Impact of minimum point dose on local control and toxicity in T3-4 nasopharyngeal carcinoma treated with intensity-modulated radiation therapy plus chemotherapy.

Background: We aim to explore the relationship between minimum point dose (Dmin) to the primary gross tumor volume (GTV_P) and local control in treating T3-4 nasopharyngeal carcinoma (NPC).

Methods: Ninety-six non-metastatic T3-4 NPC patients were enrolled between January 2009 and November 2013. Intensity-modulated radiation therapy (IMRT) plus docetaxel, cisplatin and fluorouracil (TPF) chemotherapy was administered. The prescribed dose was 66-70.4 Gy to the GTV_P while maintaining all the critical neurologic organs within dose constraints.

Results: The local response rate was 88.6% after induction chemotherapy. With a median follow-up of 48.5 months, the 3-year local failure-free survival (LFFS) and overall survival (OS) rates were 92.4% and 89.6%, respectively. The average Dmin to the GTV_P was 59.4 Gy (range, 48.3-70.4 Gy). Additionally, 54.0 Gy was identified as the optimal cut-off Dmin to the GTV_P, and the Dmin ≥54.0 Gy group had a better local complete response rate after IMRT (52.4% vs. 81.3%, χ2 = 7.335, P = 0.007), a better 3-year LFFS (95.9% vs. 78.4%, P = 0.005) and a better OS (93.3% vs. 75.9%, P = 0.003). Furthermore, a multivariate analysis found the Dmin to the GTV_P ≥54.0 Gy to be prognostically important for LFFS and OS. One patient (1%) developed asymptomatic temporal lobe necrosis, but no other neurological dysfunctions were observed.

Conclusions: For T3-4-stage NPC treated with IMRT plus TPF chemotherapy, excellent local control with few late toxicities was achieved. A Dmin ≥54.0 Gy to the GTV_P may confer better local control. New ways to increase the Dmin to the GTV_P as far as possible without increasing late toxicities are urgently required.