Treatment Decision-Making in Head and Neck Cancer

Kristin Daly, MSN, ANP-BC, AOCNP

Suppose you have a patient who is a 57-year-old Caucasian male, with a squamous cell carcinoma of the left tonsil. This patient has a history of 10 pack-years, although he quit 15 years ago. He currently drinks 3 or 4 beers a day and works as a carpenter. This individual has a history of hypertension and hypercholesterolemia.¹

Your patient had received 3 courses of antibiotics at his urgent care and through his primary care provider. Yet, that did not alleviate his pain. He had been dealing with throat soreness, along with a painless, firm, enlarged left neck lymph node, which he thinks has been present for at least 4 months. Of note, he has a full beard, so he did not notice this bump until he began having some difficulty swallowing. He is not sure how long his lymph node has been enlarged.

You conduct an exam. His 2.5-3 cm left level III lymph node is palpated, but a 1.5 cm enlarged painless, firm, fixed lymph to right level IV is also identified—which the patient had not previously noticed.

A pretreatment computed tomography and position emission tomography (PET) scan show that this individual has a hypermetabolic lesion to the left palatine tonsil and that he has bilateral hypermetabolic enlarged lymph nodes, but there is no evidence of distant disease. However, within 4 months of completing his postoperative adjuvant chemotherapy and radiation therapy (POACRT)—which he tolerated well—his PET scan shows a 1.5 cm FDG-avid lesion to his right ilium. This is biopsied, and he is determined to have metastatic p16+ oropharyngeal squamous cell carcinoma (OPSCC).

You order next-generation sequencing testing and PD-L1 testing. You discover that your patient’s disease has a PD-L1 combined positive score (CPS) score of 35% but no other currently actionable variants.

What treatment would you give this patient?

During a presentation at the 2023 JADPRO Live annual conference, Kristin Daly, MSN, ANP-BC, AOCNP, a nurse practitioner at Siteman Cancer Center at Barnes-Jewish Hospital Washington University School of Medicine, answered this question and discussed how providers approach treatment decisions in this patient population.

P16/HPV OPSSCC

As Daly explained, p16 is the most important biomarker in OPSCC in the curative setting; patients whose disease is p16+ are HPV+. When patients are diagnosed, they should undergo p16 testing via immunohistochemistry (IHC) as this is a cost effective and reliable surrogate test for HPV.

If additional testing is needed to confirm that their disease is HPV-related, HPV DNA in situ hybridization may be performed.

“p16 is a diagnostic and prognostic biomarker in non-nasopharyngeal head and neck cancer,” Daly said, noting that p16+ OPSCC is virally driven and has a better prognosis, whereas p12- disease is carcinogen driven and is associated with a worse diagnosis.

Treatment for OPSCC

The staging systems for p16+ disease and p16- disease are separate, which is unique compared to some other cancers.

For patients with p16+ disease, there are only 4 stages, Daly noted, stage I, stage II, stage III, and stage IV. However, for those with p16- disease, there are substages for stage IV disease. P16- staging includes stage I, stage II, stage III, stage IVA, IVB, and IVC (distant metastases).

“Please remember that if someone has a p16-negative cancer and they are stage IVA or IVB, their disease is still potentially curable,” Daly emphasized to the audience, sharing that she once had a patient with a potentially curable disease who had started selling his belongings because his health care team did not explain that his stage 4 disease was potentially curable.

For patients with stage 1 disease, surgery or radiation are firstline treatments. For those whose disease is p16+, definitive chemotherapy and radiation therapy (DCRT) is possible.²

For patients with stage 2 disease, surgery or radiation are also indicated, and DCRT is an option for those with p16+ disease. Daly noted that, at first glance, it may seem that the treatment approaches are the same for these populations, but that is misleading.

“Stage I and II may look the same, but they are really not,” she said. “In stage I, you are more likely to get surgery that can be curative by itself. Every other stage else is going to have to have multi-modality therapy, or at least radiation.”

For patients with stage III disease, or stage IVA disease (p16- only), surgery plus postoperative adjuvant radiation therapy (POART), surgery plus POACRT, and DCRT are all indicated. For those with stage IVB disease, DCRT is indicated.

If patients have IV or IVC disease, then their care will be palliative. The recommended first line treatments in this setting is PD-1/PD-L1 directed immunotherapy, with or without chemotherapy. Pembrolizumab (Keytruda) alone is preferred, followed by nivolumab (Opdivo).

Secondline therapy may include platinum-based chemotherapy, taxane-based treatment, 5-Fu, or cetuximab.

Definitive Chemoradiation

As Daly explained, radiation is a key portion of head and neck cancer treatment. With definitive chemoradiation, the chemotherapy radiosensitizes the tumor cells so that the radiation is more effective.

“High-dose cisplatin with radiation, either after surgery or definitive, is the gold standard category 1 recommendation,” Daly said. This involves either 100 mg/m² very 3 weeks during 6 to 7 weeks of radiation Monday through Friday, or 40 mg/m² of weekly chemotherapy every week during concurrent radiation.

Specific populations may also receive neoadjuvant and adjuvant treatments.

For nurses supporting patients through chemoradiation, there are several adverse events (AEs) to be aware of. These patients may experience oral stomatitis and pain, fatigue, thick oral mucus that is hard to clear, constipation, tinnitus, and trismus or “first bite syndrome.” These patients are also more likely to experience weight loss, require a percutaneous endoscopic gastrostomy (PEG) tube for nutrition, develop acute kidney injury, and to be at risk for infection.

When supporting patients through this treatment, Daly recommends that patients sleep propped up and that they don’t lie down after meals or tube feeding. She encouraged nurses to ensure their patients are taking their nausea medications as needed, along with their pain medications.

She also recommends that patients do a baking soda and salt rinse before they use mouthwash, and that they start a bowel regimen from day 1 to prevent constipation.

Palliative Therapy

For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), PD-L1 is the most important biomarker, Daly stressed. It can indicate whether patients will have a positive response to checkpoint inhibitors.

Although tumor proportion score was the formerly preferred test, CPS via IHC is now the preferred test for this biomarker. Importantly, PD-1 directed therapies are now the recommended first line of palliative therapy.

Current guidelines recommend that patients with a PD-L1 CPS score equal to or greater than 1 receive first-line pembrolizumab monotherapy, or pembrolizumab, platinum, and 5-FU.

If their PD-L1 CPS score is less than 1, then the recommended approach is pembrolizumab, plus platinum and 5-FU.

For patients with a PD-L1 CPS status who are platinum-refractory, the recommendation is either pembrolizumab or nivolumab.

So, How Would You Treat Your Patient?

“We would just give our patient pembrolizumab,” Daly revealed, because his disease has metastasized within 6 months of completing treatment and his disease is platinum resistant.

References

1. Slane K, Daly K. Integrating immunotherapy and precision medicine into the treatment of head and neck cancer. Presented at: JADPRO Live 2023. November 9-12, 2023; Orlando, FL.
2. National Comprehensive Cancer Network. Head and neck cancers. (Version 1.2024). https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf