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Organ Preservation for Muscle-Invasive Squamous Cell Carcinoma of the Urinary Bladder in the United States
E266
International Journal of Radiation Oncology Biology Physics
a contraindication for LDR brachytherapy in cases where implant is technically feasible. However, the risk of subsequent urinary retention is increased. Author Disclosure: S.J. Spencer: None. M. Chao: None. M. Guerrieri: None. W. Ding: None. M. Goharian: None. H. Ho: None. M. Ng: None. D. Healey: None. A. Tan: None. C.W. Cham: None. D. Bolton: None. N. Lawrentschuk: None. S. Sengupta: None. Y. Chan: None. A. Troy: None.
Author Disclosure: W.A. Stokes: None. E.R. Kessler: None. S. Wilson: None. E.T. Lam: None. T.W. Flaig: None. B.D. Kavanagh: Research Grant; Janssen Research & Development. T.J. Pugh: None.
2635 Organ Preservation for Muscle-Invasive Squamous Cell Carcinoma of the Urinary Bladder in the United States W.A. Stokes,1 E.R. Kessler,2 S. Wilson,3 E.T. Lam,2 T.W. Flaig,2 B.D. Kavanagh,1 and T.J. Pugh1; 1Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 2Division of Urologic Oncology, University of Colorado Denver, Aurora, CO, 3Division of Urology, University of Colorado Denver, Aurora, CO Purpose/Objective(s): Organ preservation (maximum TURBT followed by concurrent chemoradiation) is an established alternative to radical cystectomy with pelvic lymph node dissection for patients with muscle invasive bladder cancer (MIBC) who decline or are medically unfit for radical surgery. While squamous cell carcinoma (SCC) is represented in many of the studies defining organ preservation, some providers may be reluctant to offer this approach to MIBC patients with this rare histology due to its perceived poor response to therapy and adverse outcomes in comparison to more common histologies of MIBC. We therefore sought to define utilization and overall survival (OS) for patients with MIBC-SCC treated with chemo-radiation using the National Cancer Database (NCDB). Materials/Methods: We queried NCDB for patients with T2-T4 or TX, N0M0 SCC of the urinary bladder diagnosed from 2004-2012 receiving both chemotherapy and high-dose radiotherapy (55Gy) without up-front cystectomy. Patients with urothelial cell carcinoma (UCC) were queried separately to serve as a referent group for comparison. The Kaplan-Meier method estimated OS. Cox regression analysis was used to define OS associations with known variables. Results: Fifty-four SCC and 2,054 UCC patients were identified. SCC patients were more likely to be younger, female, non-white, and to have more advanced disease at presentation. Age >70, Charlson-Deyo comorbidity score >0, and stage T3 were associated with worse OS while gender, race, insurance status, household income, facility type, chemotherapy (single vs. multi-agent), and histology showed no association with OS. OS estimates were not significantly worse for SCC compared to UCC (5-year OS 25.4% vs 33.3%; adjusted hazard ratio 1.34 (95%CI 0.93-1.92); pZ0.12). Conclusion: OS did not significantly differ between SCC and UCC patients undergoing organ preservation for MIBC, while other prognostic factors were relevant in both groups. Limited prevalence and rare utilization of organ preservation may have influenced these results. Further work is needed to define the optimal therapeutic strategy for MIBC-SCC in Western countries.
Cox Regression for Mortality*
Comorbidity (v 0) 1 2+ Income Quartile (v Q1) Q2 Q3 Q4
Facility Type (v community) comprehensive community academic other T-stage (v T2) T3 T4 TX
Chemotherapy (v 1 agent) multi-agent Histology (v UCC) SCC *
Deformable Dose Accumulation to Assess Rectal Sparing Associated With Adaptive Radiation Therapy for Bladder Cancer A. Sundaramurthy,1,2 V.C. Kong,1 J. Helou,1,2 T. Rosewall,1,2 T. Craig,1,3 R.G. Bristow,1,2 A. Berlin,1,2 and P. Chung1,2; 1Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada, 2 Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 3University of Toronto, Toronto, ON, Canada Purpose/Objective(s): Adaptive strategies in bladder cancer radiotherapy allow excellent target coverage but may be associated with differences in rectal sparing. We examined 3 adaptive radiotherapy techniques using deformable image registration and dose accumulation. Materials/Methods: Fifteen patients who had radiotherapy for muscle invasive bladder cancer (simulated and treated with comfortably full bladder and empty rectum) were identified. RayStation 4.7 was used for planning, image registration and dose accumulation. New treatment plans to a dose of 55Gy in 20 fractions were created using 7-field IMRT. CTV (whole bladder) and rectum were outlined on planning CT (PCT) and 20 daily cone beam CTs (CBCT). PTVs derived from 3 adaptive strategies were compared (geometric expansions in all directions unless otherwise stated): 1. Patient specific (PS-PTV): Union of CTV from PCT and first 5 CBCT formed an “occupancy volume” (OV). PS-PTV Z 0.3 cm + OV 2. Multi-image plan of day (MI-POD): 3 library plans were created; Small (2 smallest of CTV from PCT and first 5 CBCT used to create OV. PTV Z OV + 3 mm), Medium (same as PS-PTV) and Large (1.5 cm + CTV from PCT) 3. Single image plan of day (SI-POD): Plan library created using PCT alone. Small (1.5 cm to CTV in all directions except -1.0 cm superiorly), Medium (1.5 cm in all directions except -0.5 cm superiorly) and Large (1.5 cm in all directions except 0 cm superiorly) Standard PTV (1.5 cm + CTV from PCT) was used for dose accumulation for first 5 fractions in PS-PTV & MI-POD. PTV in each strategy that fully contained the bladder on registered CBCT/fraction was recorded. Daily CBCTs were registered using deformable image registration with PCT; dose was computed on each CBCT and deformably accumulated on PCT. The PTV, CTV D99 and rectum D30 for each strategy were compared using Wilcoxon Signed Rank test or paired Student’s t test (where appropriate) with a 2-tailed p0.05 considered statistically significant. Results: Median PTV for each strategy was: SI-POD 480.9 cc, PS-PTV 391.8 cc and MI-POD 451.8. CTV D99 and median of difference in the PTV are shown below: Abstract 2636
Abstract 2635
Age (v 70) 71-80 >80
2636
Strategy
HR
95%CI
p
1.27 1.69 1.21 1.71 1.08 0.86 0.91 1.02 0.96 1.06 1.30 1.91 0.91 0.99 1.34
1.08-1.50 1.43-1.99 1.06-1.40 1.42-2.06 0.90-1.31 0.71-1.04 0.76-1.10 0.86-1.21 0.79-1.17 0.81-1.39 1.09-1.56 1.59-2.30 0.65-1.28 0.88-1.12 0.93-1.92
<0.01 <0.01 0.01 <0.01 0.41 0.12 0.34 0.84 0.69 0.66 <0.01 <0.01 0.60 0.89 0.12
adjusted for race, gender, and insurance.
Mean CTV D99 in Gy with 95% CI p values compared to SI-POD
Median of difference in the PTVcc compared to SI-POD [IQR]
SI-POD 52.9 [95% CI 52.2 e 53.7] PS-PTV 53.0 [95% CI 52.2 e 53.7, pZ0.88] 113 [82.5 e 145.7, p<0.001] MI-POD 53.0 [95% CI 52.3 e 53.7, pZ0.61] 76.5 [50.3 e 110.2, p<0.001]
Median rectum D30 was: SI-POD 36.7 Gy, PS-PTV 26.2 Gy and MIPOD 26.8 Gy. Rectal sparing was significantly better with PS-PTV and MI-POD compared to SI-POD; median of difference in rectum D30 compared to SI-POD was: PS-PTV 5Gy [pZ0.002] and MI-POD 5.3 Gy [pZ0.001] with no difference in median between PS-PTV and MI-POD, 0Gy [pZ0.509]. Conclusion: Our study demonstrated that a PTV based on multiple images (PS-PTV and MI-POD) provided superior rectal sparing while maintaining adequate target dose compared to single image strategy (SI-POD). However as MI-POD is relatively resource intensive, PS-PTV may be a preferred adaptive strategy for bladder cancer radiotherapy.
International Journal of Radiation Oncology Biology Physics
a contraindication for LDR brachytherapy in cases where implant is technically feasible. However, the risk of subsequent urinary retention is increased. Author Disclosure: S.J. Spencer: None. M. Chao: None. M. Guerrieri: None. W. Ding: None. M. Goharian: None. H. Ho: None. M. Ng: None. D. Healey: None. A. Tan: None. C.W. Cham: None. D. Bolton: None. N. Lawrentschuk: None. S. Sengupta: None. Y. Chan: None. A. Troy: None.
Author Disclosure: W.A. Stokes: None. E.R. Kessler: None. S. Wilson: None. E.T. Lam: None. T.W. Flaig: None. B.D. Kavanagh: Research Grant; Janssen Research & Development. T.J. Pugh: None.
2635 Organ Preservation for Muscle-Invasive Squamous Cell Carcinoma of the Urinary Bladder in the United States W.A. Stokes,1 E.R. Kessler,2 S. Wilson,3 E.T. Lam,2 T.W. Flaig,2 B.D. Kavanagh,1 and T.J. Pugh1; 1Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 2Division of Urologic Oncology, University of Colorado Denver, Aurora, CO, 3Division of Urology, University of Colorado Denver, Aurora, CO Purpose/Objective(s): Organ preservation (maximum TURBT followed by concurrent chemoradiation) is an established alternative to radical cystectomy with pelvic lymph node dissection for patients with muscle invasive bladder cancer (MIBC) who decline or are medically unfit for radical surgery. While squamous cell carcinoma (SCC) is represented in many of the studies defining organ preservation, some providers may be reluctant to offer this approach to MIBC patients with this rare histology due to its perceived poor response to therapy and adverse outcomes in comparison to more common histologies of MIBC. We therefore sought to define utilization and overall survival (OS) for patients with MIBC-SCC treated with chemo-radiation using the National Cancer Database (NCDB). Materials/Methods: We queried NCDB for patients with T2-T4 or TX, N0M0 SCC of the urinary bladder diagnosed from 2004-2012 receiving both chemotherapy and high-dose radiotherapy (55Gy) without up-front cystectomy. Patients with urothelial cell carcinoma (UCC) were queried separately to serve as a referent group for comparison. The Kaplan-Meier method estimated OS. Cox regression analysis was used to define OS associations with known variables. Results: Fifty-four SCC and 2,054 UCC patients were identified. SCC patients were more likely to be younger, female, non-white, and to have more advanced disease at presentation. Age >70, Charlson-Deyo comorbidity score >0, and stage T3 were associated with worse OS while gender, race, insurance status, household income, facility type, chemotherapy (single vs. multi-agent), and histology showed no association with OS. OS estimates were not significantly worse for SCC compared to UCC (5-year OS 25.4% vs 33.3%; adjusted hazard ratio 1.34 (95%CI 0.93-1.92); pZ0.12). Conclusion: OS did not significantly differ between SCC and UCC patients undergoing organ preservation for MIBC, while other prognostic factors were relevant in both groups. Limited prevalence and rare utilization of organ preservation may have influenced these results. Further work is needed to define the optimal therapeutic strategy for MIBC-SCC in Western countries.
Cox Regression for Mortality*
Comorbidity (v 0) 1 2+ Income Quartile (v Q1) Q2 Q3 Q4
Facility Type (v community) comprehensive community academic other T-stage (v T2) T3 T4 TX
Chemotherapy (v 1 agent) multi-agent Histology (v UCC) SCC *
Deformable Dose Accumulation to Assess Rectal Sparing Associated With Adaptive Radiation Therapy for Bladder Cancer A. Sundaramurthy,1,2 V.C. Kong,1 J. Helou,1,2 T. Rosewall,1,2 T. Craig,1,3 R.G. Bristow,1,2 A. Berlin,1,2 and P. Chung1,2; 1Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada, 2 Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 3University of Toronto, Toronto, ON, Canada Purpose/Objective(s): Adaptive strategies in bladder cancer radiotherapy allow excellent target coverage but may be associated with differences in rectal sparing. We examined 3 adaptive radiotherapy techniques using deformable image registration and dose accumulation. Materials/Methods: Fifteen patients who had radiotherapy for muscle invasive bladder cancer (simulated and treated with comfortably full bladder and empty rectum) were identified. RayStation 4.7 was used for planning, image registration and dose accumulation. New treatment plans to a dose of 55Gy in 20 fractions were created using 7-field IMRT. CTV (whole bladder) and rectum were outlined on planning CT (PCT) and 20 daily cone beam CTs (CBCT). PTVs derived from 3 adaptive strategies were compared (geometric expansions in all directions unless otherwise stated): 1. Patient specific (PS-PTV): Union of CTV from PCT and first 5 CBCT formed an “occupancy volume” (OV). PS-PTV Z 0.3 cm + OV 2. Multi-image plan of day (MI-POD): 3 library plans were created; Small (2 smallest of CTV from PCT and first 5 CBCT used to create OV. PTV Z OV + 3 mm), Medium (same as PS-PTV) and Large (1.5 cm + CTV from PCT) 3. Single image plan of day (SI-POD): Plan library created using PCT alone. Small (1.5 cm to CTV in all directions except -1.0 cm superiorly), Medium (1.5 cm in all directions except -0.5 cm superiorly) and Large (1.5 cm in all directions except 0 cm superiorly) Standard PTV (1.5 cm + CTV from PCT) was used for dose accumulation for first 5 fractions in PS-PTV & MI-POD. PTV in each strategy that fully contained the bladder on registered CBCT/fraction was recorded. Daily CBCTs were registered using deformable image registration with PCT; dose was computed on each CBCT and deformably accumulated on PCT. The PTV, CTV D99 and rectum D30 for each strategy were compared using Wilcoxon Signed Rank test or paired Student’s t test (where appropriate) with a 2-tailed p0.05 considered statistically significant. Results: Median PTV for each strategy was: SI-POD 480.9 cc, PS-PTV 391.8 cc and MI-POD 451.8. CTV D99 and median of difference in the PTV are shown below: Abstract 2636
Abstract 2635
Age (v 70) 71-80 >80
2636
Strategy
HR
95%CI
p
1.27 1.69 1.21 1.71 1.08 0.86 0.91 1.02 0.96 1.06 1.30 1.91 0.91 0.99 1.34
1.08-1.50 1.43-1.99 1.06-1.40 1.42-2.06 0.90-1.31 0.71-1.04 0.76-1.10 0.86-1.21 0.79-1.17 0.81-1.39 1.09-1.56 1.59-2.30 0.65-1.28 0.88-1.12 0.93-1.92
<0.01 <0.01 0.01 <0.01 0.41 0.12 0.34 0.84 0.69 0.66 <0.01 <0.01 0.60 0.89 0.12
adjusted for race, gender, and insurance.
Mean CTV D99 in Gy with 95% CI p values compared to SI-POD
Median of difference in the PTVcc compared to SI-POD [IQR]
SI-POD 52.9 [95% CI 52.2 e 53.7] PS-PTV 53.0 [95% CI 52.2 e 53.7, pZ0.88] 113 [82.5 e 145.7, p<0.001] MI-POD 53.0 [95% CI 52.3 e 53.7, pZ0.61] 76.5 [50.3 e 110.2, p<0.001]
Median rectum D30 was: SI-POD 36.7 Gy, PS-PTV 26.2 Gy and MIPOD 26.8 Gy. Rectal sparing was significantly better with PS-PTV and MI-POD compared to SI-POD; median of difference in rectum D30 compared to SI-POD was: PS-PTV 5Gy [pZ0.002] and MI-POD 5.3 Gy [pZ0.001] with no difference in median between PS-PTV and MI-POD, 0Gy [pZ0.509]. Conclusion: Our study demonstrated that a PTV based on multiple images (PS-PTV and MI-POD) provided superior rectal sparing while maintaining adequate target dose compared to single image strategy (SI-POD). However as MI-POD is relatively resource intensive, PS-PTV may be a preferred adaptive strategy for bladder cancer radiotherapy.