Prospective phase 1 study assessing feasibility of IMRT and IGART to deliver simultaneous integrated high-dose tumor boost (up to 70 Gy) for the radical treatment of localized muscle-invasive bladder cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 307-307
Author(s):  
Shaista Hafeez ◽  
Karole Warren-Oseni ◽  
Helen McNair ◽  
Vibeke Hansen ◽  
Fiona McDonald ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Dose Escalation ◽  
Normal Tissue ◽  
Cone Beam Ct ◽  
Phase 1 ◽  
Randomised Trial ◽  
Late Toxicity ◽  
High Dose ◽  
Normal Bladder ◽  
Muscle Invasive

307 Background: Advances in IGART offer individualized solutions to improve target coverage and reduce normal tissue irradiation allowing opportunity to increase radiation tumour dose and spare normal bladder. Methods: A library of 3 IMRT plans were created (small, medium and large) from planning CT scans performed at 30 and 60 minutes; treating whole bladder to 52 Gy and tumour to 70 Gy in 32 fractions. Where normal tissue dose constraints were not met consideration was made to boosting tumour to lower dose (68 Gy-64 Gy). Cone beam CT (CBCT) imaging was performed prior to each fraction. Appropriate PTV was selected from the library for treatment delivery. Post treatment CBCT was acquired weekly in order to assess intra-fraction filling and coverage. Results: 22 patients have been planned using this technique. All have met tissue constraints for treatment to 70 Gy. 21 patients have completed radiotherapy, 18 completed treatment to 70 Gy; 1 patient was planned and treated to 68 Gy prior to dose escalation using this technique; 1 patient was treated to a total dose of 65.6 Gy because dose limiting toxicity occurred before dose escalation. 572 CBCTs have been evaluated. Treatment was delivered using small, medium, and large plans in 35%, 52%, and 13% cases respectively. Mean intra-fraction filling was 14 cm3 (SD 16.3, range 0.23-107.9). Mean time between pre- and post-CBCTs was 13 min (SD 2.1, range 9-18). Mean D 98% as assessed on post-radiotherapy CBCT was 98.7% (SD 1.78, range 89.9-100%). At median follow-up of 8 months (range 1-24 months), 18 patients remain alive and disease free. 2 superficial recurrences and 3 deaths from metastatic bladder cancer have occurred. No muscle invasive recurrences have occurred within this cohort. Using this technique one patient has experienced late toxicity (grade 3 cystitis) 5.3 months after radiotherapy (now resolved). Conclusions: IGART using IMRT to delivery a simultaneous integrated tumour boost is feasible with acceptable toxicity. Trial recruitment continues at 70 Gy and will be evaluated in a randomised trial (RAIDER). Clinical trial information: NCT01124682.

Phase I dose-escalated image-guided adaptive bladder radiotherapy study: Results of first dose cohort (68Gy).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 291-291 ◽  
Author(s):  
Robert Huddart ◽  
Fiona McDonald ◽  
Shaista Hafeez ◽  
Karole Warren-Oseni ◽  
Helen Taylor ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Phase I ◽  
Dose Escalation ◽  
Normal Tissue ◽  
Phase Iii ◽  
High Dose ◽  
Dose Cohort ◽  
Image Guided ◽  
Study Results ◽  
Muscle Invasive

291 Background: Prospective study assessing the safety of dose escalation in the treatment of localised muscle-invasive bladder cancer using image-guided adaptive radiotherapy (RT) with a reduced high-dose tumour volume. Methods: Radical RT was planned and delivered in 3 phases. Phase I was delivered to the empty whole bladder (10Gy 5#). Bladder variation assessed on phase I daily imaging was used to determine the adaptive approach for phase III (composite volume or plan of the day). Phase II was delivered to a tumour boost volume on a partially filled bladder (18Gy 9# if normal tissue dose-constraints were met, or to 14Gy 7# if they were not). The adaptive phase III (40Gy 20#) was delivered to the empty whole bladder. The primary endpoint was late RTOG toxicity. Results: Of the twenty-six patients recruited to 68Gy, 20 patients met the normal tissue constraints for dose escalation. For the phase III adaptive technique, 14 patients were treated with a composite volume approach and 12 with a plan of the day. At median follow-up of 24 months, 13 (65%) dose escalated patients remain alive and disease free. Within this dose cohort there has been 1 muscle invasive local recurrence, 1 superficial recurrence and 1 patient has developed metastases. 5 patients in the dose-escalated group have died; 3 from cardiac events, 1 from hospital acquired pneumonia and 1 from metastatic bladder cancer. 1 patient in the dose-escalated group has experienced grade 3 late toxicity (cystitis) occurring 24.6 months after the end of radiotherapy. Conclusions: Image-guided adaptive RT techniques with reduced high-dose volume allow tumour dose-escalation. Toxicity data to date suggest tolerability of 68Gy. Local disease control rates are promising. Trial recruitment continues at 70Gy using intensity modulated radiotherapy technique to deliver a simultaneous integrated boost. Clinical trial information: 7653.

Outcome of BC2001 patients (CRUK/01/004) who received neoadjuvant chemotherapy prior to randomization to chemo-radiotherapy (cRT) versus radiotherapy (RT).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 298-298 ◽  
Author(s):  
Syed A. Hussain ◽  
Emma Hall ◽  
Nuria Porta ◽  
Malcolm Crundwell ◽  
Peter Jenkins ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Performance Status ◽  
Neoadjuvant Treatment ◽  
Late Toxicity ◽  
Invasive Bladder Cancer ◽  
P Value ◽  
Muscle Invasive Bladder Cancer ◽  
Cox Models ◽  
Muscle Invasive

298 Background: Neoadjuvant chemotherapy is considered standard of care for patients with muscle invasive bladder cancer (MIBC). Gemcitabine plus cisplatin or carboplatin (GC) has been adopted as a standard neoadjuvant regimen for MIBC. BC2001 showed that adding chemotherapy (5FU+MMC) to radiotherapy (55Gy/20f or 64Gy/32f) significantly improved rates of muscle invasive bladder cancer (MIBC) locoregional control (LRC) [James 2012]. We report outcome of patients (pts) receiving neoadjuvant chemotherapy prior to starting BC2001 trial treatment (cRT or RT alone). Methods: Between August 2001 and April 2008, 360 pts were randomised to RT (178) or cRT (182); 117 (32.5%) received neoadjuvant chemotherapy (61 RT, 56 cRT). Primary endpoint was LRC, secondary endpoints included toxicity, overall survival (OS) and metastasis free survival (MFS). Cox models adjusted by known prognostic factors were used to estimate randomised treatment effect in this subgroup of pts. Toxicities were compared by Chi squared tests. Results: Median age of the 117 pts was 66 (interquartile range: 60-73) years, 86% were male, 73% had baseline 0 WHO performance status. 81% had T2 and 87% G3 tumours. Neoadjuvant treatment received was GC (73.5%), MVAC (13.6%), CMV (11.1%) or other (<2%). 92.3% cRT and 91.8% RT pts completed radiotherapy as planned. Grade 3 or above adverse events during treatment occurred in 27.4% pts (32.2% cRT vs 22.9 RT, p-value(p)=0.27), and in 9.5% during follow-up (13.4% cRT vs 5.3% RT, p=0.21). There was a trend for improved LRC in the cRT group (hazard ratio HR=0.64, 95CI% 0.33-1.23, p=0.18), while no differences in OS (HR=0.95, 95CI% 0.57-1.57, p=0.83) or MFS (HR=0.93, 95CI% 0.52-1.65, p=0.80) were observed. Median OS was 46.7 months ,cRT: 50.4 months vs RT: 46.7 months. MFS: Median: 68.5 months, cRT: 118.5 months vs RT: 54.2 months. Conclusions: The benefit in improved LRC of synchronous chemotherapy with 5FU/MMC was also found in the subgroup of BC2001 pts receiving neoadjuvant chemotherapy, with no significant increase in late toxicity. Neoadjuvant chemotherapy did not compromise the delivery of radical curative treatment with RT or cRT. Clinical trial information: ISRCTN68324339.

scholarly journals Quantification and correction of distortion in diffusion-weighted MRI at 1.5 and 3 T in a muscle-invasive bladder cancer phantom for radiotherapy planning

2020 ◽  
Vol 93 (1114) ◽  
pp. 20190710
Author(s):  
Jane Rogers ◽  
Victoria Sherwood ◽  
Sarah C. Wayte ◽  
Jonathan A. Duffy ◽  
Spyros Manolopoulos
Keyword(s):  
Bladder Cancer ◽  
Dose Escalation ◽  
Fiducial Marker ◽  
Radiotherapy Planning ◽  
Invasive Bladder Cancer ◽  
Residual Tumour ◽  
Diffusion Weighted Mri ◽  
Muscle Invasive Bladder Cancer ◽  
Diffusion Weighted ◽  
Muscle Invasive

Objective: Limited visibility of post-resection muscle-invasive bladder cancer (MIBC) on CT hinders radiotherapy dose escalation of the residual tumour. Diffusion-weighted MRI (DW-MRI) visualises areas of high tumour burden and is increasingly used within diagnosis and as a biomarker for cancer. DW-MRI could, therefore, facilitate dose escalation, potentially via dose-painting and/or accommodating response. However, the distortion inherent in DW-MRI could limit geometric accuracy. Therefore, this study aims to quantify DW-MRI distortion via imaging of a bladder phantom. Methods: A phantom was designed to mimic MIBC and imaged using CT, DW-MRI and T2W-MRI. Fiducial marker locations were compared across modalities and publicly available software was assessed for correction of magnetic susceptibility-related distortion. Results: Fiducial marker locations on CT and T2W-MRI agreed within 1.2 mm at 3 T and 1.8 mm at 1.5 T. The greatest discrepancy between CT and apparent diffusion coefficient (ADC) maps was 6.3 mm at 3 T, reducing to 1.8 mm when corrected for distortion. At 1.5 T, these values were 3.9 mm and 1.7 mm, respectively. Conclusions: Geometric distortion in DW-MRI of a model bladder was initially >6 mm at 3 T and >3 mm at 1.5 T; however, established correction methods reduced this to <2 mm in both cases. Advances in knowledge: A phantom designed to mimic MIBC has been produced and used to show distortion in DW-MRI can be sufficiently mitigated for incorporation into the radiotherapy pathway. Further investigation is therefore warranted to enable individually adaptive image-guided radiotherapy of MIBC based upon DW-MRI.

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