HNSCC Treatment Failure Patterns, Post-Recurrence Outcomes Described

Researchers identify factors affecting treatment failure patterns and post-recurrence survival in patients with head and neck squamous cell carcinoma treated with modern definitive therapy

medwireNews: A single-centre study of patients with head and neck squamous cell carcinoma (HNSCC) treated with contemporary chemoradiotherapeutic regimens suggests that several factors, including disease subsite and extent of metastases, can influence treatment failure and post-recurrence survival.

The researchers explain that the accurate analysis of recurrence patterns and outcomes in HNSCC patients “can be significantly affected by variations or errors in radiation target delineation”, potentially hampering the interpretation of multicentre trials.

“As such, this large, single-institution study in which patients were treated in a relatively uniform manner minimizes the confounder of variation in the quality of locoregional treatment with that of biologically aggressive disease and allows for analysis of the true patterns of recurrence and natural history after adequate treatment”, they write in JAMA Oncology.

Of 1000 patients with stage III–IVB HNSCC treated between 2001 and 2013 at a US centre, the 703 with oropharyngeal carcinoma (OPC), 126 with laryngeal carcinoma, and 46 with hypopharyngeal carcinoma received definitive intensity-modulated radiotherapy (IMRT), while the remaining 125 oral cavity carcinoma (OCC) patients were given postoperative IMRT. All patients could receive concurrent chemotherapy if considered appropriate, and 90.8% did so.

The cumulative incidence of local failure at 5 years was highest among OCC patients, at 21.3%, and lowest among those with OPC, at 4.2%, with intermediate rates observed in the laryngeal carcinoma and hypopharyngeal carcinoma groups, at 11.4% and 11.1%, respectively.

Overall survival (OS) following locoregional failure was comparable between tumour subtypes, with the only difference seen within the OPC group, such that patients positive for human papillomavirus or p16 had significantly longer survival than those negative for either marker, at a median of 36.5 versus 13.6 months.

On the other hand, median OS after developing distant metastases was significantly shorter for patients with OCC than for their counterparts with other tumour subtypes, at 3.9 months compared with 12.9 months for the non-OCC group.

Multivariate analysis showed that receipt of salvage surgery was significantly associated with improved survival after locoregional failure (hazard ratio [HR]=0.51), whereas the presence of a single metastatic tumour was one of the significant predictors of prolonged post-metastasis survival (HR=0.32). Specifically, OS was a median of 25.7 months for individuals with a solitary metastasis, compared with 11.3 and 7.5 months for those with two to four or at least five metastatic lesions, respectively.

Lead researcher Nadeem Riaz, from the Memorial Sloan Kettering Cancer Center in New York, USA, and colleagues conclude that “[t]hese findings have important implications for clinical trials assessing treatment de-escalation and approaches for patients with recurrent or metastatic HNSCC, particularly those with oligometastatic disease.”


Leeman JE, Li J-G, Pei X, et al. Patterns of treatment failure and postrecurrence outcomes among patients with locally advanced head and neck squamous cell carcinoma after chemoradiotherapy using modern radiation techniques. JAMA Oncol; Advance online publication 25 May 2017. doi: 10.1001/jamaoncol.2017.0973

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