Salivary gland tumors are a diverse group of neoplasms, encompassing both benign and malignant types. Although typically slow growing, these salivary tumors are generally located at challenging-to-treat locations including the skull base, oral cavity and oropharynx. Without effective treatment, these tumors are likely to recur and/or invade along critical local structures including cranial nerves, swallowing structures, brainstem and the optic pathways. Patients typically present with a painless lump or swelling in the jaw, cheek, mouth, neck or nose. In some cases, patients also present with facial pain or numbness, facial weakness, difficulty opening the mouth, or trouble swallowing.

Patient Presentation

A 30-year-old female initially presented with a painless lump at the jaw location. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 1-cm mass at the left submandibular gland. The patient underwent a surgical resection, and pathology confirmed T1N0 adenoid cystic carcinoma of the left submandibular gland with close margins and positive perineural invasion.

Treatment

Post-operative adjuvant radiation therapy significantly improves outcomes in many salivary gland tumors. For adenoid cystic carcinomas, postoperative radiotherapy significantly lowers the risk of long term local failures (13-fold decrease in risk after adjusting for tumor stage) (Ali, Safina, et al. "Long‐term local control rates of patients with adenoid cystic carcinoma of the head and neck managed by surgery and postoperative radiation." The Laryngoscope 127.10 (2017): 2265-2269).

Particle therapy is the preferred form of adjuvant radiation for many salivary gland tumors including adenoid cystic carcinomas. Traditionally, neutron radiotherapy has been shown to provide superior local control when compared with conventional photon techniques. However, neutron radiotherapy also comes with the costs of increased severe late toxicity.  In contrast, there is emerging data showing the advantages of proton therapy in achieving excellent local control while maintaining lower long-term toxicity. Improved treatment planning and delivery with the proton beam allows the clinical team to provide carefully controlled depth of the radiation beam and sharp dose fall-off near critical organs at risks. Optimized proton dose distribution can also achieve increased conformality with the use of multi-field optimization (MFO) pencil beam scanning techniques. These techniques allow us to adequately treat the location of the tumor and any locations for likely microscopic or perineural spread, while allowing us to increase sparing of normal tissues*.

*Side effect profile for protons vs photons are highly dependent upon individual anatomy and scenario. While proton can be beneficial in some scenarios, your provider may also recommend photons over protons in certain scenarios. Please discuss with your provider for tailored-made recommendations in your specific scenario.

Patient Experience

The patient received a biological equivalent dose of 63 cobalt Gy delivered over 30 treatment fractions of proton radiation over 6 weeks. The treatment encompassed the left submandibular gland, ipsilateral upper neck, and coverage of the trigeminal V3 branch to foramen ovale to the skull base. No additional systemic therapy was given. The patient tolerated the treatment well with limited toxicities and is now being seen for routine follow up visits.

A recent study showed that postoperative proton radiotherapy achieved high 3-year loco-regional control rates (95%), progression-free survival (81%) and overall survival (96%) in patients with major salivary gland tumors. This is in comparison of historical studies with photons with 3-year loco-regional control rates at 80-90% and overall survival at 75-80%. Importantly, this study showed favorable toxicity profile  for salivary gland patients undergoing proton treatments. (Zakeri, Kaveh, et al. "Outcomes and prognostic factors of major salivary gland tumors treated with proton beam radiation therapy." Head & neck 43.4 (2021): 1056-1062). Future studies would be needed to directly compare patient outcomes

Finally, studies have shown that proton radiotherapy is associated with a decreased risk of secondary malignancies caused by radiation treatments especially in the head and neck location and especially relevant in this scenario considering the patient’s young age and excellent prognosis (Xiang, Michael, Daniel T. Chang, and Erqi L. Pollom. "Second cancer risk after primary cancer treatment with three‐dimensional conformal, intensity‐modulated, or proton beam radiation therapy." Cancer 126.15 (2020): 3560-3568.)

To refer a patient or find out more about the Johns Hopkins Proton Therapy Center, visit hopkinsproton.org.