According to the results of a Phase III study published early online in Lancet Oncology, the use of accelerated radiotherapy, either alone or in combination with chemotherapy, does not improve outcomes over standard chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). 

The authors note that concomitant chemotherapy and radiotherapy (chemoradiotherapy) is the standard of care in locally advanced HNSCC.  Accelerated radiotherapy has been shown to improve locoregional control in this setting compared to conventional radiotherapy.  The purpose of the current study was to evaluate the safety and efficacy of combining the two.

The study included patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were randomised to receive one of the following treatments:

• conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil; n=279)

• accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil) (n=280), or

• very accelerated radiotherapy alone (64.8 Gy [1.8 Gy twice daily] in 3.5 weeks) (n=281)

The primary endpoint was progression-free survival (PFS).  After a median follow-up of 5.2 years, the main findings were as follows:
 

• Three-year PFS was 37.6% (95% CI 32.1-43.4) after conventional chemoradiotherapy, 34.1% (28.7-39.8) after accelerated radiotherapy-chemotherapy, and 32.2% (27.0-37.9) after very accelerated radiotherapy.

• Accelerated radiotherapy-chemotherapy was not associated with any PFS benefit over conventional chemoradiotherapy (HR 1.02, 95% CI 0.84-1.23; p=0.88)

• Conventional chemoradiotherapy was associated with improved PFS compared with very accelerated radiotherapy (HR 0.82, 0.67-0.99; p=0.041)

• Very accelerated radiotherapy was associated with higher rates of RTOG grade 3-4 acute mucosal toxicity (84% versus 76% in the accelerated radiotherapy-chemotherapy group and 69% in the conventional group).  Accelerated radiotherapy also appeared to be associated with a higher incidence of intubation with feeding tubes during treatment (70%, 64% and 60%, respectively)

The authors note that the most favourable outcomes were seen in the conventional chemoradiotherapy group, and that acceleration of radiotherapy cannot compensate for the absence of chemotherapy.

The authors of a related Comment article say that the overall message from this and other related studies is that treatment intensification does not automatically lead to improved outcomes, and that until proven otherwise, conventionally fractionated radiotherapy combined with three cycles of concomitant platinum-based chemotherapy remains the standard of care in locoregionally advanced head and neck cancer.