Expert Discusses Optimizing Adjuvant CRT in Head and Neck Cancer

Samuel Swisher-McClure, MD

A recent retrospective, observational cohort study examined use and survival outcomes with adjuvant chemoradiotherapy (CRT) in patients with resected locally advanced head and neck cancer (LAHNC) with negative surgical margins and no extracapsular extension (ECE).

The purpose of the study, said study author Samuel Swisher-McClure, MD, was not to change the standard of care, but to identify patients who would derive greater benefit from CRT.

“The study findings highlight a need to look closer at these patients and improve our selection of patients that are most likely to benefit from chemotherapy,” said Swisher-McClure, an assistant professor of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania.

The analysis included 10,870 patients from the National Cancer Database with AJCC stage III to IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx treated with definitive surgery and adjuvant radiotherapy (RT) or CRT.

Results showed that the use of adjuvant CRT in patients with resected LAHNC with negative surgical margins and no ECE is common. Overall survival was significantly improved with CRT compare to RT alone (HR, 0.90; 95% CI, 0.86-0.94; P <.001). In patients with multiple positive lymph nodes, survival benefits increased with CRT.

OncLive: Could you provide an overview of the study?

In an interview with OncLive, Swisher-McClure discussed the results of the study and steps moving forward in the treatment of patients with head and neck cancer.Swisher-McClure: For patients with locally advanced head and neck cancer who receive surgery as primary therapy, the role of chemotherapy combined with radiation therapy has been previously studied by two randomized control trials. The findings of those 2 trials concluded that patients with these 2 pathological findings—ECE and positive margins—were the patients that benefitted the most from chemotherapy. It was unclear whether patients with other pathologic risk factors should receive chemotherapy with radiation or not.

Our study looked at how patients were treated in real-world practice in this clinical situation over approximately the past decade. We specifically examined patients without traditional indications for chemotherapy to assess how often are they getting chemotherapy and is there any potential benefit seen with the administration of chemotherapy in that setting. We also wanted to try to identify any patients that seem to benefit more from that chemotherapy than others.

The overall findings of this study indicated that large portions of those patients receive chemotherapy, and these are patients for whom there is not level 1 evidence to support its use. We found that about half received more intensive treatment with chemotherapy in addition to radiation therapy. We saw a small benefit associated with the use of chemotherapy in the overall group of patients who received it, in this retrospective study.

When we looked at patients according to number of lymph nodes that were involved by cancer, we found that a higher number of positive lymph nodes was an adverse prognostic factor. However, there was a more substantial benefit associated with chemotherapy in these patients with multiple involved lymph nodes compared to RT alone. On the other hand, we did not observe a benefit with chemotherapy in patients with fewer lymph nodes involved.

This is retrospective research, and it does not define a new standard of care for these patients, but I think that the findings are interesting for several reasons. First a large number of patients in the United States are receiving chemotherapy with RT, which is more intensive and has more side effects, despite uncertainty regarding its benfit. Our study indicates that there are potentially groups of patients who may benefit from chemotherapy, and so I think it underscores the need for additional studies to help better defineuse of adjuvant therapy to improve disease outcomes in these intermediate-risk patients.

What is the next step for patients with head and neck cancer with multiple lymph nodes involved?

What do you think the future holds for adjuvant chemoradiotherapy?

There may be some patients who truthfully will benefit from chemotherapy, but others will just have increased side effects because it’s more toxic treatment, so carefully selecting patients for this more intensive treatment is critical. A key finding is that these patients with multiple lymph nodes involved do worse compared to patients who do not, and so improved adjuvant treatment is needed. I think that this study adds some lower level evidence to help clinicians deciding whether or not to recommend chemotherapy for patients with locally advanced head and neck cancer after surgery. Ultimately prospective studies are needed to better define the benefit of systemic therapy in this settin. One example currently is the RTOG 0920, which randomizes patients without ECE or positive margins, but had multiple lymph nodes or adverse pathologic risk featuresto either radiation alone or radiation plus cetuximab (Erbitux). Results from that trial will hopefully provide more information to help guide treatment in this setting.I think that we have to date tried, in this study and others, to define optimal treatment approaches for patients based on clinical risk factors or pathologic risk factors. I thinkadvances in molecular analysis and geneticsare helping us to better define personalized treatment approaches for patients with cancer in general, including head and neck cancer.

I am optimistic that research moving forward will help us to apply that information in helping to optimize adjuvant therapy approaches for patients with head and neck cancer as well. So, rather than simply going based on the number of lymph nodes, I'm hopeful that in the future we can include genetic analysis of patients’ cancers to help us define how intensive the adjuvant therapy should be and what the risk of recurrence is so that we can more accurately assess the pros and cons of intensive adjuvant therapy, which has toxicities and negative health consequences.

What is the biggest challenge in the treatment of head and neck cancer, currently?

I also think that radiation therapy has been improved through the advanced treatment technologies or proton therapy here at Penn for patients with head and neck cancer after surgery, which helps us reduce radiation dose tonormal tissue, compared to conventional radiation techniques and that can help us improve, or reduce, treatment-related side effects particularly when combined with chemotherapy.A major challenge in head and neck cancer right now is the emergence and rising incidence of HPV-associated oropharynx cancer, which has a distinct natural history and clinical behavior compared to other cancers of the head and neck. The treatment outcomes are substantially better than non-HPV head and neck cancers. There are many ongoing clinical trials which aim to help us define optimal treatment for such patients, and those trials are largely focusing on de-intensification of therapy with the goal of reducing treatment-related side effects and improving long-term patient quality of life while maintaining these very good, cancer-related survival outcomes.

Trifiletti DM, Smith A, Mitra N, et al. Beyond positive margins and extracapsular extension: evaluating the utilization and clinical impact of postoperative chemoradiotherapy in resected locally advanced head and neck cancer [published online February 13, 2017]. J Clin Oncol. doi: 10.1200/JCO.2016.68.2336.