Phase 1 trial of bevacizumab with concurrent chemoradiation therapy for squamous cell carcinoma of the head and neck with exploratory functional imaging of tumor hypoxia, proliferation, and perfusion.

PURPOSE: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. METHODS AND MATERIALS: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m(2) and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [(18)F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [(61)Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. RESULTS: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. CONCLUSIONS: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates measureable changes in tumor proliferation, hypoxia, and perfusion after bevacizumab monotherapy and during chemoradiation therapy. These findings suggest opportunities to preview the clinical outcomes for individual patients and thereby design personalized therapy approaches in future trials.

Increased local failure risk with prolonged radiation treatment time in head and neck cancer treated with concurrent chemotherapy.

BACKGROUND: Prolonged radiation treatment time (RTT) in head and neck squamous cell carcinoma (HNSCC) is associated with inferior tumor control in patients treated with radiation therapy (RT) alone. However, the significance of prolonged RTT with concurrent chemotherapy is less clear. METHODS: We reviewed outcomes for 171 patients with primary HNSCC treated with curative intent RT and concurrent drug therapy from 2001 to 2009. The effects of RTT and other variables on local control and survival were analyzed. RESULTS: Patients with RTT >7 weeks had a significantly increased risk of local failure (hazard ratio [HR], 2.6; p = .018) and death (HR, 1.9 p = .035). These results retained significance even after adjustment for tumor stage (age was not significant). CONCLUSION: For patients treated with concurrent chemoradiotherapy (chemoRT), prolonged RTT may compromise tumor control as has been established in the setting of RT alone. Symptoms of patients with HNSCC undergoing definitive chemoRT should be managed aggressively to limit treatment interruptions.

Comprehensive IMRT plus weekly cisplatin for advanced head and neck cancer: the University of Wisconsin experience.

BACKGROUND: We retrospectively examined the treatment efficacy and toxicity profile of intensity-modulated radiotherapy (IMRT) plus concurrent weekly cisplatin chemotherapy in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 57 patients with stage III or IV HNSCC were treated with IMRT and concurrent weekly cisplatin (dosed at 30 mg/m(2)) between November 2001 and May 2007. The median prescription dose to the gross tumor volume was 70 Gy (using 2.0-2.2 Gy daily fractions). RESULTS: In-field tumor control at 2 years was 89.1%, locoregional control was 85.5%, and overall survival was 86.9%. The median radiation dose delivered was 70 Gy. The mean dose intensity of cisplatin administered was 25.7 mg/m(2)/week. CONCLUSION: Comprehensive head and neck IMRT to 70 Gy delivered with weekly cisplatin chemotherapy (30 mg/m(2)) is feasible and generally well tolerated.

Bridging gaps in multidisciplinary head and neck cancer care: nursing coordination and case management.

Patients with advanced head and neck cancer face not only a life-threatening malignancy, but also a remarkably complex treatment regimen that can affect their cosmetic appearance and ability to speak, breathe, and swallow. These patients benefit from the coordinated interaction of a multidisciplinary team of specialists and a comprehensive plan of care to address their physical and psychosocial concerns, manage treatment-related toxicities, and prevent or limit long-term morbidities affecting health-related quality of life. Although little has been published on patient-provider communication with a multidisciplinary team, evidence has suggested that gaps often occur in communication between patients and providers, as well as between specialists. These communication gaps can hinder the multidisciplinary group from working toward common patient-centered goals in a coordinated "interdisciplinary" manner. We discuss the role of a head-and-neck oncology nurse coordinator at a single institution in bridging gaps across the continuum of care, promoting an interdisciplinary team approach, and enhancing the overall quality of patient-centered head-and-neck cancer care.