Combined intensity‐modulated radiotherapy plus raster‐scanned carbon ion boost for advanced adenoid cystic carcinoma of the head and neck results in superior locoregional control and overall survival

Abstract

BACKGROUND:Local control in patients with adenoid cystic carcinoma (ACC) of the head and neck remains a challenge because of the relative radioresistance of these tumors. This prospective carbon ion pilot project was designed to evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost (C12 therapy). The authors present the first analysis of long-term outcomes of raster-scanned C12 therapy compared with modern photon techniques. METHODS: Patients with inoperable or subtotally resected ACC received C12 therapy within the pilot project. Whenever C12 was not available, patients were offered IMRT or fractionated stereotactic radiotherapy (FSRT). Patients received either C12 therapy at a C12 dose of 3 Gray equivalents (GyE) per fraction up to 18 GyE followed by 54 Gray (Gy) of IMRT or IMRT up to a median total dose of 66 Gy. Toxicity was evaluated according to version 3 of the Common Toxicity Terminology for Adverse Events. Locoregional control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed using the Kaplan-Meier method. RESULTS: Fifty-eight patients received C12 therapy, and 37 received photons (IMRT or FSRT). The median follow-up was 74 months in the C12 group and 63 months in the photon group. Overall, 90% of patients in the C12 group and 94% of those in the photon group had T4 tumors; and the most common disease sites were paranasal sinus, parotid with skull base invasion, and nasopharynx. LC, PFS, and OS at 5 years were significantly higher in the C12 group (59.6%, 48.4%, 76.5%, respectively) compared with the photon group (39.9%, 27%, and 58.7%, respectively). There was no significant difference between patients who had subtotally resected and inoperable ACC. CONCLUSIONS: C12 therapy resulted in superior LC, PFS, and OS without a significant difference between patients with inoperable and partially resected ACC. Extensive and morbid resections in patients with advanced ACC may need to be reconsidered. The most common site of locoregional recurrence remains in field, and further C12 dose escalation should be evaluated. Cancer 2015;121:3001-9.

Parotid adenoid cystic carcinoma: Retrospective single institute analysis

“…Its role has been debated, so far [26][27][28]; in our study, patients who received it accordingly to standard treatment concept of radical resection followed by high radiotherapy dose [29], showed a worse prognosis, in contrast with other reports where different radiotherapy protocols showed a significant improvement in local control rate, progression-free disease survival and over-all survival [30]. These controversies might find a reason in the need to find a balance between aggressive surgical procedures to obtain clear margins and the intent to not make post-operative morbidity rate higher than necessary, such as performing facial nerve sacrifice even when there is no macroscopic evidence of disease.…”

Reoperation following the use of non‑standardized procedures for malignant parotid tumors

“…The intact facial nerve preservation rate was 83.3% (25/30); 1 patient with complete facial nerve excision did not undergo a facial nerve graft procedure as complete tumor excision was considered to be the immediate priority, 1 patient with buccal branch excision did not undergo repair surgery for it did not affect important facial function, and the remaining 3 patients with facial nerve branch excision or partial excision underwent facial nerve reconstruction utilizing the great auricular nerve. Facial nerve function was recovered to House-Brackmann (27) grade II in 1 patient and grade III in 2 patients after a 3-month follow-up. A single patient experienced surgical field hemorrhage following surgery and underwent secondary debridement; 1 patient experienced local flap necrosis and an opened incision, and underwent secondary surgery with pectoralis major muscle flap transposition repair; and 2 patients experienced temporary facial paralysis and recovered within 3 months through nutritional support and acupuncture (Table II).…”

“…The dosage of conventional external-beam radiation therapy was 60 Gy in 30 fractions for 6 weeks following reoperation; the maximal local dose was increased to 66-70 Gy in patients with positive surgical margins, and a dose of ≥66 Gy was administered to patients with adenoid cystic carcinoma. Intensity-modulated radiation therapy was administered as follows (27,28): The primary tumor site was defined as the gross tumor volume (GTV) of the tumor bed (GTVtb); the residual tumor was defined as the GTV; the subclinical stage and high-risk lymphatic drainage region was defined as clinical target volume (CTV) 1; and the prophylactic irradiation region of lymphatic drainage was defined as CTV2. The doses of the intensity-modulated radiation therapy following reoperation were as follows: 66-70 GY in 30-33 fractions (6-6.5 weeks) for GTV, 60-66 GY in 30-33 fractions (6-6.5 weeks) for GTVtb, 56-60 GY in 30-33 fractions (6-6.5 weeks) for CTV1, and 54 GY in 30-33 fractions (6-6.5 weeks) for CTV2.…”

Intrafractional dose variation and beam configuration in carbon ion radiotherapy for esophageal cancer

“…Charged particle radiotherapy with carbon ions has been introduced as a new approach to improve radiooncological treatment strategies with a high relative biological effectiveness (RBE) and a high linear energy transfer (LET) compared to conventional photon-based irradiation. Clinical benefit of carbon ion radiotherapy (CIR) has already been demonstrated for other tumor entities [7, 8]. For esophageal cancer, there are some in vitro studies with CIR [9–11] as well as one clinical phase I/II trial from Japan showing first encouraging results [12].…”

“…Our study uses CIR as a boost treatment of the primary tumor on the basis of beneficial bimodal treatment in other entities [8] and preparative to a clinical trial combining a carbon ion boost and elective IMRT of the lymphatic pathways.…”