change in position during the course of treatment. In this study, treatment planning CT scans were used to determine the position of the small bowel relative to posterior bone landmarks, and weekly CT scans during the treatment were performed to measure motion of small bowel. Materials and Methods: Treatment planning CT scans were reviewed for 29 patients (10 with an abdominoperineal resection (APR). 9 after low anterior resection (LAR), 9 preoperative (Pre-op) and I after wide local excision (WLE)). All were performed using oral contrast, a prone position on a vacuum bag cradle with a cutout area for small bowel exclusion, and instructions to have a full bladder. Ten patients (2 APR, 5 LAR, 2 Pre-op, I WLE) had weekly pelvic CT scans (4-7 per patient) performed in the treatment position, also with small bowel contrast and full bladder instructions. The CT images were registered according to the pelvic bones and the organs of interest were outlined by a physician. Small bowel position was measured on each CT slice in the midline from the anterior edge of the vertebral body (L5 to coccyx). Small bowel motion was calculated by subtracting the distance on each CT scan from the mean position. The pelvis in the treatment held was also divided into anatomically detined regions, designated as mid-pelvis and anterior pelvis. Small bowel volume motion inside of each region was assessed. Results: Both the LAR and the Pre-op patients had a significantly greater distance between the sacrum and the small bowel (Table). The standard deviation (SD) of small bowel position on the repeat CT scans was greatest for Pre-op (4.7 cm) and LAR (2.7 cm) patients at 5 and 7.5 cm below the sacral promontory, respectively. Despite weekly reminders to have a full bladder during therapy. there was considerable variation found in bladder volume (range 29-499 cm’: median 130 cm’; SD 132 cm’), with a decrease during the course of treatment, As a consequence, the small bowel volume in the mid-pelvis and anterior pelvis had 237% variation from the mean, partially due to bladder tilling.