Multidisciplinary Management of Radiation-Induced Salivary Gland Carcinomas in the Modern Radiotherapy Era.

Domenico Attilio Romanello,Zulfiyya Imamguliyeva,Cesare Piazza,Ester Orlandi,Davide Lombardi,Nicola Alessandro Iacovelli,Pasquale Quattrone,Stefano Cavalieri,Lorenza Gandola,Giuseppina Calareso,Laura Deborah Locati,Marco Guzzo,Barbara Diletto,Barbara Vischioni,Lisa Licitra,Alberto Iannalfi

doi:10.3390/cancers12123769

Abstract

Simple SummaryEtiopathogenesis of salivary gland cancers [SGCs] is largely unknown, even if exposition to ionizing radiation is a recognized risk factor for SGCs development. To date, exhaustive data to guide clinicians in managing patients with radiation-induced [ri] SGCs are scarce and their treatment remains challenging. The purpose of this work is to describe and to analyze clinical and histopathological features, delivered treatments, and outcome of a series of patients with ri-SGCs treated at two Italian cancer referral sites. Given the rarity of ri-SGCs, this retrospective analysis conducted on a case series of 13 patients adds further knowledge to the paucity of literature. The management of these malignancies is extremely complex requiring a multidisciplinary treatment approach.Clinical data of ri-SGCs patients treated between 2015 and 2019 at a tertiary cancer center and a national hadron therapy facility were reviewed. Latent time (LT) from first RT to ri-SGCs diagnosis, overall (OS), and disease-free survival (DFS) were assessed. Thirteen patients developed 14 ri-SGCs (one patient had 2 synchronous ri-SCGs), after a median LT of 23 years (range 16–34). Parotid was the primary site in 8 cases (57%) and salivary duct carcinoma was the most frequent histotype (29%). Nine patients (69%) underwent surgery (Sx). Among them, 4 patients (31%) underwent Sx alone, 5 received post-operative treatments: 3 (23%) photon-based (X) reRT, one (8%) protons and carbon ions, one (8%) carbon ions only. One patient (8%) received definitive XRT. The remaining 3 patients (23%) received androgen deprivation therapy. With a median follow-up of 48 months (range 24–72), median OS and PFS were 74 and 24 months, respectively. In the subgroup of AR+ ri-SGCs, median PFS and OS were 12 and 74 months, respectively. Given the rarity of ri-SGCs, this work adds further knowledge to the paucity of literature. The management of these malignancies is extremely complex requiring a multidisciplinary treatment approach.

Highlights

Malignant tumors of salivary glands (SGCs) comprise less than 0.5% of all cancers and constitute about2–8.5% of head and neck cancers (HNCs) [1]
Positive nodes (n = 3) have been detected in submandibular (n = 2) or minor salivary glands (n = 1) tumors whereas distant metastases were present in 2 cases
Median Latent time (LT) to ri-SGCs was not significantly different whether primary tumor was diagnosed in pediatric age (31 years, range 5–50) or in adult (33.5 years, range 18–68), even though in the former diagnosis of ri-SGCS appeared earlier after primary treatment compared to the latter

Summary

Introduction

Malignant tumors of salivary glands (SGCs) comprise less than 0.5% of all cancers and constitute about2–8.5% of head and neck cancers (HNCs) [1]. Malignant tumors of salivary glands (SGCs) comprise less than 0.5% of all cancers and constitute about. Etiopathogenesis of SGCs is largely unknown, even if exposition to ionizing radiation is a recognized risk factor for SGCs development. This was reported for the first time in Japanese survivors of the atomic bomb: the frequency of SGCs, mucoepidermoid carinoma (MEC) in particular, was disproportionately high at high radiation doses. In Japanese survivors, out of 145 SGCs registered from 1950 to 1987, 41 were malignant and the proportion of MEC raised with the increasing of radiation dose (p = 0.004 for linear trend) [4]. Even doses of 2 Gy could raise the risk of developing salivary gland tumors [4,5]

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