Objectives:

This report is an update of a Comparative Effectiveness Review (CER) published in final form in May 2010 on the benefits and harms of radiotherapy (RT) to treat patients with head and neck cancer (CER No. 20). RT modalities included two-dimensional RT (2DRT), three-dimensional conformal RT (3DCRT), intensity-modulated RT (IMRT), and proton-beam RT (PBT).

In this CER update we included 3DCRT, IMRT, PBT, and stereotactic body RT (SBRT). We used the same Key Questions as for CER No. 20, asking whether any of these modalities is more effective than the others (1) in reducing normal tissue toxicity and adverse events, and improving quality of life (QOL); (2) in improving local tumor control, time to disease progression, and survival; or (3) when used in certain anatomic locations or patient subpopulations; and, finally, whether (4) there is more variation in patient outcomes with any modality secondary to user experience, treatment planning, or target volumes.

The main finding of CER No. 20 was that late xerostomia was reduced and QOL domains related to xerostomia were improved in patients treated with IMRT compared with those who received either 3DCRT or 2DRT. Evidence was insufficient to draw conclusions on survival or tumor control, adverse events other than late xerostomia (e.g., mucositis, dysphagia, skin toxicities, or osteoradionecrosis of the jaw), whether patient and tumor characteristics affected relative outcomes, or whether physician experience and treatment characteristics affected relative clinical outcomes such as survival or treatment-associated adverse events.

Data sources:

A medical librarian searched MEDLINE^®, Embase^®, and the Cochrane Controlled Trials Registry for English-language articles. The overall search was performed for a period dating 12 months before the final literature search in CER No. 20 (September 28, 2009) through April 2013. For SBRT, the literature was searched for the period January 1, 1990, through April 2013. The search was updated May 1, 2014. A search of the gray literature included clinical trial registries and information from manufacturers if available.

Review methods:

We sought only comparative studies that reported clinical outcomes and QOL among our populations of interest. In preparing CER No. 20, we found noncomparative studies to be uninformative due to substantial heterogeneity in methods and populations, so we excluded them from the update. Data were abstracted for each Key Question by one reviewer, with independent data verification. The study limitations of randomized controlled trials (RCTs) and other comparative studies were assessed using the U.S. Preventive Services Task Force (USPSTF) criteria. The strength of the body of evidence for specific outcomes was assessed according to the latest guidance in the Agency for Healthcare Research and Quality “Methods Guide for Effectiveness and Comparative Effectiveness Reviews.”

Results:

In two searches, we identified 7,130 unique titles and screened 284 in full text. Of the latter, 14 unique studies (N=1,781) in 15 reports met the inclusion criteria, including one RCT (N=60). In the updated search, we identified a second citation to an RCT. However, the latter included the same patients as the previously identified RCT. Therefore, it was not double-counted in the total number of patients; however, because it reported additional, different outcomes, it was reviewed. In 13 unique studies (14 reports, including the RCT), 3DCRT and IMRT were compared. One study compared 3DCRT and SBRT; none compared IMRT and SBRT. As in CER No. 20, no evidence was identified on PBT. Key outcomes of therapy included overall survival, local control, adverse effects, and QOL. According to USPSTF criteria, the RCT was deemed fair quality, whereas the other 13 studies were graded as poor quality.

Conclusions:

New evidence on the comparative effectiveness of RT modalities for head and neck cancer is limited and heterogeneous for each comparison of 3DCRT versus IMRT or SBRT. We did not identify any evidence for PBT. New moderate-strength evidence enhances the CER No. 20 finding of reduced late xerostomia with IMRT compared with 3DCRT, with no relative change in other conclusions on adverse events or QOL. New evidence was insufficient to draw conclusions about the relative effects of IMRT and 3DCRT on overall survival or locoregional tumor control. New evidence is insufficient to draw conclusions on the comparative effectiveness of 3DCRT or IMRT versus SBRT or PBT.