title: Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer.
abstract: OBJECTIVE
  Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue.
  
  
  METHODS
  A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A "plan of the day" approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction filling and coverage.
  
  
  RESULTS
  A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D98 (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy.
  
  
  CONCLUSIONS
  Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be evaluated in a randomized trial.
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom. Electronic address: Shaista.Hafeez@icr.ac.uk.
authors.forename: Shaista
authors.initials: S
authors.lastname: Hafeez
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Karole
authors.initials: K
authors.lastname: Warren-Oseni
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Helen A
authors.initials: HA
authors.lastname: McNair
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Vibeke N
authors.initials: VN
authors.lastname: Hansen
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Kelly
authors.initials: K
authors.lastname: Jones
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Melissa
authors.initials: M
authors.lastname: Tan
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Attia
authors.initials: A
authors.lastname: Khan
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Victoria
authors.initials: V
authors.lastname: Harris
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: McDonald
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Lalondrelle
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Kabir
authors.initials: K
authors.lastname: Mohammed
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Thomas
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Thompson
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Pardeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Dearnaley
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Horwich
authors.affiliation: The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Huddart
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D059351:Organ Sparing Treatments / Q000379:methods*; D058958:Organs at Risk / Q000528:radiation effects; D011446:Prospective Studies; D011832:Radiation Injuries / Q000517:prevention & control; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D011859:Radiography; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D061089:Radiotherapy, Image-Guided / Q000379:methods* / Q000706:statistics & numerical data; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods* / Q000706:statistics & numerical data; D013997:Time Factors; D001743:Urinary Bladder / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine