Patterns of Failure After IMRT and Proton Re-Irradiation for Patients With Recurrent Head and Neck Cancer.

Abstract

In the setting of head and neck (HN) re-irradiation (reRT), the goal is to adequately cover disease with as small a volume as appropriate to minimize normal tissue toxicity without compromising local control. However, it can be a challenge to gauge the extent microscopic disease beyond the gross tumor to be included in the reRT volume. Here, we aim to determine the patterns of failure after HN reRT. Patients treated with curative intent intensity modulated radiation therapy (IMRT) or proton reRT from September 1999 - June 2015 were evaluated. A total of 148 patients with inoperable tumors received definitive reRT (intact) and 61 who underwent salvage surgery received post-operative reRT (postop). Those who had locoregional recurrence (LRR) and intact imaging data were analyzed. Using deformable imaging registration, diagnostic images at time of recurrence were overlaid on reRT treatment plans. The site of recurrence was delineated and evaluated by at least 2 radiation oncologists/radiologist with HN expertise. The patterns of failure were classified into five types based on spatial and dosimetric criteria: A (central high dose, or "in-field"), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose, or "out-of-field"). For patients who had multiple sites of recurrences, each site was classified independently. The kappa statistic was used to assess the inter-observer agreement on failure classification. Of the 209 patients treated, 67 developed LRR. This represented 44 of 148 (30%) intact patients (median dose 66 Gy) and 23 of 61 (38%) postop patients (median dose 60 Gy). Of these, 41 (61%) had imaging data for analysis, representing 47 sites of failures. Median time to failure was 21 weeks (range: 4 - 220 weeks). Patterns of failure among intact reRT were as follows: 13 Type A (39%), 6 Type B (18%), 1 Type C (3%), and 13 Type E (39%). The majority (79%) of failures were either in the high dose field or completely out of field. Interobserver agreement was 0.92. Patterns of failure among postop reRT were as follows: 4 type A (17%), 5 type B (22%), 5 type C (22%) and 5 type D (22%). The majority (56%) of recurrences were within 1 cm of the reconstructive flap bed, 40% recurred in the same primary subsite, and 17% recurred in the 1st echelon nodal level. Interobserver agreement was 0.68. In patients who recurred after reRT, the majority was either within the central high-dose region, or completely outside the high-dose region suggesting poor disease biology. Biologic dose-escalation and or the addition of systemic therapies may offer improved disease control.