title: A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes.
abstract: OBJECTIVE
  To determine the feasibility of induction chemotherapy and chemo-IMRT in head and neck squamous cell cancers at risk of bilateral nodal spread (midline tumours) and to evaluate whether bilateral superficial lobe parotid-sparing IMRT can reduce the incidence of ⩾G2 subjective xerostomia.
  
  
  METHODS
  Patients with midline tumours were enrolled to a phase II trial to receive induction platinum/5-fluorouracil and concomitant platinum with combined superficial lobe parotid-sparing IMRT. The primary site and involved nodal levels received 65 Gy in 30 fractions (f) and at risk nodal levels, 54 Gy/30f. Incidence of ⩾G2 subjective xerostomia was defined as the primary endpoint. Secondary endpoints included incidences of acute and late toxicities and survival outcomes dependent on human papilloma virus (HPV) status.
  
  
  RESULTS
  One hundred and twenty patients with midline cancers completed treatment between December 2005 and May 2010 with median follow-up of 50 months. Incidences of ⩾G2 acute toxicities were: dysphagia 75%; xerostomia 65%; mucositis 86%; pain 83%; and fatigue 64%. At 12 months, ⩾G2 subjective xerostomia was observed in 21% (17% in HPV +ve). Two-year loco-regional progression-free survival (PFS) was 90.7% (95% CI: 85.2-96.2). According to HPV status, there was a significant difference for 2-year loco-regional PFS, 76.8% (HPV-negative) vs 98.6% (HPV-positive), P=0.001. 2-year overall survival was 93% for HPV-positive compared with 52% for HPV-negative cases, P<0.001.
  
  
  CONCLUSIONS
  Sequential chemotherapy/chemo-IMRT for midline tumours is feasible, with excellent survival outcomes. At 1 year, 21% experience ⩾G2 subjective xerostomia. Two-year survival outcomes differ significantly between HPV-positive and HPV-negative disease, suggesting development of different treatment schedules for the different disease entities.
authors.affiliation: Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (and Surrey), UK.
authors.forename: A B
authors.initials: AB
authors.lastname: Miah
authors.affiliation: Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (and Surrey), UK.
authors.forename: U
authors.initials: U
authors.lastname: Schick
authors.affiliation: 1] Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (and Surrey), UK [2] The Institute of Cancer Research, London, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Bhide
authors.affiliation: 1] Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (and Surrey), UK [2] The Institute of Cancer Research, London, UK.
authors.forename: M-T
authors.initials: MT
authors.lastname: Guerrero-Urbano
authors.affiliation: 1] The Institute of Cancer Research, London, UK [2] Department of Physics, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: C H
authors.initials: CH
authors.lastname: Clark
authors.affiliation: 1] The Institute of Cancer Research, London, UK [2] Department of Physics, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Bidmead
authors.affiliation: Department of Statistics, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bodla
authors.affiliation: Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (and Surrey), UK.
authors.forename: L
authors.initials: L
authors.lastname: Del Rosario
authors.affiliation: Department of Histopathology, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Thway
authors.affiliation: Department of Histopathology, St George's Healthcare, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Wilson
authors.affiliation: Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (and Surrey), UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Newbold
authors.affiliation: 1] Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (and Surrey), UK [2] The Institute of Cancer Research, London, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Harrington
authors.affiliation: 1] Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (and Surrey), UK [2] The Institute of Cancer Research, London, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Nutting
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D010306:Parotid Gland / Q000000981:diagnostic imaging / Q000528:radiation effects*; D011446:Prospective Studies; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D014463:Ultrasonography; D014987:Xerostomia / Q000209:etiology; D055815:Young Adult