A Multi-institutional Comparison of SBRT and IMRT for Definitive Reirradiation of Recurrent or Second Primary Head and Neck Cancer

Abstract

Purpose: Two modern methods of reirradiation, intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT), are established for patients with recurrent or second primary squamous cell carcinoma of the head and neck (rSCCHN). We performed a retrospective multi-institutional analysis to compare methods.

Methods and materials: Data from patients with unresectable rSCCHN previously irradiated to ≥40 Gy who underwent reirradiation with IMRT or SBRT were collected from 8 institutions. First, the prognostic value of our IMRT-based recursive partitioning analysis (RPA) separating those patients with unresectable tumors with an intertreatment interval >2 years or those with ≤2 years and without feeding tube or tracheostomy dependence (class II) from other patients with unresected tumors (class III) was investigated among SBRT patients. Overall survival (OS) and locoregional failure were then compared between IMRT and SBRT by use of 2 methods to control for baseline differences: Cox regression weighted by the inverse probability of treatment and subset analysis by RPA classification.

Results: The study included 414 patients with unresectable rSCCHN: 217 with IMRT and 197 with SBRT. The unadjusted 2-year OS rate was 35.4% for IMRT and 16.3% for SBRT (P<.01). Among SBRT patients, RPA classification retained an independent association with OS. On Cox regression weighted by the inverse probability of treatment, no significant differences in OS or locoregional failure between IMRT and SBRT were demonstrated. Analysis by RPA class showed similar OS between IMRT and SBRT for class III patients. In all class II patients, IMRT was associated with improved OS (P<.001). Further subset analysis demonstrated comparable OS when ≥35 Gy was delivered with SBRT to small tumor volumes. Acute grade ≥4 toxicity was greater in the IMRT group than in the SBRT group (5.1% vs 0.5%, P<.01), with no significant difference in late toxicity.

Conclusions: Reirradiation both with SBRT and with IMRT appear relatively safe with favorable toxicity compared with historical studies. Outcomes vary by RPA class, which informs clinical trial design. Survival is poor in class III patients, and alternative strategies are needed.

Fig. 1.

Comparative overall survival between intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) for recurrent or second primary squamous cell carcinoma of the head and neck across recursive partitioning analysis (RPA) class. (A) Overall survival for all patients. (B) RPA class III—unresectable disease with pre-existing severe airway or swallowing dysfunction. (C) All RPA class II patients. (D) RPA class II with small tumors—unresectable disease with no pre-existing severe airway or swallowing dysfunction and gross tumor volume ≤25 cm³ or rT0 to rT2. (E) RPA class II with large tumors—unresectable disease with no pre-existing severe airway or swallowing dysfunction and gross tumor volume >25 cm³ or rT3 to rT4. Results are stratified by dose.

Fig. 2.

Comparative locoregional control between intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) for recurrent or second primary squamous cell carcinoma of the head and neck across recursive partitioning analysis (RPA) class. (A) Overall locoregional control for all patients. (B) RPA class III—unresectable disease with pre-existing severe airway or swallowing dysfunction. (C) All RPA class II patients. (D) RPA class II with small tumors—unresectable disease with no pre-existing severe airway or swallowing dysfunction and gross tumor volume (GTV) ≤25 cm³ or rT0 to rT2. (E) RPA class II with large tumors—unresectable disease with no pre-existing severe airway or swallowing dysfunction and GTV >25 cm³ or rT3 to rT4. Results are stratified by dose.

Fig. 3.

Comparison between intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) after weighting by inverse probability of treatment (IPTW). (A) Comparison regarding overall survival. (B) Comparison regarding locoregional failure. No significant differences were noted in either comparison after adjustment. Abbreviations: CI = confidence interval; HR = hazard ratio.

Fig. 4.

Cumulative incidence of grade ≥3 late toxicity by treatment technique. Abbreviations: IMRT = intensity modulated radiation therapy; SBRT = stereotactic body radiation therapy.