High-Intensity Local Radiation Linked to Improved Survival in HNSCC

Zachary S. Zumsteg, MD

High-intensity local radiation combined with systemic therapy improved overall survival (OS) compared with systemic therapy alone in patients with head and neck squamous cell carcinoma, according to findings published in the journal Cancer.

In an analysis of data from the National Cancer Database, investigators found that 2-year OS was 34.2% with high-intensity local therapy compared with 20.6% for systemic therapy (P <.001).

High-intensity local therapy was defined as 1) the receipt of a cumulative radiation dose to the head and neck ≥60 Gy, 2) oncologic surgery to the primary site such as pharyngectomy, subtotal or total laryngectomy, or partial, hemi-, or total glossectomy; 3) or both. Lower intensity local therapy was defined as radiation to the head and neck at doses <60 Gy or more limited surgical procedures, such as local tumor destruction, local tumor excision, biopsy, cryosurgery, electrocautery, photodynamic therapy, or laser ablation, unless head and neck radiotherapy the patient also received was to doses ≥60 Gy.

Only patients assigned to high-intensity radiation enjoyed a survival benefit; survival for patients receiving lower-intensity local treatment was similar to that of patients receiving systemic therapy without local treatment.

“We believe that despite the limitations of this observational data set, our study provides the clearest information to date regarding the benefit of high-intensity local therapy for patients with metastatic HNSCC undergoing systemic therapy,” first author Zachary S. Zumsteg, MD, department of Radiation Oncology, Cedars-Sinai Medical Center, and coinvestigators wrote.

“Although optimal patient selection remains uncertain, we observed a benefit across virtually all subgroups of patients. We believe that the role of combined high-intensity local therapy and systemic therapy in HNSCC patients presenting with [distant metastases] warrants a prospective evaluation, particularly for patients with oligometastatic disease,” added Zumsteg et al.

Investigators reviewed data collected at more than 1500 medical centers from 2004 to 2012. A total of 3269 patients who underwent systemic treatment for invasive squamous cell carcinoma of the nasopharynx, oropharynx, oral cavity, larynx, or hypopharynx and presented with distant metastases were included in this analysis.

Overall, 45.7% of patients received high-intensity local treatment, 19.9% received low-intensity, and 34.4% received no local treatment. All patients received systemic therapy. Of patients who received high-intensity treatment, 1299 received radiation, 121 received surgery, and 75 received both.

The 2-year OS rates were 40.5% for patients receiving high-intensity treatment, 19.8% for low-intensity, and 20.6% for no local treatment (P <.001). Median follow-up for surviving patients was 51.5 months.

Investigators noted that the benefit associated with high-intensity treatment was time-dependent. When investigators studied the treatment effect within 6 months of diagnosis and after 6 months of diagnosis, they found that the survival benefit was stronger in the earlier period (adjusted hazard ratio [AHR] for ≤6 months, 0.255; 95% CI, 0.210-0.309; P <.001 vs AHR for >6 months, 0.622; 95% CI, 0.561-0.689; P <.001).

Zumsteg et al conducted a subgroup analysis of 1059 patients accounting for the number and location of organs with confirmed presence or absence of lung, liver, bone, and brain metastases. As in the overall cohort, patients in this group who received high-intensity treatment had improved survival in comparison with other patients in propensity score—matched cohorts when the number and location of metastatic anatomic sites were included in the propensity score (2-year OS, 39.6% vs 18.4%; P <.001).

Similarly, systemic treatment with high-intensity local therapy was independently associated with improved survival compared with systemic therapy alone (AHR for 6 months, 0.329; 95% CI, 0.236-0.459; P <.001; AHR for >6 months, 0.595; 95% CI, 0.490-0.723; P <.001). There was no difference in survival associated with lower intensity local therapy (HR, 1.10; 95% CI, 0.907-1.334; P = .333) after adjusting for the number and location of metastatic anatomic sites in multivariate models.

The presence of 3 to 4 metastatic sites (HR, 3.429; 95% CI, 2.156-5.454; P <.001) and 2 metastatic sites (HR, 1.801; 95% CI, 1.442-2.249; P <.001) were independently associated with poorer survival compared with a single metastatic site. Investigators observed improved survival with high-intensity local therapy both for the subgroup of patients with a single anatomic site involved with metastasis and for patients with multiple sites of metastases (P = .107).

Female sex, stage N3, treatment at an academic center, multiagent systemic therapy, and higher comorbidity were associated with lower utilization of high-intensity local therapy. In contrast, private insurance and residential education level were associated with significantly more frequent use of high-intensity local therapy.

Zumsteg ZS, Luu M, Yoshida EJ, et al. Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the National Cancer Data Base [published online August 17, 2017]. Cancer. doi: 10.1002/cncr.30933.