Carbon Ion Beam Boost Irradiation in Malignant Tumors of the Nasal Vestibule and the Anterior Nasal Cavity as an Organ-Preserving Therapy

Abstract

BackgroundSurgery and radiotherapy are current therapeutic options for malignant tumors involving the nasal vestibule. Depending on the location, organ-preserving resection is not always possible, even for small tumors. Definitive radiotherapy is an alternative as an organ-preserving procedure. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of the current study was to analyze toxicity, local control (LC), and organ preserving survival (OPS) after irradiation of carcinoma of the nasal vestibule with raster-scanned carbon ion radiotherapy boost (CIRT-B) combined with volumetric intensity modulated arc therapy (VMAT) with photons.MethodsBetween 12/2015 and 05/2021, 21 patients with malignant tumors involving the nasal vestibule were irradiated with CIRT-B combined with VMAT and retrospectively analyzed. Diagnosis was based on histologic findings. A total of 17 patients had squamous cell carcinoma (SCC) and 4 had other histologies. In this series, 10%, 67%, and 24% of patients had Wang stages 1, 2, and 3 tumors, respectively. Three patients had pathologic cervical nodes on MRI. The median CIRT-B dose was 24 Gy(RBE), while the median VMAT dose was 50 Gy. All patients with pathologic cervical nodes received simultaneously integrated boost with photons (SIB) up to a median dose of 62.5 Gy to the pathological lymph nodes. Eight patients received cisplatin chemotherapy. All patients received regular follow-up imaging after irradiation. Kaplan–Meier estimation was used for statistical assessment.ResultsThe median follow-up after irradiation was 18.9 months. There were no common toxicity criteria grade 5 or 4 adverse events. A total of 20 patients showed grade 3 adverse events mainly on skin and mucosa. All patients were alive at the end of follow-up. The median OPS after treatment was 56.5 months. The 6- and 24-month OPS were 100% and 83.3%, respectively. All local recurrences occurred within 12 months after radiotherapy. The median progression free survival (PFS) after treatment was 52.4 months. The 6-, 12-, and 24-month PFS rates were 95%, 83.6%, and 74.3%, respectively.ConclusionCIRT-B combined with VMAT in malignant tumors of the nasal vestibule is safe and feasible, results in high local control rates, and thus is a good option as organ-preserving therapy. No radiation-associated grade 4 or 5 acute or late AE was documented.

Organization and operation of multi particle therapy facilities: the Marburg Ion-Beam Therapy Center, Germany (MIT)

“…The focus of clinical research at MIT is the treatment of primary and relapsed CNS tumors, especially glioblastomas [10,11], but also on the treatment of head and neck squamous cell carcinoma (HNSCC), especially in critical areas like the nasal areas or ears [12]. MIT is involved in six clinical studies:…”

“…Currently carbon ion irradiation is used for head and neck tumors located in critical areas (f.i. nasal cavity, ear) [12] or in second-line treatment [16][17][18] with good clinical results that argue for a broader clinical practice. Moreover, the multifaceted mechanisms of therapy resistance, exhibited by HNSCC tumors, such as inflammatory and immune-modulating cytokine and chemokine signaling or overstimulation of the PI3K/AKT/TOR signaling pathway are alleviated for carbon ion irradiation [19,20].…”

Squamous cell carcinoma of the nasal vestibule in the Netherlands: A clinical and epidemiological review of 763 cases (2008–2021)

“…For early-stage disease (cT1/2), both primary surgery and radiotherapy yield excellent outcomes. [4][5][6][7][8][9][10][11][12][13][14] Yet, surgery may lead to disfigurement, necessitating additional reconstruction or epithesis. 4,6,15,16 Radiotherapy has the benefit of "organ preservation," but delivery of accurate doses at curvy, thin, superficial targets which are surrounded by air, is not straightforward.…”

“…These tumors are typically easily detectable, allowing for prompt diagnosis at an early stage. For early‐stage disease (cT1/2), both primary surgery and radiotherapy yield excellent outcomes 4–14 . Yet, surgery may lead to disfigurement, necessitating additional reconstruction or epithesis 4,6,15,16 .…”

Validation of the “Rome” Classification for Squamous Cell Carcinoma of the Nasal Vestibule

“…Surgery, with or without adjuvant radiotherapy, is the foundation of treatment for (locally) advanced SCCNV, in particular in the case of bone involvement [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Both surgery and external beam radiotherapy (EBRT) provide great oncological outcomes [ 4 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Brachytherapy (also known as interventional radiotherapy), however, has increasingly become the treatment modality of choice for early-stage SCCNV, as it produces superior survival, aesthetic, and functional outcomes compared to other options [ 6 , 8 , 16 , 19 , 20 , 21 , 22 , 23 , 24 ]; this is mainly because surgery may lead to deformation and require additional reconstruction [ 4 , 10 , 11 , 18 , 23 , 25 ].…”