Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis

doi:10.1016/S1470-2045(14)70268-2

The Lancet Oncology

Volume 15, Issue 9, August 2014, Pages 1027-1038

https://doi.org/10.1016/S1470-2045(14)70268-2 Get rights and content

Summary

Background

Malignant tumours arising within the nasal cavity and paranasal sinuses are rare and composed of several histological types, rendering controlled clinical trials to establish the best treatment impractical. We undertook a systematic review and meta-analysis to compare the clinical outcomes of patients treated with charged particle therapy with those of individuals receiving photon therapy.

Methods

We identified studies of nasal cavity and paranasal sinus tumours through searches of databases including Embase, Medline, Scopus, and the Cochrane Collaboration. We included treatment-naive cohorts (both primary and adjuvant radiation therapy) and those with recurrent disease. Primary outcomes of interest were overall survival, disease-free survival, and locoregional control, at 5 years and at longest follow-up. We used random-effect models to pool outcomes across studies and compared event rates of combined outcomes for charged particle therapy and photon therapy using an interaction test.

Findings

43 cohorts from 41 non-comparative observational studies were included. Median follow-up for the charged particle therapy group was 38 months (range 5–73) and for the photon therapy group was 40 months (14–97). Pooled overall survival was significantly higher at 5 years for charged particle therapy than for photon therapy (relative risk 1·51, 95% CI 1·14–1·99; p=0·0038) and at longest follow-up (1·27, 1·01–1·59; p=0·037). At 5 years, disease-free survival was significantly higher for charged particle therapy than for photon therapy (1·93, 1·36–2·75, p=0·0003) but, at longest follow-up, this event rate did not differ between groups (1·51, 1·00–2·30; p=0·052). Locoregional control did not differ between treatment groups at 5 years (1·06, 0·68–1·67; p=0·79) but it was higher for charged particle therapy than for photon therapy at longest follow-up (1·18, 1·01–1·37; p=0·031). A subgroup analysis comparing proton beam therapy with intensity-modulated radiation therapy showed significantly higher disease-free survival at 5 years (relative risk 1·44, 95% CI 1·01–2·05; p=0·045) and locoregional control at longest follow-up (1·26, 1·05–1·51; p=0·011).

Interpretation

Compared with photon therapy, charged particle therapy could be associated with better outcomes for patients with malignant diseases of the nasal cavity and paranasal sinuses. Prospective studies emphasising collection of patient-reported and functional outcomes are strongly encouraged.

Funding

Mayo Foundation for Medical Education and Research.

Introduction

Primary tumours of the nasal cavity and paranasal sinuses are uncommon; their estimated incidence in the USA is 0·556 cases per 100 000 population per year, with a male:female ratio of 1·8:1.¹ About 3–5% of cancers in the upper respiratory and digestive tract are located in the nasal cavity and paranasal sinuses. The most common histological type is squamous-cell carcinoma (51·6%); other findings include adenocarcinoma (12·6%), olfactory neuroblastoma (6·3%; also known as aesthesioneuroblastoma), adenoid cystic carcinoma (6·2%), melanoma (6·6%), and undifferentiated carcinoma (3·1%). In view of the rarity of cancer at this anatomical site, and because of the multiplicity of histological types, no randomised clinical trials have been completed to generate treatment recommendations.

Management of this heterogeneous group of malignant diseases is challenging. These cancers commonly present as locally advanced disease in close proximity to vital healthy structures of the anterior skull base—eg, the brain, brainstem, eyes, cranial nerves, and optic pathways. Although surgery is the mainstay of treatment for early-stage disease that is resectable, a multimodality approach—with use of postoperative radiation therapy—is needed to augment local control of advanced disease with positive or close surgical margins and perineural spread. Radiation therapy is also used as the primary treatment for patients who are not candidates for definitive surgery and for those with unresectable recurrent disease. The dose of radiation therapy that can be administered safely is, again, limited by the proximity of vital healthy tissue.

Treatment outcomes for patients with tumours of the paranasal sinus and nasal cavity have historically been poor. Technological advances in surgery and conformal targeted radiation therapy—eg, intensity-modulated radiation therapy and charged particle therapy—give us hope that improvements in treatment outcomes could be achieved by escalating the radiation dose to the tumour target volume and lowering the radiation dose to surrounding vital healthy structures.² In a review by Dulguerov and colleagues,³ the proportion of patients with these cancers who survived for 5 years (regardless of type of radiation therapy) increased from 28% in the 1960s to 51% in the 1990s. The unique physical properties of charged particle therapy—with rapid fall-off of dose beyond the Bragg peak (a sharp deposition of dose at a specific depth in tissue)—and its greater relative biological effectiveness compared with photon therapy might further augment treatment outcomes, not only by reducing the incidence and severity of complications but also by allowing an escalation in radiation dose to improve tumour control and survival, which cannot be achieved with photon therapy. In view of the rarity of paranasal sinus and nasal cavity malignant disease, the time and number of institutions needed to complete a clinical trial, and the current cost of charged particle therapy treatment facilities, undertaking a randomised clinical trial to compare outcomes of photon therapy and charged particle therapy is not feasible. Therefore, we did a systematic review and meta-analysis of published work to compare treatment outcomes with charged particle therapy and photon therapy for management of paranasal sinus and nasal cavity malignant diseases.

Section snippets

Study design

We developed a protocol that defined inclusion criteria, search strategy, outcomes of interest, and analysis plan. The reporting of this systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.⁴

Procedures

To identify studies for inclusion in our systematic review and meta-analysis, we did a broad search of six databases, including Embase, Medline, Medline In-Process & Other Non-Indexed Citations, Scopus, the Cochrane Central Register of

Results

539 studies were identified from the database search, of which 205 reports were retrieved for full-text evaluation. 41 non-comparative observational studies met the inclusion criteria and were included in this systematic review (figure 1). We did not find randomised controlled trials or controlled studies that compared charged particle therapy with photon therapy directly. Table 1 shows the characteristics of the included studies.

From the 41 studies, 43 cohorts were identified. 30 cohorts were

Discussion

The findings of our systematic review and meta-analysis suggest that the theoretical advantages of charged particle therapy might in fact be real. We noted better locoregional control, disease-free survival, and overall survival in all patients (treatment-naive and those with recurrent disease) who were treated with charged particle therapy, compared with those receiving photon therapy, at either 5 years or at longest duration of treatment, or both periods. A non-significant improvement in

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ArticlesCharged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design

Procedures

Results

Discussion

Control Clin Trials

Int J Radiat Oncol Biol Phys

Oral Oncol

Int J Radiat Oncol Biol Phys

Am J Otolaryngol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Oral Oncol

Int J Radiat Oncol Biol Phys

J Clin Neurosci

Otolaryngol Head Neck Surg

Int J Radiat Oncol Biol Phys

Clin Oncol (R Coll Radiol)

Radiother Oncol

Int J Radiat Oncol Biol Phys

Am J Otolaryngol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Pract Radiat Oncol

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Incidence and survival in patients with sinonasal cancer: a historical analysis of population-based data

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The potential benefit of radiotherapy with protons in head and neck cancer with respect to normal tissue sparing: a systematic review of literature

Oncologist

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Cancer

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

BMJ

The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses

The use of confidence of fiducial limits illustrated in the case of the binomial

Biometrika

Interaction revisited: the difference between two estimates

BMJ

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Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis