Proton radiotherapy in patients with nasopharyngeal carcinoma increases chances of successful treatment

Reducing the risk of early and late side effects of radiotherapy

Nasopharyngeal tumors develop in its posterior wall, and due to their location, standard photon radiotherapy is unsuitable for treatment. The proton modality differs from the photon one in how it absorbs ionizing radiation in tissues – the proton modality has a more favorable distribution of medium and low doses of radiation and a similar distribution in the high-dose area. Low and medium doses of radiation are sources of late and very late side effects of radiotherapy; therefore, its use should be considered in situations where curing the patient or long-term survival is expected.

The second situation where proton use is suitable is the location of tumors near healthy tissues, as these can be damaged by radiation even in the short term, and photon radiotherapy does not allow for the application of doses sufficient to eradicate the tumor. ”It is generally known that even small doses of radiation to the brain lead to reduced intelligence in patients. This phenomenon is extreme in children, but it also applies to adults. In the case of proton therapy, however, the beam does not reach the brain at all. The tumor is very precisely targeted, which spares the surrounding healthy tissues and, among other things, allows for increased radiation doses,” clarifies the head physician of PTC, Associate Professor MUDr. Jiří Kubeš, Ph.D.

Proton therapy also reduces unwanted irradiation of the spinal cord by up to 80% (thus preventing the development of myelopathy) and significantly spares other areas of the head and neck. This, among other things, reduces the risk of vision and hearing impairment, swallowing difficulties, salivation disorders, and the necessity for percutaneous endoscopic gastrectomy (PEG).

Published results of the Prague team

In 2021, a team of experts from the Proton Therapy Center published results of the efficacy of proton radiotherapy and its toxicity in patients with very advanced nasopharyngeal carcinoma in the European Archives of Oto-Rhino-Laryngology. In more than 60% of this patient population, the tumor had invaded through the base of the skull into the brain, yet 80% of the patients were alive 2 years after treatment.

The study group consisted of 40 patients with nasopharyngeal carcinoma who underwent intensity-modulated proton therapy (IMPT) from January 2013 to June 2018. The median age of patients was 47 years, most having locally advanced tumors (8 patients [20%] had stage 2, 18 [45%] had stage 3, 10 [25%] had stage 4A, and 4 [10%] had stage 4B). The median total dose reached 74 GyE (70–76 GyE) in 37 fractions (35–38). Bilateral neck irradiation occurred in all cases, and concurrent chemotherapy was used in 34 out of the 40 patients (85%). The median follow-up period was 24 (1.5–62) months. The two-year overall survival (OS) was 80%, disease-free survival (DFS) was 75%, and local control was 84%.

Acute toxicity was generally mild, despite the large target volumes and concurrent chemotherapy. The most common acute side effects observed by the authors were skin toxicity and dysphagia. In 4 patients (10%), PEG insertion was required, and in 2 patients (5%), severe late toxicity (grade > 3 according to RTOG) was observed, specifically dysphagia and brain necrosis.

The authors summarized their work by stating that IMPT is feasible for patients with nasopharyngeal carcinoma with mild acute toxicity and has promising results despite the large proportion of advanced diseases in the treated group.

Possible side effects of PT

Proton therapy (PT) also has potential side effects: primarily skin reactions (redness and burns on the neck), occurring in about 50% of patients and healing after 3 weeks. Similar reactions can occur on the mucous membranes, causing many patients to be limited to a liquid diet for 2 weeks. Saliva production in the salivary glands is almost always affected – patients experience dryness, a bad taste, or loss of taste. Saliva returns slowly, sometimes not at all. However, these side effects are also experienced by patients undergoing photon radiotherapy.

During therapy, a special facial mask is used to fix the irradiated area. “In some cases, we can also administer calming medication. So far, however, we have not had any case where a patient had to interrupt treatment or required general anesthesia because of the facial mask. Anesthesia is truly a last resort, and we have never had to use it,” concludes Associate Professor Kubeš.

(esr)

Sources:
1. Kubeš J., Vondráček V., Andrlík M. et al. Proton pencil-beam scanning radiotherapy in the treatment of nasopharyngeal cancer: dosimetric parameters and 2-year results. Eur Arch Otorhinolaryngol 2021; 278: 763–769, doi: 10.1007/s00405-020-06175-5.
2. Nádory ORL. Proton Therapy Center Czech. Available at: www.ptc.clinic/co-lecime/hlava-a-krk