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467 Poster The influence of field size and field position on the radiation response of the rectum of the rat
Posters
Wednesday/Thursday, 18-19 September 2002 S151
4 to 5 patients with a mean of 12.6 punches per patient. A total of 240 core biopsies from 19 patients have been taken. In 33 core biopsies (14%) the original tissue selected from the donor block could not be found (mismatch H&E section and punch). 9 core biopsies (4%) were lost during the procedures. To date we have only stained for Ki67; 80 (33%) out of the 240 core biopsies were not evaluable. The main reason were mismatches (MM), followed by missing core biopsies and biopsies where only a part of the core was present. These were 55%, 32% and 12% of the unevaluable core biopsies, respectively, The main problem encountered so far is the high incidence of MM. These occurred primarily in-core biopsies taken from resections specimens were only few tumor cells remained after the neoadjuvant treatment. The problem of loosing tissue slices was more pronounced after IHC staining than after H&E staining, Conclusion: The use of TMAs is a promising technique, but some adaptations are necessary to make the technique more robust and reproducible. 465
Poster
Chemo-radiotherapy combined with intracavitary hyperthermia for anal cancer: feasibility and long-term results from a phase II randomized trial V. Kouloutias 1,2, G. Plataniotis 1, C. Dardoufas 1, J. Kouvaris 1, C. Gennatas 1, N. Uzunogou 2, L. Vlahos I 1Areteion University Hospital, Radiotherapy, Athens, Greece 2National Technical University, Electrical & Computer Engineering, Athens, Greece Purpose: The aim of this study was to investigate in a randomized way the clinical benefit of addition of intracavitary hyperthermia (ICHT) to a conventional chemo-radiotherapy schedule in patients with T2-T3NOM0 anal cancer. Methods and Materials: Patients were randomly assigned to undergo chemotherapy with 5-FU and Mitomycin-C combined with radiotherapy with (arm A:'] 9 patients) or without ICHT (arm B: 24 patients). A microwave applicator operating at 433 MHz inserting in the anal-rectal cavity was used for ICHT. Patients in both arms received 1000mg/m2/day 5-FU for days 1-4 and days 28-31" plus 15mg/m 2 Mitomycin-C on day 1. Radiotherapy was administered with a dose of 41.4 Gy (1.8 Gy per fraction) plus a booster dose of 14 Gy (2 Gy per fraction), Results: No severe morbidity was noted in both groups, while the incidence of lower-intestine acute reactions was higher in ICHT arm. After a 5-years follow-up, in hyperthermia arm 18/19 patients (94.7%) preserved their anorectal function and avoided the permanent colostomy, while in second arm 16/24 (66.7%) had a sphincter preservation. Local recurrence free surrival time was significantly higher in the ICHT arm (P=0.023, log-rank test), while no significant difference in overall survival was noted, Conclusion: The addition of ICHT to chemo-radiotherapy schedule of anal cancer seems to offer a new effective and safe therapeutic modality, 466
Results: Due to pre-clerking preop ANC was only aqailable in 83 (47%) patients. Postop ANC was performed in 128 (73%) patients. ANC ratio was calculable in 72 (41%) patients. There was no significant association between acute complications and preop ANC (p=0.25) or postop ANC (p=0.45). ANC ratio was significantly higher in patients without complications (p=O.O2). There was no clear relationship between ANC ratio and OTT, field length or age. Logistic regression including ANC ratio, OTT, age and field length showed that ANC ratio (p=0.02) and OTT (p=0.06) might be significant factors. Conclusions: In this retrospective study there appears to be a relationship between the magnitude of postop neutrophil leucocytosis and the absence of acute complications following SCPRT. However, this study is limited by a majority of preoperative full blood counts being taken many days before surgery at pre-clerking. 467
Poster
The influence of field size and field position on the radiation response of the rectum of the rat G.A. Ross, J.W. Hooewe// University of Oxford, Research Institute, The Churchill Hospital, Oxford, Uni ted Kingdom Purpose: In the treatment of pelvic malignancies by radiotherapy, the distal colon is an important dose limiting normal tissue. The present study was designed to examine to importance of both field size and the position of the treatment volume, within and outside the pelvis on the radiation reaction of the rectum and associated structures. Materials and methods: Female Sprague-Dawley rats, 12-16 weeks of age and weighing 260-300g were used. in these studies. Three different irradiation field configurations were used. Two involved the irradiation of either a 20 mm or a 30 mm length of the rectum within the confines of the pelvis, the posterior margins of the fields being based on the anal and vaginal margins, respectively. In both instances the 25 mm wide field included the whole of the urethra but excluded the bladder. The third field 24 mm long and 25 mm wide was outside the pelvis and was based 26 mm proximal to the anal margin. Irradiation also involved part of the urethra, the bladder and the uterus. Results: In the first 30 days after irradiation the incidence of discharge, a reflection of early mucosal denudation was not influenced by field size or position and there was nosignificant differences in the dose produces this effect in 50% of animals (ED50), i.e. 20.8 - 23.6 Gy. However, deaths within the first 30 days were related to field position. The LD50 (+) from urethra compression due to severe rectal submucosal oedema was 24.9 + 0.7 Gy for the 20 mm long pelvic field and 28.6 + 0.8 Gy for the longer field. Ingrowths of squamous epithelium protected the submucosa, and reduced the severity of oedema. No early occurred after comparable doses to the field outside the pelvis. Effects at later times could also be related to field position more than field size. Conclusion: The present findings cannot be explained in terms of a simple normal tissue complication probability model. Indeed complications are more related to anatomical location than to the volume of rectum irradiated.
Poster
Impaired post-operative neutrophil leucocytosis and acute complications following short course preoperative radiotherapy for operable rectal cancer S. Giridharan 1, N. Srihari 1, C. McConkey 2, A. Hartley 1, J.I. Geh 1 1Queen Elizabeth Hospital, Cancer Centre, Birmingham, United Kingdom 2CRC Institute of Cancer Studies, Cfinical Trials Unit, Birmingham, United Kingdom Introduction: In the Dutch Colorectal Cancer Group Trial the 180-day mortality was increased in patients undergoing total mesorectal excision (TME) more than 3 days after the completion of short course preoperative radiotherapy (SCPRT). A similar relationship between time from the first day of SCPRT to surgery (overall treatment time (OTT)) and acute complications was observed in a recent retrospective audit. One proposed explanation for these findings and the relationship of acute complications with age and radiation volume is suppression of the neutrophil leucocytosis normally seen following abdominal surgery. This study aimed to determine the relationship between acute complications within 3 months of SCPRT and perioperative absolute neutrophil counts (ANC). Method: A SCPRT database of 176 patients treated in 1998 and 1999 was used. Preoperative (preop) ANC (48 hours before surgery) and postoperative (postop) ANC (48 hours after surgery) were obtained from haematology archives. A two sample Wilcoxon test was used to compare preop ANC, postop ANC and the ratio postop ANC/preop ANC (ANC ratio) in patients with and without complications. The relationship between these parameters and OTT, age and radiotherapy field length was examined.
468
Poster
Brachytherapy of the rectum for sphincter preservation: results from a prospective cohort of 42 patients L. Grimard 1, H. Stem 2, J. Maroun 3, J. Cygler4 1Ottawa Regional Cancer Centre, Radiation Oncology, Ottawa, Canada 2Ottawa Regional Cance Centre, Surgery, Ottawa, Canada 3Ottawa Regional Cancer Cenre, Medical Oncology, Ottawa, Canada 4Ottawa Regional Cancer Centre, Physics, Ottawa, Canada Purpose: we report the results of 42 patients to evaluate the feasibility, local control and salvage in rectal adenocarcinomas treated with local excision and low dose rate brachytherapy (Ir192). Materials and methods: From 11/89 to 10/01,42 patients were treated in a prospective cohort combining local excision and Ir192 + external beam radiotherapy (EBRT). There were 21 males and 21 females (age: 33.5 to 97.7 years; 21 being over 70 years old). TNM distribution: 8 TINOMO, 22 T2NOM0, 8 T3NOM0, 2 T3NOM1, one T2NOMx, and one T3NOMx, the latter 2 patients having metastatic breast and prostatic cancer. Nineteen tumors were located at the anorectal ring and 23 at the lower or mid-rectum. Seven tumors were well differentiated adenocarcinomas, 27 were moderately differentiated, 5 poorly differentiated, 2 unspecified, and one tumor was an anorectal melanoma. Results: In 4 patients excision was deferred, one patient developed a postoperative fistula and could not have brachytherapy, and 2 patients refused Ir192 after EBRT. At the time of radiotherapy, 4 patients had gross disease:
Wednesday/Thursday, 18-19 September 2002 S151
4 to 5 patients with a mean of 12.6 punches per patient. A total of 240 core biopsies from 19 patients have been taken. In 33 core biopsies (14%) the original tissue selected from the donor block could not be found (mismatch H&E section and punch). 9 core biopsies (4%) were lost during the procedures. To date we have only stained for Ki67; 80 (33%) out of the 240 core biopsies were not evaluable. The main reason were mismatches (MM), followed by missing core biopsies and biopsies where only a part of the core was present. These were 55%, 32% and 12% of the unevaluable core biopsies, respectively, The main problem encountered so far is the high incidence of MM. These occurred primarily in-core biopsies taken from resections specimens were only few tumor cells remained after the neoadjuvant treatment. The problem of loosing tissue slices was more pronounced after IHC staining than after H&E staining, Conclusion: The use of TMAs is a promising technique, but some adaptations are necessary to make the technique more robust and reproducible. 465
Poster
Chemo-radiotherapy combined with intracavitary hyperthermia for anal cancer: feasibility and long-term results from a phase II randomized trial V. Kouloutias 1,2, G. Plataniotis 1, C. Dardoufas 1, J. Kouvaris 1, C. Gennatas 1, N. Uzunogou 2, L. Vlahos I 1Areteion University Hospital, Radiotherapy, Athens, Greece 2National Technical University, Electrical & Computer Engineering, Athens, Greece Purpose: The aim of this study was to investigate in a randomized way the clinical benefit of addition of intracavitary hyperthermia (ICHT) to a conventional chemo-radiotherapy schedule in patients with T2-T3NOM0 anal cancer. Methods and Materials: Patients were randomly assigned to undergo chemotherapy with 5-FU and Mitomycin-C combined with radiotherapy with (arm A:'] 9 patients) or without ICHT (arm B: 24 patients). A microwave applicator operating at 433 MHz inserting in the anal-rectal cavity was used for ICHT. Patients in both arms received 1000mg/m2/day 5-FU for days 1-4 and days 28-31" plus 15mg/m 2 Mitomycin-C on day 1. Radiotherapy was administered with a dose of 41.4 Gy (1.8 Gy per fraction) plus a booster dose of 14 Gy (2 Gy per fraction), Results: No severe morbidity was noted in both groups, while the incidence of lower-intestine acute reactions was higher in ICHT arm. After a 5-years follow-up, in hyperthermia arm 18/19 patients (94.7%) preserved their anorectal function and avoided the permanent colostomy, while in second arm 16/24 (66.7%) had a sphincter preservation. Local recurrence free surrival time was significantly higher in the ICHT arm (P=0.023, log-rank test), while no significant difference in overall survival was noted, Conclusion: The addition of ICHT to chemo-radiotherapy schedule of anal cancer seems to offer a new effective and safe therapeutic modality, 466
Results: Due to pre-clerking preop ANC was only aqailable in 83 (47%) patients. Postop ANC was performed in 128 (73%) patients. ANC ratio was calculable in 72 (41%) patients. There was no significant association between acute complications and preop ANC (p=0.25) or postop ANC (p=0.45). ANC ratio was significantly higher in patients without complications (p=O.O2). There was no clear relationship between ANC ratio and OTT, field length or age. Logistic regression including ANC ratio, OTT, age and field length showed that ANC ratio (p=0.02) and OTT (p=0.06) might be significant factors. Conclusions: In this retrospective study there appears to be a relationship between the magnitude of postop neutrophil leucocytosis and the absence of acute complications following SCPRT. However, this study is limited by a majority of preoperative full blood counts being taken many days before surgery at pre-clerking. 467
Poster
The influence of field size and field position on the radiation response of the rectum of the rat G.A. Ross, J.W. Hooewe// University of Oxford, Research Institute, The Churchill Hospital, Oxford, Uni ted Kingdom Purpose: In the treatment of pelvic malignancies by radiotherapy, the distal colon is an important dose limiting normal tissue. The present study was designed to examine to importance of both field size and the position of the treatment volume, within and outside the pelvis on the radiation reaction of the rectum and associated structures. Materials and methods: Female Sprague-Dawley rats, 12-16 weeks of age and weighing 260-300g were used. in these studies. Three different irradiation field configurations were used. Two involved the irradiation of either a 20 mm or a 30 mm length of the rectum within the confines of the pelvis, the posterior margins of the fields being based on the anal and vaginal margins, respectively. In both instances the 25 mm wide field included the whole of the urethra but excluded the bladder. The third field 24 mm long and 25 mm wide was outside the pelvis and was based 26 mm proximal to the anal margin. Irradiation also involved part of the urethra, the bladder and the uterus. Results: In the first 30 days after irradiation the incidence of discharge, a reflection of early mucosal denudation was not influenced by field size or position and there was nosignificant differences in the dose produces this effect in 50% of animals (ED50), i.e. 20.8 - 23.6 Gy. However, deaths within the first 30 days were related to field position. The LD50 (+) from urethra compression due to severe rectal submucosal oedema was 24.9 + 0.7 Gy for the 20 mm long pelvic field and 28.6 + 0.8 Gy for the longer field. Ingrowths of squamous epithelium protected the submucosa, and reduced the severity of oedema. No early occurred after comparable doses to the field outside the pelvis. Effects at later times could also be related to field position more than field size. Conclusion: The present findings cannot be explained in terms of a simple normal tissue complication probability model. Indeed complications are more related to anatomical location than to the volume of rectum irradiated.
Poster
Impaired post-operative neutrophil leucocytosis and acute complications following short course preoperative radiotherapy for operable rectal cancer S. Giridharan 1, N. Srihari 1, C. McConkey 2, A. Hartley 1, J.I. Geh 1 1Queen Elizabeth Hospital, Cancer Centre, Birmingham, United Kingdom 2CRC Institute of Cancer Studies, Cfinical Trials Unit, Birmingham, United Kingdom Introduction: In the Dutch Colorectal Cancer Group Trial the 180-day mortality was increased in patients undergoing total mesorectal excision (TME) more than 3 days after the completion of short course preoperative radiotherapy (SCPRT). A similar relationship between time from the first day of SCPRT to surgery (overall treatment time (OTT)) and acute complications was observed in a recent retrospective audit. One proposed explanation for these findings and the relationship of acute complications with age and radiation volume is suppression of the neutrophil leucocytosis normally seen following abdominal surgery. This study aimed to determine the relationship between acute complications within 3 months of SCPRT and perioperative absolute neutrophil counts (ANC). Method: A SCPRT database of 176 patients treated in 1998 and 1999 was used. Preoperative (preop) ANC (48 hours before surgery) and postoperative (postop) ANC (48 hours after surgery) were obtained from haematology archives. A two sample Wilcoxon test was used to compare preop ANC, postop ANC and the ratio postop ANC/preop ANC (ANC ratio) in patients with and without complications. The relationship between these parameters and OTT, age and radiotherapy field length was examined.
468
Poster
Brachytherapy of the rectum for sphincter preservation: results from a prospective cohort of 42 patients L. Grimard 1, H. Stem 2, J. Maroun 3, J. Cygler4 1Ottawa Regional Cancer Centre, Radiation Oncology, Ottawa, Canada 2Ottawa Regional Cance Centre, Surgery, Ottawa, Canada 3Ottawa Regional Cancer Cenre, Medical Oncology, Ottawa, Canada 4Ottawa Regional Cancer Centre, Physics, Ottawa, Canada Purpose: we report the results of 42 patients to evaluate the feasibility, local control and salvage in rectal adenocarcinomas treated with local excision and low dose rate brachytherapy (Ir192). Materials and methods: From 11/89 to 10/01,42 patients were treated in a prospective cohort combining local excision and Ir192 + external beam radiotherapy (EBRT). There were 21 males and 21 females (age: 33.5 to 97.7 years; 21 being over 70 years old). TNM distribution: 8 TINOMO, 22 T2NOM0, 8 T3NOM0, 2 T3NOM1, one T2NOMx, and one T3NOMx, the latter 2 patients having metastatic breast and prostatic cancer. Nineteen tumors were located at the anorectal ring and 23 at the lower or mid-rectum. Seven tumors were well differentiated adenocarcinomas, 27 were moderately differentiated, 5 poorly differentiated, 2 unspecified, and one tumor was an anorectal melanoma. Results: In 4 patients excision was deferred, one patient developed a postoperative fistula and could not have brachytherapy, and 2 patients refused Ir192 after EBRT. At the time of radiotherapy, 4 patients had gross disease: