Background

Vandetanib, added to cisplatin and radiation therapy (RT) overcomes chemoradiation therapy (CRT) and epidermal growth factor receptor (EGFR) inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models.

Methods

Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) and then vandetanib + RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib + RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2). The primary objective was the maximum tolerated dose (MTD) of vandetanib with RT +/- cisplatin.

Results

Of 33 treated patients, 30 completed therapy (regimen 1, n = 12; regimen 2, n = 18). MTD in regimen 2 was 100 mg (3 dose limiting toxicities [DLTs] at 200 mg), whereas regimen 1 was stopped because of poor recruitment (1 DLT at 200 mg). Most common grade ≥3 adverse events (AEs) were dysphagia (30%), stomatitis (33%), and mucosal inflammation (27%). Five patients discontinued vandetanib because of AEs.

Conclusion

Vandetanib with CRT was feasible.

PURPOSE: This practice parameter for the performance of proton beam radiation therapy was revised collaboratively by the American College of Radiology (ACR) and the American Radium Society (ARS). This practice parameter was developed to serve as a tool in the appropriate application of proton therapy in the care of cancer patients or other patients with conditions in which radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance (QA) standards, indications, and suggested documentation. MATERIALS AND METHODS: This practice parameter for the performance of proton beam radiation therapy was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters - Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. RESULTS: The qualifications and responsibilities of personnel, such as the proton center Chief Medical Officer or Medical Director, Radiation Oncologist, Radiation Physicist, Dosimetrist and Therapist, are outlined, including the necessity for continuing medical education. Proton therapy standard clinical indications and methodologies of treatment management are outlined by disease site and treatment group (e.g. pediatrics) including documentation and the process of proton therapy workflow and equipment specifications. Additionally, this proton therapy practice parameter updates policies and procedures related to a quality assurance and performance improvement program (QAPI), patient education, infection control, and safety. CONCLUSION: As proton therapy becomes more accessible to cancer patients, policies and procedures as outlined in this practice parameter will help ensure quality and safety programs are effectively implemented to optimize clinical care.

Purpose

Previous studies indicate that the benefit of therapy depends on patients' risk for cancer recurrence relative to noncancer mortality (ω ratio). We sought to test the hypothesis that patients with head and neck cancer (HNC) with a higher ω ratio selectively benefit from intensive therapy.

Experimental design

We analyzed 2,688 patients with stage III-IVB HNC undergoing primary radiotherapy (RT) with or without systemic therapy on three phase III trials (RTOG 9003, RTOG 0129, and RTOG 0522). We used generalized competing event regression to stratify patients according to ω ratio and compared the effectiveness of intensive therapy as a function of predicted ω ratio (i.e., ω score). Intensive therapy was defined as treatment on an experimental arm with altered fractionation and/or multiagent concurrent systemic therapy. A nomogram was developed to predict patients' ω score on the basis of tumor, demographic, and health factors. Analysis was by intention to treat.

Results

Decreasing age, improved performance status, higher body mass index, node-positive status, P16-negative status, and oral cavity primary predicted a higher ω ratio. Patients with ω score ≥0.80 were more likely to benefit from intensive treatment [5-year overall survival (OS), 70.0% vs. 56.6%; HR of 0.73, 95% confidence interval (CI): 0.57-0.94; P = 0.016] than those with ω score <0.80 (5-year OS, 46.7% vs. 45.3%; HR of 1.02, 95% CI: 0.92-1.14; P = 0.69; P = 0.019 for interaction). In contrast, the effectiveness of intensive therapy did not depend on risk of progression.

Conclusions

Patients with HNC with a higher ω score selectively benefit from intensive treatment. A nomogram was developed to help select patients for intensive therapy.