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

Purpose: 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 locoregional 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.