March 02, 2015
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Recursive partitioning analysis forms new stages for HPV-related oropharyngeal cancer

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Recursive partitioning analysis-based TNM stage groupings were associated with significantly improved survival prediction for patients with HPV-related non-metastatic oropharyngeal carcinomas, according to study results.

Brian O’Sullivan, MD, of Princess Margaret Hospital in Toronto, and colleagues evaluated data from patients with HPV-related (n = 573) and HPV-unrelated (n = 237) non-metastatic oropharyngeal cancer. Patients underwent radiation therapy with or without chemotherapy between 2000 and 2010.

Median follow-up was 5.1 years.

Researchers compared patient survival data with their American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) seventh edition TNM stage.

Survival was significantly associated with TNM stage for patients with HPV-unrelated disease. Five-year OS rates were 70% for patients with stage I disease, 58% for those with stage II disease, 50% for those with stage III disease and 30% for those with stage IV disease (P = .004).

However, 5-year OS did not significantly differ according to TNM stage among patients with HPV-related oropharyngeal cancer (stage I, 88%; stage II, 78%; stage III, 71%; stage IV, 74%).

Using a recursive partitioning analysis, researchers refined AJCC/UICC staging for patients with HPV-related disease into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c) and RPA-III (T4 or N3) stages. RPA-IV would include patients with M1 or metastatic disease.

Patients with RPA-1 disease demonstrated the highest rate of 5-year OS (82%), followed by patients with RPA-II disease (76%) and RPA-III disease (54%; P ˂ .001).

Researchers also developed new staging criteria using adjusted HRs. Although these stages were significantly associated with 5-year OS (P ˂ .01), the survival prediction was greater with the RPA stages.

An RPA that also included RPA stage, patient age and smoking pack-years further improved survival prediction. These stages include group 1 for patients with 20 or fewer pack-years (T1-3N0-N2c), group II for patients with more than 20 pack-years (T1-3N0-N2c), group III for patients aged 70 years or younger (T4 or N3), and group IVA for patients aged older than 70 years (T4 or N3). Five-year OS was significantly associated with these staging groups (group I, 89%; group II, 64%; group III, 57%; group IV, 40%; P ˂ .001).

“This large cohort study suggests that the seventh edition AJCC/UICC TNM staging system is unsuited for HPV-related oropharyngeal cancer but acceptable for HPV-unrelated disease,” O’Sullivan and colleagues concluded. “An RPA-based TNM stage schema is proposed for HPV-related oropharyngeal cancer … Prognostic risk groupings incorporating non-anatomic factors provide additional enhancement.”

These findings may lead to the formal revision of head and neck squamous carcinoma staging criteria, David M. Brizel, MD, of Duke Cancer Institute, wrote in an invited commentary.

“Clearly, the findings of Huang [and colleagues] need to be confirmed and refined both by other institutions and through analysis of larger multicenter and national databases such as SEER,” Brizel wrote. “That said, the AJCC is currently reviewing and revising its head and neck squamous carcinoma staging criteria. The revisions proposed by Huang [and colleagues] offer a first step in the way forward with the potential to identify patients with HPV-positive disease and an unfavorable prognosis via the integration of disease- and patient-specific factors. This process would allow us to more effectively choose treatment for our patients, both in the context of routine care and clinical trials.” – by Alexandra Todak

Disclosure: The researchers report consulting/advisory roles with, research funding from and travel expenses from Elekta. Brizel reports a consulting/advisory role with Pfizer and honoraria from UpToDate Oncology.