title: Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study.
abstract: OBJECTIVE
  The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied.
  
  
  METHODS
  Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]10 = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach).
  
  
  RESULTS
  Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity.
  
  
  CONCLUSIONS
  Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.
authors.affiliation: Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai, India. Electronic address: vmurthy@actrec.gov.in.
authors.forename: Vedang
authors.initials: V
authors.lastname: Murthy
authors.affiliation: Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Masodkar
authors.affiliation: Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Kalyani
authors.affiliation: Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Mahantshetty
authors.affiliation: Department of Surgical Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Bakshi
authors.affiliation: Department of Surgical Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Gagan
authors.initials: G
authors.lastname: Prakash
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Kumar
authors.initials: K
authors.lastname: Prabhash
authors.affiliation: Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Sujata
authors.initials: S
authors.lastname: Ghonge
authors.affiliation: Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Shyamkishore
authors.initials: S
authors.lastname: Shrivastava
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy / Q000706:statistics & numerical data; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000706:statistics & numerical data; D059351:Organ Sparing Treatments / Q000379:methods*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents