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Proceedings of the 40th Annual ASTRO Meeting 1017 A STUDY OF THE EFFECTS OF INTERNAL ORGAN MOTION AND SETUP ERROR ON DOSE ESCALATION IN CONFORMAL PROSTATE TREATMENTS L. Happersett, D. Crean, S. Bull, O. Lyass, G. Mageras, M. Zelefsky, C. Burman, S.Leibel,C. Chui, Z. Fuks, M. van Herk#, H. Kooy*, C. Ling, R. Mohant*, G. Kutchertt* Memorial Sloan Kettering Cancer Center, NY, *Joint Center for Radiation Therapy, Boston, tNetherlands Cancer Institute, Amsterdam, ttMedical College of Virginia, Richmond, tt~Universitaire Ziekenhuizen, Leuven Purpose: Clinical dose escalation trials for prostate cancer have prompted the development of conformal treatment techniques with tighter dose distributions which aim to increase the prostate dose without increasing the dose to surrounding normal structures. This study compares the effect of internal organ motion and patient setup error on dose delivered to target and non-target organs for three such treatment techniques. Materials and Methods: We examined 3 types of treatments performed at this center: (1) 6 transaxial shaped fields, with a prescribed dose of 75.6 Gy to the planning target volume (PTV); (2) the same 6 fields treated to 72 Gy followed by boost to 81 Gy, with the rectum blocked in the boost fields; (3) 81Gy intensity modulated treatment, using 5 transaxial fields, with a dose gradient (from 76 to 81Gy) in the region of overlap of the PTV and rectum. The clinical target volume (CTV) consisted of the prostate plus the seminal vesicles, while the PTV enclosed the CTV with margins of 0.6 cm posteriorly, and 1 cm elsewhere. The effects of organ motion were examined by designing the treatment on the patient's planning CT scan, then applying the plan to 3 subsequent scans taken over the treatment course, (referred to as treatment scans), which were registered to the planning scan using the pelvic bones, Setup errors were assumed to be random with a 3 mm standard deviation(SD) in the 3 possible directions and were simulated by means of convolution in the dose calculation. Results: Analysis of the first 10 patients are summarized in the Table, which shows the Prostate Rectal Wall mean and 1SD values for tumor control probability (TCP) for the prostate, percent Type TCP (%) V81 p (%) V75Rw (%) volume of the prostate receiving 81Gy(V8 lp) and percent volume of the rectal wall Plan Txt Plan Txt Plan Txt receiving 75Gy (V75Rw). Plans 2 and 3 on average exhibit higher TCP and V81p values 1 81_+1 81+1 4_+6 3+_4 23_+4 15__+7 than plan 1, for both the planning scan (without organ motion or setup error) and the treatment scans (Txt in table). In addition, plan 3 delivers the prescribed dose to a larger 2 892-_2 88+4 90-+10 86+14 12-+5 lOL-_6 fraction of the prostate than plan 2, due to higher dose conformality. However, the ISD 3 90-+1 87_+3 97_+2 91+7 10!-_l 10-+6 values are greater for plans 2 and 3 than plan 1 which show an increased susceptibility of some of these plans to motion and setup error. Examination of dose distributions revealed that 4 patients had prostate displacements either posteriorly or superiorly from the planned position, which was sufficient to affect the prostate dose in plans 2 and 3. Although patient-to-patient variations in treatment V75Rw were significant (ISD = 6%), the average treatment V75RW for the group of patients was 5% lower for plans 2 and 3 than for plan 1. Results on a larger group of patients, as well as for the seminal vesicles and bladder wall, will also be presented. Conclusion: The 3D conformal approach presented here allows for a safe escalation of dose, however the amount of escalation for a fraction of patients is partially reduced when prostate motion and setup error are taken into account. This is due partly to the tighter rectal constraints. Variation in rectal dose due to treatment uncertainties implies that using the planning scan alone in determining dose may not be a reliable indicator of actual rectal dose received. 217 1018 RECTAL BLEEDING AFTER CONFORMAL RADIOTHERAPY OF PROSTATE CANCER AND DOSE VOLUME HISTOGRAMS A. Jackson, PhD, M. Zelefsky, MD, D. Cowan ~, MD, E. Venkatraman, PhD, M. Skwarehuk, PhD, C. Burman, PhD, G. Kutcher, PhD, Z. Fuks, MD, S. Leibel, MD, and C.C. Ling, PhD Memorial Sloan-Kettering Cancer Center, New York, NY 10021, ~Institut Paoli-Calmettes Cancer Center, 13009 Marseilte, France Purpose/Objective: In patients treated for prostate cancer with (3DCRT), the frequency of rectal bleeding increases as the prescription dose rises above 70 Gy. The purpose of this study is determine the impact of volume of rectal wall exposed to high doses on the incidence of rectal bleeding by identifying features of the dose volume histogram for the rectal wall that correlate with this endpoint after 3DCRT of prostate cancer. Materials and Methods: 251 and 270 patients with Tle-T3 prostate cancer were previously treated with 3DCRT with minimum target doses of 70.2 and 75.6 Gy respectively, and followed for at least 18 months. All patients in the current analysis were treated using a co-planar 6- field technique (2 lateral and 4 oblique fields). Patients with rectal bleeding within 18 months after treatment were classified as non- bleeders (grade 0) or bleeders (grades 2 and 3), using the RTOG morbidity scale. Rectal bleeding was observed in 15/251 (6%) of the patients (14 Grade 2, 1 Grade 3) treated at 70.2 Gy and 32/270 (12 %) of the patients (30 grade 2, 2 grade 3) treated at 75.6 Gy. Treatment plans were analyzed for 34 non-bleeders and 12 bleeders receiving 70.2 Gy, and 63 non-bleeders and 23 bleeders receiving 75.6 Gy. Dose Volume Histograms (DVHs) for the anatomic rectal wall were generated. Multivariate analyses were performed in both dose groups to investigate possible correlations of rectal bleeding with the rectal wall volume (rwv), and the absolute and percent volumes receiving 50, 75 and 95 % of the prescription dose (v50, v75, v95, %v50, %v75, %v95). Average DVHs of the bleeders and non-bleeders were generated and a permutation test (constructed from a Monte-Carlo simulation) was used to assess the significance of the difference between them in each dose group. Results: The most significant single variables associated with rectal bleeding for patients receiving 70.2 Gy and 75.6 Gy were %v50 and rwv respectively. In the presence of %v50, rwv and %v75 were both significant for patients receiving 70.2 Gy. In the presence of rwv, %v50 and %v75 were also independently significant for patients receiving 75.6 Gy. Consistent with these results, the mean percent volume DVHs for the bleeders were found to be significantly higher than those of the non-bleeders for both dose groups, while mean absolute volume DVHs were similar at doses above 45 Gy. Results from a larger number of patients will be presented, and the differences between DVHs of bleeders and non-bleeders with similar rectal wall volumes will be illustrated. Conclusion: Small rectal wall volume increased the risk of rectal bleeding for patients treated with 3DCRT for prostate cancer to doses in excess of 70 Gy. In both dose groups, these small rectal wall volumes were reflected in the higher values of percent volume exposed to a given dose occurring in the mean DVH of patients with rectal bleeding. The significance of %v50 and %v75 in the presence ofrwv implies that further correlations exist between rectal bleeding and percent volume DVHs in patients with similar rectal wall volumes. This work was supported in part by N.C.I./N.I.H. 2P01-CA-59017.

Rectal bleeding after conformal radiotherapy of prostate cancer and dose volume histograms

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Proceed ings o f the 4 0 t h A n n u a l A S T R O Meet ing

1017 A STUDY OF THE EFFECTS OF INTERNAL ORGAN MOTION AND SETUP ERROR ON DOSE ESCALATION IN CONFORMAL PROSTATE TREATMENTS

L. Happersett, D. Crean, S. Bull, O. Lyass, G. Mageras, M. Zelefsky, C. Burman, S.Leibel,C. Chui, Z. Fuks, M. van Herk #, H. Kooy*, C. Ling, R. Mohant*, G. Kutcher tt*

Memorial Sloan Kettering Cancer Center, NY, *Joint Center for Radiation Therapy, Boston, tNetherlands Cancer Institute, Amsterdam, ttMedical College of Virginia, Richmond, tt~Universitaire Ziekenhuizen, Leuven

Purpose: Clinical dose escalation trials for prostate cancer have prompted the development of conformal treatment techniques with tighter dose distributions which aim to increase the prostate dose without increasing the dose to surrounding normal structures. This study compares the effect of internal organ motion and patient setup error on dose delivered to target and non-target organs for three such treatment techniques.

Materials and Methods: We examined 3 types of treatments performed at this center: (1) 6 transaxial shaped fields, with a prescribed dose of 75.6 Gy to the planning target volume (PTV); (2) the same 6 fields treated to 72 Gy followed by boost to 81 Gy, with the rectum blocked in the boost fields; (3) 81Gy intensity modulated treatment, using 5 transaxial fields, with a dose gradient (from 76 to 81Gy) in the region of overlap of the PTV and rectum. The clinical target volume (CTV) consisted of the prostate plus the seminal vesicles, while the PTV enclosed the CTV with margins of 0.6 cm posteriorly, and 1 cm elsewhere. The effects of organ motion were examined by designing the treatment on the patient's planning CT scan, then applying the plan to 3 subsequent scans taken over the treatment course, (referred to as treatment scans), which were registered to the planning scan using the pelvic bones, Setup errors were assumed to be random with a 3 mm standard deviation(SD) in the 3 possible directions and were simulated by means of convolution in the dose calculation.

Results: Analysis of the first 10 patients are summarized in the Table, which shows the Prostate Rectal Wall mean and 1SD values for tumor control probability (TCP) for the prostate, percent Type TCP (%) V81 p (%) V75Rw (%) volume of the prostate receiving 81Gy(V8 lp) and percent volume of the rectal wall Plan Txt Plan Txt Plan Txt receiving 75Gy (V75Rw). Plans 2 and 3 on average exhibit higher TCP and V81p values 1 81_+1 81+1 4_+6 3+_4 23_+4 15__+7 than plan 1, for both the planning scan (without organ motion or setup error) and the treatment scans (Txt in table). In addition, plan 3 delivers the prescribed dose to a larger 2 892-_2 88+4 90-+10 86+14 12-+5 lOL-_6 fraction of the prostate than plan 2, due to higher dose conformality. However, the ISD 3 90-+1 87_+3 97_+2 91+7 10!-_l 10-+6 values are greater for plans 2 and 3 than plan 1 which show an increased susceptibility of some of these plans to motion and setup error. Examination of dose distributions revealed that 4 patients had prostate displacements either posteriorly or superiorly from the planned position, which was sufficient to affect the prostate dose in plans 2 and 3. Although patient-to-patient variations in treatment V75Rw were significant (ISD = 6%), the average treatment V75RW for the group of patients was 5% lower for plans 2 and 3 than for plan 1. Results on a larger group of patients, as well as for the seminal vesicles and bladder wall, will also be presented.

Conclusion: The 3D conformal approach presented here allows for a safe escalation of dose, however the amount of escalation for a fraction of patients is partially reduced when prostate motion and setup error are taken into account. This is due partly to the tighter rectal constraints. Variation in rectal dose due to treatment uncertainties implies that using the planning scan alone in determining dose may not be a reliable indicator of actual rectal dose received.

217

1018 RECTAL BLEEDING AFTER CONFORMAL RADIOTHERAPY OF PROSTATE CANCER AND DOSE VOLUME HISTOGRAMS

A. Jackson, PhD, M. Zelefsky, MD, D. Cowan ~, MD, E. Venkatraman, PhD, M. Skwarehuk, PhD, C. Burman, PhD, G. Kutcher, PhD, Z. Fuks, MD, S. Leibel, MD, and C.C. Ling, PhD

Memorial Sloan-Kettering Cancer Center, New York, NY 10021, ~Institut Paoli-Calmettes Cancer Center, 13009 Marseilte, France

Purpose/Objective: In patients treated for prostate cancer with (3DCRT), the frequency of rectal bleeding increases as the prescription dose rises above 70 Gy. The purpose of this study is determine the impact of volume of rectal wall exposed to high doses on the incidence of rectal bleeding by identifying features of the dose volume histogram for the rectal wall that correlate with this endpoint after 3DCRT of prostate cancer.

Materials and Methods: 251 and 270 patients with Tle-T3 prostate cancer were previously treated with 3DCRT with minimum target doses o f 70.2 and 75.6 Gy respectively, and followed for at least 18 months. All patients in the current analysis were treated using a co-planar 6- field technique (2 lateral and 4 oblique fields). Patients with rectal bleeding within 18 months after treatment were classified as non- bleeders (grade 0) or bleeders (grades 2 and 3), using the RTOG morbidity scale. Rectal bleeding was observed in 15/251 (6%) o f the patients (14 Grade 2, 1 Grade 3) treated at 70.2 Gy and 32/270 (12 %) of the patients (30 grade 2, 2 grade 3) treated at 75.6 Gy. Treatment plans were analyzed for 34 non-bleeders and 12 bleeders receiving 70.2 Gy, and 63 non-bleeders and 23 bleeders receiving 75.6 Gy. Dose Volume Histograms (DVHs) for the anatomic rectal wall were generated. Multivariate analyses were performed in both dose groups to investigate possible correlations of rectal bleeding with the rectal wall volume (rwv), and the absolute and percent volumes receiving 50, 75 and 95 % of the prescription dose (v50, v75, v95, %v50, %v75, %v95). Average DVHs of the bleeders and non-bleeders were generated and a permutation test (constructed from a Monte-Carlo simulation) was used to assess the significance of the difference between them in each dose group.

Results: The most significant single variables associated with rectal bleeding for patients receiving 70.2 Gy and 75.6 Gy were %v50 and rwv respectively. In the presence of %v50, rwv and %v75 were both significant for patients receiving 70.2 Gy. In the presence of rwv, %v50 and %v75 were also independently significant for patients receiving 75.6 Gy. Consistent with these results, the mean percent volume DVHs for the bleeders were found to be significantly higher than those of the non-bleeders for both dose groups, while mean absolute volume DVHs were similar at doses above 45 Gy. Results from a larger number of patients will be presented, and the differences between DVHs of bleeders and non-bleeders with similar rectal wall volumes will be illustrated.

Conclusion: Small rectal wall volume increased the risk of rectal bleeding for patients treated with 3DCRT for prostate cancer to doses in excess of 70 Gy. In both dose groups, these small rectal wall volumes were reflected in the higher values of percent volume exposed to a given dose occurring in the mean DVH of patients with rectal bleeding. The significance of %v50 and %v75 in the presence o f rwv implies that further correlations exist between rectal bleeding and percent volume DVHs in patients with similar rectal wall volumes.

This work was supported in part by N.C.I./N.I.H. 2P01-CA-59017.