Safe to Spare: Avoiding the Submandibular and Other Salivary Glands During Head and Neck Radiation Therapy

Two recent studies from Cleveland Clinic’s Department of Radiation Oncology demonstrate the safety of sparing the submandibular and other salivary glands to prevent xerostomia when performing radiation therapy on patients with head and neck cancer.

Xerostomia is a common side effect of radiation to the head and neck. The condition can lead to perpetual dry mouth, difficulty speaking and swallowing, and dental decay. While therapies such as cholinergic agonists, acupuncture and sialogogic agents can help alleviate xerostomia and symptoms, primary prevention remains the focus for improvement of patient outcomes.

With that in mind, Cleveland Clinic’s head and neck radiation oncology team recently conducted two retrospective studies of methods for reducing radiation to the areas that produce saliva: the submandibular glands (SMGs) and the oral cavity.

The first study investigated the safety and efficacy of avoiding level IB lymph nodes while treating patients with human papillomavirus (HPV)-associated oropharyngeal carcinoma. The second looked at selectively sparing the SMG when level IB lymph nodes are included in the radiation target. Both studies were published in Oral Oncology.

“Xerostomia can really impact a patient’s quality of life,” says Nikhil Joshi, MD, a radiation oncologist and senior author on the first study. “And that’s especially important to think about with HPV-associated throat cancer patients who tend to be younger and healthier and who have a cancer that is very curable. Whatever we can do to limit side effects for them goes a long way.”

Avoiding level IB is safe

Dr. Joshi and his colleagues also analyzed the records of 86 patients with nonmetastatic T1-2, node-positive, HPV-associated oropharyngeal carcinoma with 172 level IB stations. The patients were treated with definitive or postoperative Intensity-Modulated Radiation Therapy (IMRT) with or without chemotherapy.

The investigators divided the patients into three groups: bilateral level IB targeted (A, N = 16), a single level IB targeted (B, N = 61) and bilateral IB spared (C, N = 9). The majority of patients had unilateral level IB (Group B) station included in the treatment plan.

Of the 172 level IB stations, 93 (54.1 percent) were targeted and 79 (45.9 percent) were avoided. When IB lymph nodes were targeted, the SMG was included in the treatment plan target for all except for four patients whose SMG was carved out of the treatment target. No local or regional recurrences were found at median follow-up for 59.3 months, regardless of whether level IB lymph nodes were included in the treatment plan (P = 0.053). Five-year overall survival (OS) was excellent with no significant difference found among the groups (A: 85.9 percent, B: 91.5 percent, C: 100 percent; P = 0.528)

“We demonstrated the safety of avoiding level IB lymph nodes in this select group of patients. You don’t get any more recurrence than you would expect otherwise, and at the same time you are reducing the doses to the oral cavity and the submandibular glands,” Dr. Joshi says. “And that could eventually lead to lower rates of xerostomia.”

Sparing the SMG

For the second study, investigators analyzed the records of 174 patients with squamous cell cancer (SCC) of the oral cavity or oropharynx, with T1-2, N0-3, M0 disease with at least a single level IB lymph node region included in the target volume. The patients were treated with IMRT with or without chemotherapy.

All but 33 patients had both SMGs intact at time of radiation, while the others had at least one SMG removed during surgery. Of this group, 19 had SMGs within the targeted IB lymph node level spared, and 125 patients had no sparing of their SMG within the targeted 1B lymph node level.

Of the 19 patients with spared SMGs, 18 had clinically positive ipsilateral necks. Of this group, 13 were positive for multilevel disease, most commonly levels II and III.

Locoregional control (LRC) at five years for patients with both SMGs intact was excellent (91.4%). No significant difference was found in LRC of patients with SMGs spared (five-year LRC = 89%) compared with unspared (five-year LRC = 95%) (P = 0.19). Five-year OS was also impressive (83%) and not significantly different in the spared group (five-year OS = 87%) versus the unspared group (five-year OS = 95%) (P = 0.53).

“Our hypothesis for this study was that the submandibular gland itself is very unlikely to harbor cancer,” says Dr. Joshi. “So we thought we could target the space around the gland where lymph nodes can be present and see if there is any benefit. We showed that it was safe and reduces the amount of radiation to the submandibular gland which could eventually result in lower xerostomia rates in these patients.”

Feature image: HPV.