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Treatment and Prognosis of Patients with Late Rectal Bleeding after Intensity Modulated Radiation Therapy (IMRT) for Prostate Cancer
I. J. Radiation Oncology d Biology d Physics
S346
Volume 78, Number 3, Supplement, 2010
patients (83%) had their pathology reviewed for a second opinion by the same group of pathologists. Patients were followed with PSA tests every 6 months. Kaplan-Meier estimates of PSA progression-free survival (PFS) were determined based upon a PSA nadir of 0.2 ng/ml or less. PSA progression was defined as 2 or more consecutive rises above 0.2 ng/ml. Results: The overall PSA PFS rate achieved at 10 years was 75%. One hundred six patients had a maximal tumor length to core length (TL/CL) of\=50% among needles with Gleason 4+4=8, and 34 greater than 50%. Patients with a maximum TL/CL\=50% had 80% biochemical control vs. 59% with . 50% TL/CL (p value .0098). Eighty-seven patients had sextant biopsies. Sixty-five patients had one sextant location with Gleason 4+4=8 and 22 with more than one location positive. Patients with one location positive had an 85% biochemical control at 10 years vs. 23% with more than one location positive (p value .0001). Conclusions: With modern radiation therapy utilizing I-125 brachytherapy and EBRT without androgen suppression, patients with early stage Gleason 4+4=8 achieve a high rate of biochemical control at 10 years (75%). Patients with pathologic features of Gleason Score 4+4=8 TL/CL\=50% or only one location of a sextant biopsy positive with Gleason Score 4+4=8 have improved 10-year year biochemical control of disease (80% and 85%, respectively). Author Disclosure: F.J. Schnell, None; J. Benton, None; F. Critz, None; J. Gargus, None; S. Gregory, None; C. Levitt, None; M. Merlin, None; S. Rosenbaum, None; P. Shrake, None; G. Stillwagon, None.
2319
Treatment and Prognosis of Patients with Late Rectal Bleeding after Intensity Modulated Radiation Therapy (IMRT) for Prostate Cancer
S. Takemoto, Y. Shibamoto, A. Nagai, S. Ayakawa, M. Mimura, C. Sugie, T. Yanagi, S. Otsuka, K. Kosaki, T. Murai Nagoya City University, Nagoya, Japan Purpose/Objective(s): Radiation proctitis after IMRT for prostate cancer differs from that seen after pelvic irradiation in that this adverse event is a result of high-dose radiation to the very small area in the rectum. The purpose of this study was to evaluate results of treatment for hemorrhagic proctitis after prostate IMRT. Materials/Methods: Between November 2004 and October 2009, 391 patients with prostate cancer were treated with IMRT with or without hormone therapy in two institutions. Among them, 62 patients developing late rectal bleeding were evaluated. IMRT was delivered by a linear accelerator with 5 static ports of 18-MV photons or helical tomotherapy with 6-MV photons. The planned doses were 70 to 78 Gy delivered in 35 to 39 fractions. The median age of patients was 70 years. D’Amico’s risk classification was low in 15 patients, intermediate in 16 and high in 31. The median follow-up period was 35 months. In addition to the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0, the following 4-point scale was used to evaluate the grade of bleeding and efficacy of treatment: score 3, 3 or more episodes of bleeding per week; score 2, 0.5-2 episodes per week; score 1, less than one episode in 2 weeks; and score 0, no bleeding. Amounts of bleeding were scored as follows: score 3, severe (reddened toilet bowl); score 2, moderate (blood on stool surface); score 1, mild (blood spot on paper); and score 0, no bleeding. The grade of rectal bleeding was evaluated by summing the frequency and amount scores. Steroid suppositories and/or steroid enemas were administered for pharmacotherapy. The frequency of administration was up to twice daily, depending on the severity. Endoscopic Argon plasma coagulation (APC) was performed at an argon flow rate of 1.0 L/min with a voltage of 40 W. Results: CTCAE grade of bleeding was 1 in 33 patients, 2 in 21, and 3 in 7. Rectal bleeding occurred at 3-41 months after IMRT (median, 13 months). Eighteen of 50 patients (36%) observed without treatment showed improvement (median bleeding score improving from 2.8 to 2.2) and bleeding stopped in 16 (32%). Seventeen of 27 patients (63%) administered steroid suppositories and/ or enemas showed improvement (median bleeding score, from 4.0 to 2.1) and bleeding stopped in 4 (15%). Improvement was observed in 1 to 30 months (median, 5 months). All of 6 patients treated with APC showed improvement within 2 months (median score, from 4.7 to 2.0) and bleeding stopped in 2 patients. Conclusions: To manage rectal bleeding not disappearing after adequate periods of observation, steroid suppositories and enemas are expected to be effective in more than half of patients. Even when patients have no response to pharmacotherapy, APC is effective and stops or decreases bleeding in a relatively short period. Author Disclosure: S. Takemoto, None; Y. Shibamoto, None; A. Nagai, None; S. Ayakawa, None; M. Mimura, None; C. Sugie, None; T. Yanagi, None; S. Otsuka, None; K. Kosaki, None; T. Murai, None.
2320
Comparing Long-term Biochemical Control of Prostate Cancer after Standard or Hyperfractionated Radiation Therapy: Evidence of a Different Behavior between Low-intermediate and High Risk Patients
R. Valdagni1, A. E. Nahum2, T. Rancati1, M. Tiziana1, P. Montanaro3, C. Italia4, A. Lanceni5, B. Avuzzi1, C. Fiorino6 1
Fondazione IRCCS - Istituto Nazionale Tumori, Milan, Italy, 2Clatterbridge Centre for Oncology, Wirral, United Kingdom, Casa di Cura Pio X, Milan, Italy, 4Ospedale Riuniti di Bergamo, Bergamo, Italy, 5Azienda Ospedaliera di Busto Arsizio, Busto Arsizio, Italy, 6Scientific Institute San Raffaele, Milan, Italy 3
Purpose/Objective(s): To report the long-term biochemical relapse free survival (bRFS) of a non-randomized trial comparing standard (SFX, 2.0Gy/day) and hyperfractionated (HFX, 1.2Gy twice daily) schedules and to analyze the implications for the alpha/beta (a/b) of prostate carcinoma (PCa). Materials/Methods: Between 1993 and 2003, 370 pts entered the study. Three hundred thirty pts are evaluable for this analysis (179 SFX, 151 HFX). Pre-treatment and treatment variables were similar in the two groups (Valdagni et al., Radiother Oncol 2005). Median doses were 79.2Gy and 74Gy for HFX and SFX pts, respectively; median follow-up is 7.5yrs. The two regimens were compared in terms of 5yr and 7.5yr bRFS by uni- (log-rank test) and multivariate analyses (Cox regression). Based on published relationships between EQD2 and 5yr bRFS (Diez et al. and Viani et al., IJROBP 2009), a/b values can be estimated. Results: 7.5yr bRFS were 53.4% (+/-4.4%, 95% CI) and 65.4% (+/-4.0%) for HFX and SFX, respectively (p = 0.13). HFX was associated with a poorer outcome in NCCN low+intermediate (LIR) pts (7.5yr bRFS: 56.6% vs. 73.5%, p = 0.048) while no difference was seen for high-risk pts (HR) (bRFS: 44.1% vs. 45.3%). Multivariate analysis revealed that NCCN risk groupings (HR vs. LIR: OR = 0.59, p = 0.009) and age (\ vs. $70yrs; OR = 0.67, p = 0.03) were the main predictors of worse bRFS. In the
S346
Volume 78, Number 3, Supplement, 2010
patients (83%) had their pathology reviewed for a second opinion by the same group of pathologists. Patients were followed with PSA tests every 6 months. Kaplan-Meier estimates of PSA progression-free survival (PFS) were determined based upon a PSA nadir of 0.2 ng/ml or less. PSA progression was defined as 2 or more consecutive rises above 0.2 ng/ml. Results: The overall PSA PFS rate achieved at 10 years was 75%. One hundred six patients had a maximal tumor length to core length (TL/CL) of\=50% among needles with Gleason 4+4=8, and 34 greater than 50%. Patients with a maximum TL/CL\=50% had 80% biochemical control vs. 59% with . 50% TL/CL (p value .0098). Eighty-seven patients had sextant biopsies. Sixty-five patients had one sextant location with Gleason 4+4=8 and 22 with more than one location positive. Patients with one location positive had an 85% biochemical control at 10 years vs. 23% with more than one location positive (p value .0001). Conclusions: With modern radiation therapy utilizing I-125 brachytherapy and EBRT without androgen suppression, patients with early stage Gleason 4+4=8 achieve a high rate of biochemical control at 10 years (75%). Patients with pathologic features of Gleason Score 4+4=8 TL/CL\=50% or only one location of a sextant biopsy positive with Gleason Score 4+4=8 have improved 10-year year biochemical control of disease (80% and 85%, respectively). Author Disclosure: F.J. Schnell, None; J. Benton, None; F. Critz, None; J. Gargus, None; S. Gregory, None; C. Levitt, None; M. Merlin, None; S. Rosenbaum, None; P. Shrake, None; G. Stillwagon, None.
2319
Treatment and Prognosis of Patients with Late Rectal Bleeding after Intensity Modulated Radiation Therapy (IMRT) for Prostate Cancer
S. Takemoto, Y. Shibamoto, A. Nagai, S. Ayakawa, M. Mimura, C. Sugie, T. Yanagi, S. Otsuka, K. Kosaki, T. Murai Nagoya City University, Nagoya, Japan Purpose/Objective(s): Radiation proctitis after IMRT for prostate cancer differs from that seen after pelvic irradiation in that this adverse event is a result of high-dose radiation to the very small area in the rectum. The purpose of this study was to evaluate results of treatment for hemorrhagic proctitis after prostate IMRT. Materials/Methods: Between November 2004 and October 2009, 391 patients with prostate cancer were treated with IMRT with or without hormone therapy in two institutions. Among them, 62 patients developing late rectal bleeding were evaluated. IMRT was delivered by a linear accelerator with 5 static ports of 18-MV photons or helical tomotherapy with 6-MV photons. The planned doses were 70 to 78 Gy delivered in 35 to 39 fractions. The median age of patients was 70 years. D’Amico’s risk classification was low in 15 patients, intermediate in 16 and high in 31. The median follow-up period was 35 months. In addition to the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0, the following 4-point scale was used to evaluate the grade of bleeding and efficacy of treatment: score 3, 3 or more episodes of bleeding per week; score 2, 0.5-2 episodes per week; score 1, less than one episode in 2 weeks; and score 0, no bleeding. Amounts of bleeding were scored as follows: score 3, severe (reddened toilet bowl); score 2, moderate (blood on stool surface); score 1, mild (blood spot on paper); and score 0, no bleeding. The grade of rectal bleeding was evaluated by summing the frequency and amount scores. Steroid suppositories and/or steroid enemas were administered for pharmacotherapy. The frequency of administration was up to twice daily, depending on the severity. Endoscopic Argon plasma coagulation (APC) was performed at an argon flow rate of 1.0 L/min with a voltage of 40 W. Results: CTCAE grade of bleeding was 1 in 33 patients, 2 in 21, and 3 in 7. Rectal bleeding occurred at 3-41 months after IMRT (median, 13 months). Eighteen of 50 patients (36%) observed without treatment showed improvement (median bleeding score improving from 2.8 to 2.2) and bleeding stopped in 16 (32%). Seventeen of 27 patients (63%) administered steroid suppositories and/ or enemas showed improvement (median bleeding score, from 4.0 to 2.1) and bleeding stopped in 4 (15%). Improvement was observed in 1 to 30 months (median, 5 months). All of 6 patients treated with APC showed improvement within 2 months (median score, from 4.7 to 2.0) and bleeding stopped in 2 patients. Conclusions: To manage rectal bleeding not disappearing after adequate periods of observation, steroid suppositories and enemas are expected to be effective in more than half of patients. Even when patients have no response to pharmacotherapy, APC is effective and stops or decreases bleeding in a relatively short period. Author Disclosure: S. Takemoto, None; Y. Shibamoto, None; A. Nagai, None; S. Ayakawa, None; M. Mimura, None; C. Sugie, None; T. Yanagi, None; S. Otsuka, None; K. Kosaki, None; T. Murai, None.
2320
Comparing Long-term Biochemical Control of Prostate Cancer after Standard or Hyperfractionated Radiation Therapy: Evidence of a Different Behavior between Low-intermediate and High Risk Patients
R. Valdagni1, A. E. Nahum2, T. Rancati1, M. Tiziana1, P. Montanaro3, C. Italia4, A. Lanceni5, B. Avuzzi1, C. Fiorino6 1
Fondazione IRCCS - Istituto Nazionale Tumori, Milan, Italy, 2Clatterbridge Centre for Oncology, Wirral, United Kingdom, Casa di Cura Pio X, Milan, Italy, 4Ospedale Riuniti di Bergamo, Bergamo, Italy, 5Azienda Ospedaliera di Busto Arsizio, Busto Arsizio, Italy, 6Scientific Institute San Raffaele, Milan, Italy 3
Purpose/Objective(s): To report the long-term biochemical relapse free survival (bRFS) of a non-randomized trial comparing standard (SFX, 2.0Gy/day) and hyperfractionated (HFX, 1.2Gy twice daily) schedules and to analyze the implications for the alpha/beta (a/b) of prostate carcinoma (PCa). Materials/Methods: Between 1993 and 2003, 370 pts entered the study. Three hundred thirty pts are evaluable for this analysis (179 SFX, 151 HFX). Pre-treatment and treatment variables were similar in the two groups (Valdagni et al., Radiother Oncol 2005). Median doses were 79.2Gy and 74Gy for HFX and SFX pts, respectively; median follow-up is 7.5yrs. The two regimens were compared in terms of 5yr and 7.5yr bRFS by uni- (log-rank test) and multivariate analyses (Cox regression). Based on published relationships between EQD2 and 5yr bRFS (Diez et al. and Viani et al., IJROBP 2009), a/b values can be estimated. Results: 7.5yr bRFS were 53.4% (+/-4.4%, 95% CI) and 65.4% (+/-4.0%) for HFX and SFX, respectively (p = 0.13). HFX was associated with a poorer outcome in NCCN low+intermediate (LIR) pts (7.5yr bRFS: 56.6% vs. 73.5%, p = 0.048) while no difference was seen for high-risk pts (HR) (bRFS: 44.1% vs. 45.3%). Multivariate analysis revealed that NCCN risk groupings (HR vs. LIR: OR = 0.59, p = 0.009) and age (\ vs. $70yrs; OR = 0.67, p = 0.03) were the main predictors of worse bRFS. In the