Head and Neck Cancers
Outcomes of Sinonasal Cancer Treated With Proton Therapy

https://doi.org/10.1016/j.ijrobp.2016.02.019Get rights and content

Purpose

To report disease outcomes after proton therapy (PT) for sinonasal cancer.

Methods and Materials

Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients.

Results

The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with grade 3 or higher unilateral vision loss in 2%).

Conclusions

Dose-intensified, hyperfractionated PT with or without concurrent chemotherapy results in excellent LC after gross total resection, and results in patients with gross disease are encouraging. Patients with high-grade histology are at greater risk of death from distant dissemination. Continuous LC is a major determinant of survival justifying aggressive local therapy in nearly all cases.

Introduction

Carcinomas of the sinonasal region are a rare and diverse group of cancers accounting for fewer than 3% of head and neck tumors and fewer than 0.5% of all cancers 1, 2, 3. No prospective randomized clinical trials are available to guide clinical decisions in this disease category. Most patients present with locally advanced disease and will require aggressive multimodality management with surgery, radiation therapy (RT), and chemotherapy 1, 4, 5. However, delivery of local therapy in this region is notoriously challenged by the anatomic constraints from adjacent structures, such as the central nervous system (CNS) and visual pathways. Historically, local control (LC) rates of 50% to 60% were achieved with surgery and adjuvant RT for T3-T4 tumors 1, 4, 5, 6, 7, and primary RT controls disease in fewer patients (8), with high-grade visual toxicity rates of 17% to 35% 6, 9. With adjuvant intensity modulated radiation therapy (IMRT), LC rates have improved to 58% to 75% and visual pathway toxicity rates have significantly declined 10, 11, 12, 13. Nevertheless, the inability to achieve adequate LC remains a significant challenge and is a major driver of mortality.

The dosimetric benefits of proton therapy (PT) can be used to reduce toxicity through normal-tissue sparing or improve disease control through treatment intensification. Multiple dosimetric analyses have shown the potential benefit of PT for this disease site 14, 15, 16, and a recent meta-analysis and systematic review showed a disease control and survival benefit with PT over IMRT for sinonasal cancers (17).

We undertook this study to assess the outcomes of patients systematically treated with either primary or postoperative PT with or without chemotherapy for sinonasal cancers. We report disease control outcomes, survival rates, and major toxicities. We also performed comprehensive analyses of prognostic factors from which we made observations that will continue to help inform the management of these challenging cancers.

Section snippets

Methods and Materials

In compliance with the Health Insurance Portability and Accountability Act and 2 prospective institutional review board–approved outcomes studies, we reviewed the medical records of 84 patients with sinonasal cancers treated between 2007 and 2013 at our institution. The inclusion and exclusion criteria were as follows:

  • Adults (aged >18 years)

  • Curative treatment including primary or postoperative PT for sinonasal cancers excluding mucosal melanomas, sarcomas, and lymphomas

  • No distant metastases

Results

The major survival and disease control outcomes are detailed in Figure 1. Three-year LC, NC, freedom from DM, DFS, CSS, and OS rates were 83%, 94%, 73.2%, 63%, 70%, and 68%, respectively. All but 1 death was attributed to disease or treatment. The crude LC rate was 86%. LRs occurred in 8 patients as a first event (12 total recurrences) at a median of 10.6 months after PT, and only 1 LR occurred after 2 years. DMs with continuous local-regional control occurred in 17 patients. DMs developed

Discussion

To our knowledge, this is the largest reported series of sinonasal cancers treated with PT. We used a strategy of aggressive local therapy including gross total resection (GTR), when feasible, followed by adjuvant dose-intensified accelerated-hyperfractionated double-scattered PT, elective neck RT, and concurrent low-dose weekly cisplatin for most patients. Alternatively, primary PT and concurrent chemotherapy were used in patients for whom surgery was deemed unsuitable or who had gross

Conclusions

In our study LC was the single most important factor that affected the cure rate in patients with sinonasal cancer. Adjuvant hyperfractionated PT after GTR resulted in a high rate of LC (90%), which far exceeded the previously reported LC rate with conventional RT and IMRT. An encouraging 60% of patients with gross disease obtained LC after PT and chemotherapy. Besides LC, high-grade histology was the only other independent predictor of survival on MVA. Patients with high-grade tumors would

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    Conflict of interest: none.

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