Magnitude and Timing of GTV Response to Neoadjuvant Chemotherapy and Concurrent Chemoradiation in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Abstract

Curative radiation therapy for locally advanced nasopharyngeal carcinoma (NPC) is based on the gross tumor volume (GTV), but the magnitude and timing of GTV changes during combined modality therapy remain unclear. This study analyzes GTV changes at phases of induction chemotherapy and sequential concurrent chemoradiation therapy (CRT) in patients with locally advanced NPC. Subjects include 13 patients with newly diagnosed stage III-IV NPC who underwent treatment between 2011 and 2014. Criteria for eligibility included 2 cycles of neoadjuvant chemotherapy, at least 5 cycles of concurrent chemotherapy and 3 magnetic resonance imaging (MRI) scans at specific phases of treatment (T0: before treatment, T1: postinduction and T3: 3 months after CRT). Induction phase consisted of 2 cycles of gemcitabine and cisplatin. CRT phase consisted of weekly cisplatin and radiation therapy delivered using volumetric modulated arc therapy (VMAT). The total dose was 70 Gy over 35 daily fractions administered 5 days/week. A subset of 3 patients received an additional MRI 4 to 5 weeks into CRT (T2). Gross tumor volume primary (GTVp) was defined as GTV at the primary site and adjacent retropharyngeal LN when involved. GTVp delineated on gadolinium-enhanced fat-saturation T1weighted MRIs by 2 observers and included primary tumor volume and adjacent involved lymph nodes. Mean values are reported ± 1 standard deviation. Preliminary analysis includes 6 (out of 13) patients. The mean initial GTVp was 62.7±32.8 cc. The mean GTVp response after induction phase was 21.4±12.3% with a mean rate of volume change 0.31±0.19 cc/day which corresponds to 0.56±0.35% daily reduction in volume. Total mean GTVp response after completion of treatment (T3) was 77.6±21.6%. Subgroup analysis of subjects who underwent an additional MRI showed a mean GTV reduction of 42.5±22.6% and a mean rate of volume change of 0.87±0.08 cc/day corresponding to 1.7±0.93% daily reduction in volume (from T1 to T2). Preliminary results suggest that the GTV progressively diminishes following both induction chemotherapy and CRT. The mean GTVp response at 4 to 5 weeks into CRT was twofold higher than the response observed after induction chemotherapy. The rate of volume change observed 4 to 5 weeks into CRT exceeded the rate of change during induction phase threefold. These observations may help delineate the optimal timing of imaging and replanning in the context of adaptive field radiation therapy. Analysis of the full NPC patient dataset is ongoing and will be reported.