Question 1
For patients with head and neck cancer, how effective is IMRT--compared with 3DCRT and other relevant RT techniques --at reducing normal tissue toxicity and reducing radiation-induced adverse events? Do patients who receive IMRT have better quality of life compared with those who receive 3DCRT or other approaches?

Question 2
For patients with head and neck cancer, what is the effectiveness of IMRT--compared with 3DCRT and other relevant RT techniques--for improving local control, prolonging time to recurrence, or improving survival?

Question 3
Are there specific tumor characteristics or anatomic locations, or specific patient subpopulations (e.g. older vs. younger) for which IMRT would provide greater benefit than does 3DCRT or other RT techniques?

Question 4
Is there evidence of wider variation in outcomes when using IMRT compared with 3DCRT, either because of differences in user experience (years of experience with IMRT, number of patients treated with IMRT, formal training in IMRT), differences in target volume delineation (gross tumor volumes, clinical target volumes, planning target volumes, lymph node regions, organs at risk), or dosimetric parameters (dose to targets, dose constraints for organs at risk)?

Background

Intensity-modulated radiotherapy (IMRT) has been shown to be able to deliver more conformal radiation dose distributions compared with 3-D conformal radiotherapy (3DCRT) or conventional radiotherapy (RT). Because IMRT is relatively new, however, there are still very few prospective studies available directly comparing the clinical effectiveness of IMRT with 3DCRT or conventional RT. It is generally accepted that there are two primary ways in which the more conformal dose distributions from IMRT could potentially result in improved clinical effectiveness: 1) decreasing radiation dose to normal tissues resulting in decreased toxicity, and/or 2) enabling safe dose escalation to the tumor to improve local control (and subsequent survival) without increasing toxicity.

The widespread belief that the improved dose distributions of IMRT will result in improved clinical outcomes is driving the adoption of IMRT as the standard of care in many settings, and in the future it may be difficult to conduct prospective randomized controlled trials to directly compare IMRT with conventional radiation techniques. Therefore, it is critical to understand under what conditions a patient is most likely to receive additional clinical benefit from IMRT compared to other techniques.

Existing research evidence on IMRT effectiveness focuses on head and neck cancer, and prostate cancer. Since IMRT for prostate cancer is already being investigated in a separate comparative effectiveness review, the specific aim of this study is to synthesize the currently available evidence in the literature to determine the clinical effectiveness of IMRT, 3DCRT and other relevant techniques including proton beam therapy for patients with head and neck cancer who are candidates for radiotherapy either as primary or adjuvant treatment.

Outcomes

For the purposes of this study, we define the treatment planning techniques as follows:

• IMRT: Any treatment plan where intensity-modulated radiation beams and computerized inverse treatment planning is used.
• 3DCRT: Any treatment plan where CT-based treatment planning is used to delineate radiation beams and target volumes in three dimensions.
• Conventional RT: Treatment planning where only 2D projection radiographs are used to delineate radiation beams and target volumes.
• The primary outcomes of interest are rates of radiation-induced toxicities and adverse events (both acute and chronic normal tissue toxicity, such as xerostomia, mucositis, taste changes, and dental problems), and their effect on quality of life. The other primary outcomes of interest are clinical effectiveness, including rates of locoregional control, recurrence, and survival.