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311 poster Prostate specific antigen bounce after hormonal ablation, external beam radiation therapy and high dose rate brachytherapy in the treatment of prostate cancer
Posters
undisturbed growth (n=5) served as controls. Three animals were irradiated per time point and exposure condition. At least two flow cytometrical analyses were carried out per animal. Flow cytometry was performed after 6-diamidino-2-phenylindole (DAPI) staining of disintegrated tumor tissue fragments using a PAS II flow cytometer ( Partec, Germany (. Results: By flow cytometric analysis this tumor consisted of a mixture of diploid and aneuploid cells, with the latter cohort possessing a constant DNAqndex of 1.9 + 0.06. Only the aneuploid cell fraction which mainly represented the tumor population was used for further analysis. Comparison of sham treated (empty tube) and untreated controls did not show a differential effect of tube insertion on cell cycle regulation. Under both treatment modalities (dose 20 Gy) the fraction of aneuploid cells in G2M-phase increased significantly within 48 h (PDR, Mann-Whitney Test p<0.05) and 24 h (CLDR, MannWhitney Test p<0.05) after initiation of therapy. To avoid multiple statistical testing at the different time points the Kolmogorov-Smirnov was used as a non-parametric statistical test to compare the corresponding cell cycle phases of the two treatment arms (e.g. G1 CLDR vs. G1 PDR etc.). Differential effects on cell cycle progression were only found in the G2M fraction after irradiation with 20 Gy (p<0,05). Conclusion: Cell cycle progression represents another important factor beneath incomplete repair when comparing the radiobiological effects of different fractionation schedules. When applying higher doses PDR and CLDR brachytherapy do not effect cell cycle progression differently. These data further expand our mechanistical understanding of PDR and CLDR brachytherapy. 311 poster Prostate specific antigen bounce after hormonal ablation, external beam radiation therapy and high dose rate brachytherapy in the treatment of prostate cancer
R. Ivker ~, B. Low2, A. Helfman 3, S. Shoengolcf , A. Strumeyer ~, W. Chen e, L. Bell z INewark Beth Israel Medical Center, Department of Radiation Oncology, Newark, U.S.A. 2Newark Beth Israel, Division of Medical Oncology, Newark, U.S.A. Purpose: To determine the incidence of the phenomenon known as prostate specific antigen (PSA) bounce in prostate cancer patients treated with hormonal ablation (HA), external beam radiation therapy (EBRT), and high-dose rate brachytherapy (HDR). Methods and Materials: From 1999 to 2002, 100 men who met the criteria of intermediate-risk prostate cancer were treated with neoadjuvant HA consisting of Lupron injections. After two to three months, they were started on EBRT and were treated to the prostate and seminal vesicles in daily fractions of 180 cGy to a total dose of 5040 cGy. Within four weeks of completion of EBRT, patients received three fractions of HDR, the first 26 of whom were treated with three fractions of 550 cGy each. Gradually the dose of HDR was escalated to 650 cGy. All but one patient received hormone therapy for at least one year. Intermediate risk was defined as having at least one of the following characteristics: Pretreatment PSA of at least 10 ng/ml; Gleason score of at least 7; clinical stage of at least T2b. PSA bounce was defined by Caritz et al as a postradiation PSA increase of 0.1 ng/ml or greater above the level before bounce, followed by a subsequent decrease to or below that level with PSA 0.2 ng/ml as the floor. Results: The median follow-up was 32 months with a range of 21 to 54 months. Median age of the patients evaluated was 68 years (45-76 years). The median pretreatment PSA was 11.25 ng/ml (0.02-120 ng/ml) and median Gleason score was 7. The
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median clinical stage was T2b. Using the definition as described above, 6 patients (6%) met the criteria of having PSA bounce. Median time to PSA bolunce was 20.5 months from initiation of EBRT. Conclusion: When compared with published data reporting an incidence of PSA bounce of 35% in patients treated with lowdose rate permanent radioactive seeds, patients receiving HDR temporary implants showed an incidence of 6%. Median time to PSA bolunce was similar at 18 months and 20.5 months respectively. Any increase in posttreament PSA in patients treated with high-dose rate brachytherapy must be considered significant and observed carefully. The role that hormonal ablation plays in this apparent lack of PSA bounce may be significant, but cannot be conclusively drawn from these data. 312 poster High dose rate brachytherapy as conservative treatment for vulvar cancer
M. Jolicoeur I, S. David ~, A. Devieux ~, T. V. Nguyen ~, P. Drouirf , D. Provencher~, P. GauthieP ~University of Montreal, Radio-oncology, Montreal, Canada 2University of Montreal, Gyneco-oncology, Montreal, Canada Purpose: To evaluate the safety of high dose rate (HDR) brachytherapy as sole treatment for patients vulvar carcinoma. Methods: Patients were eligible in this pilot study if they had a vulvar carcinoma stage Tis, T1 NO M0 or a recurrent carcinoma in situ. which would necessitate extensive surgery. The implants were performed according to the location of the tumor. Dosimetry was CT scan assisted with optimization allowed. An Iridium-192 afterloading system was used to deliver a total dose of 36 Gy in 12 fractions over less than 120 hours. Results: From February 1998 and August 2003, 7 patients median age 60 years were included in this prospective study. Three of which had in situ primary and four recurrent in situ carcinoma. With a median follow-up of 30 months, disease free survival and survival are respectively 98% and 100% at 3 years. Acute toxicity was a grade 2 moist desquamation in 100% of the patients. Late toxicity was found in two: one patient experiencing soft tissue necrosis successfully treated with hyperbaric oxygenotherapy and one with extensive telangiecasia.. Conclusion: Interstitial HDR brachytherapy as an exclusive treatment can be used with good results to spare extensive surgery to patients with vulvar cancer. Local control is excellent and toxicity is acceptable. 313 poster Adjuvant High Dose Rate Brachytherapy alone or combined with external beam radiation in endometrial cancer
M. Jorqe Lemos, M. Ortiz Monterrey, M.M. Sanchez Aragon, I. Monteiro Grillo Hospital de Santa Maria, Radiotherapy, Lisbon, Portugal Purpose: To evaluate the treatment results and toxicity in patients (pts) with endometrial cancer treated with postoperative intravaginal High Dose Rate brachytherapy(IV HDR BT) and external beam radiotherapy (EBRT) Material and Methods: Between April 1997 and April 2003 two hundred forty five pts, median age 65(37-93) years, with endometrial cancer, 233 (91%) adenocarcinomas (GI 110; G2 98; G3 21) and 12 sarcomas were submitted to a total abdominal hysterectomy and bilateral oophorectomy and pelvic lymphadenectomy in 88 pts. According the FIGO classification the pts were staged in (IB 113, IC 53, IIA 21, liB 11, IliA 27, IlIC
undisturbed growth (n=5) served as controls. Three animals were irradiated per time point and exposure condition. At least two flow cytometrical analyses were carried out per animal. Flow cytometry was performed after 6-diamidino-2-phenylindole (DAPI) staining of disintegrated tumor tissue fragments using a PAS II flow cytometer ( Partec, Germany (. Results: By flow cytometric analysis this tumor consisted of a mixture of diploid and aneuploid cells, with the latter cohort possessing a constant DNAqndex of 1.9 + 0.06. Only the aneuploid cell fraction which mainly represented the tumor population was used for further analysis. Comparison of sham treated (empty tube) and untreated controls did not show a differential effect of tube insertion on cell cycle regulation. Under both treatment modalities (dose 20 Gy) the fraction of aneuploid cells in G2M-phase increased significantly within 48 h (PDR, Mann-Whitney Test p<0.05) and 24 h (CLDR, MannWhitney Test p<0.05) after initiation of therapy. To avoid multiple statistical testing at the different time points the Kolmogorov-Smirnov was used as a non-parametric statistical test to compare the corresponding cell cycle phases of the two treatment arms (e.g. G1 CLDR vs. G1 PDR etc.). Differential effects on cell cycle progression were only found in the G2M fraction after irradiation with 20 Gy (p<0,05). Conclusion: Cell cycle progression represents another important factor beneath incomplete repair when comparing the radiobiological effects of different fractionation schedules. When applying higher doses PDR and CLDR brachytherapy do not effect cell cycle progression differently. These data further expand our mechanistical understanding of PDR and CLDR brachytherapy. 311 poster Prostate specific antigen bounce after hormonal ablation, external beam radiation therapy and high dose rate brachytherapy in the treatment of prostate cancer
R. Ivker ~, B. Low2, A. Helfman 3, S. Shoengolcf , A. Strumeyer ~, W. Chen e, L. Bell z INewark Beth Israel Medical Center, Department of Radiation Oncology, Newark, U.S.A. 2Newark Beth Israel, Division of Medical Oncology, Newark, U.S.A. Purpose: To determine the incidence of the phenomenon known as prostate specific antigen (PSA) bounce in prostate cancer patients treated with hormonal ablation (HA), external beam radiation therapy (EBRT), and high-dose rate brachytherapy (HDR). Methods and Materials: From 1999 to 2002, 100 men who met the criteria of intermediate-risk prostate cancer were treated with neoadjuvant HA consisting of Lupron injections. After two to three months, they were started on EBRT and were treated to the prostate and seminal vesicles in daily fractions of 180 cGy to a total dose of 5040 cGy. Within four weeks of completion of EBRT, patients received three fractions of HDR, the first 26 of whom were treated with three fractions of 550 cGy each. Gradually the dose of HDR was escalated to 650 cGy. All but one patient received hormone therapy for at least one year. Intermediate risk was defined as having at least one of the following characteristics: Pretreatment PSA of at least 10 ng/ml; Gleason score of at least 7; clinical stage of at least T2b. PSA bounce was defined by Caritz et al as a postradiation PSA increase of 0.1 ng/ml or greater above the level before bounce, followed by a subsequent decrease to or below that level with PSA 0.2 ng/ml as the floor. Results: The median follow-up was 32 months with a range of 21 to 54 months. Median age of the patients evaluated was 68 years (45-76 years). The median pretreatment PSA was 11.25 ng/ml (0.02-120 ng/ml) and median Gleason score was 7. The
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median clinical stage was T2b. Using the definition as described above, 6 patients (6%) met the criteria of having PSA bounce. Median time to PSA bolunce was 20.5 months from initiation of EBRT. Conclusion: When compared with published data reporting an incidence of PSA bounce of 35% in patients treated with lowdose rate permanent radioactive seeds, patients receiving HDR temporary implants showed an incidence of 6%. Median time to PSA bolunce was similar at 18 months and 20.5 months respectively. Any increase in posttreament PSA in patients treated with high-dose rate brachytherapy must be considered significant and observed carefully. The role that hormonal ablation plays in this apparent lack of PSA bounce may be significant, but cannot be conclusively drawn from these data. 312 poster High dose rate brachytherapy as conservative treatment for vulvar cancer
M. Jolicoeur I, S. David ~, A. Devieux ~, T. V. Nguyen ~, P. Drouirf , D. Provencher~, P. GauthieP ~University of Montreal, Radio-oncology, Montreal, Canada 2University of Montreal, Gyneco-oncology, Montreal, Canada Purpose: To evaluate the safety of high dose rate (HDR) brachytherapy as sole treatment for patients vulvar carcinoma. Methods: Patients were eligible in this pilot study if they had a vulvar carcinoma stage Tis, T1 NO M0 or a recurrent carcinoma in situ. which would necessitate extensive surgery. The implants were performed according to the location of the tumor. Dosimetry was CT scan assisted with optimization allowed. An Iridium-192 afterloading system was used to deliver a total dose of 36 Gy in 12 fractions over less than 120 hours. Results: From February 1998 and August 2003, 7 patients median age 60 years were included in this prospective study. Three of which had in situ primary and four recurrent in situ carcinoma. With a median follow-up of 30 months, disease free survival and survival are respectively 98% and 100% at 3 years. Acute toxicity was a grade 2 moist desquamation in 100% of the patients. Late toxicity was found in two: one patient experiencing soft tissue necrosis successfully treated with hyperbaric oxygenotherapy and one with extensive telangiecasia.. Conclusion: Interstitial HDR brachytherapy as an exclusive treatment can be used with good results to spare extensive surgery to patients with vulvar cancer. Local control is excellent and toxicity is acceptable. 313 poster Adjuvant High Dose Rate Brachytherapy alone or combined with external beam radiation in endometrial cancer
M. Jorqe Lemos, M. Ortiz Monterrey, M.M. Sanchez Aragon, I. Monteiro Grillo Hospital de Santa Maria, Radiotherapy, Lisbon, Portugal Purpose: To evaluate the treatment results and toxicity in patients (pts) with endometrial cancer treated with postoperative intravaginal High Dose Rate brachytherapy(IV HDR BT) and external beam radiotherapy (EBRT) Material and Methods: Between April 1997 and April 2003 two hundred forty five pts, median age 65(37-93) years, with endometrial cancer, 233 (91%) adenocarcinomas (GI 110; G2 98; G3 21) and 12 sarcomas were submitted to a total abdominal hysterectomy and bilateral oophorectomy and pelvic lymphadenectomy in 88 pts. According the FIGO classification the pts were staged in (IB 113, IC 53, IIA 21, liB 11, IliA 27, IlIC