Induction Chemotherapy Response as a Guide for Treatment Optimization in Sinonasal Undifferentiated Carcinoma

Abstract

Purpose: Multimodal therapy is a well-established approach for the treatment of sinonasal undifferentiated carcinoma (SNUC); however, the optimal sequence of the various treatments modalities is yet to be determined. This study aimed to assess the role of induction chemotherapy (IC) in guiding definitive therapy in patients with SNUC.

Methods: Ninety-five previously untreated patients diagnosed with SNUC and treated between 2001 and 2018 at The University of Texas MD Anderson Cancer Center were included in the analysis. Patients were treated with curative intent and received IC before definitive locoregional therapy. The primary end point was disease-specific survival (DSS). Secondary end points included overall and disease-free survival, disease recurrence, and organ preservation.

Results: A total of 95 treatment-naïve patients were included in the analysis. For the entire cohort, the 5-years DSS probability was 59% (95% CI, 53% to 66%). In patients who had partial or complete response to IC, the 5-year DSS probabilities were 81% (95% CI, 69% to 88%) after treatment with definitive concurrent chemoradiotherapy (CRT) after IC and 54% (95% CI, 44% to 61%) after definitive surgery and postoperative radiotherapy or CRT after IC (log-rank P = .001). In patients who did not experience at least a partial response to IC, the 5-year DSS probabilities were 0% (95% CI, 0% to 4%) in patients who were treated with concurrent CRT after IC and 39% (95% CI, 30% to 46%) in patients who were treated with surgery plus radiotherapy or CRT (adjusted hazard ratio of 5.68 [95% CI, 2.89 to 9.36]).

Conclusion: In patients who achieve a favorable response to IC, definitive CRT results in improved survival compared with those who undergo definitive surgery. In patients who do not achieve a favorable response to IC, surgery when feasible seems to provide a better chance of disease control and improved survival.

FIG 1.

Treatment group schemes and responses to treatment. Flowchart describing patient response to therapy and definitive treatment disposition. CR, complete response; CRT, chemoradiotherapy; PR, partial response; RT, radiotherapy.

FIG 2.

Response to therapy and survival outcomes. T1 gadolinium–enhanced magnetic resonance images demonstrating complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).

FIG 3.

Survival outcomes according to definitive locoregional treatment after induction chemotherapy. Disease-specific and overall survival in patients treated with concurrent chemoradiotherapy (CRT; blue) and surgery followed by radiotherapy (RT) or concurrent CRT (red).

FIG 4.

Survival outcomes according to definitive locoregional treatment by response to induction chemotherapy (IC). (A) Disease-specific and (B) overall survival in patients who responded to IC and were treated subsequently with concurrent chemoradiation (CRT; blue) or surgery followed by radiotherapy (RT) or concurrent CRT (red), and in patients who did not respond to IC and were treated subsequently with concurrent CRT (green) and surgery followed by RT or concurrent CRT (orange).

FIG A1.

(A) Disease-free survival of patients who responded to induction chemotherapy (IC), and (B) disease-free survival, (C) locoregional-free survival, and (D) distant metastasis–free survival according to the definitive locoregional treatment in patients who responded to IC. CRT, chemoradiotherapy; RT, radiotherapy.