SummaryBackgroundThe incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy.MethodsWe did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3–5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080.FindingsBetween Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3–5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2–5·4] with cisplatin vs 4·8 [4·2–5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3–31·0] with cisplatin vs 30·1 [28·3–31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7–14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6–7·2]; p=0·0007).InterpretationCompared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin.FundingCancer Research UK.
The purpose of the study was to evaluate the time effectiveness and dose distribution details of dynamic jaw delivery compared to the regular helical tomotherapy delivery mode in stereotactic body radiation therapy (SBRT) of liver and lung tumors. Ten patients with liver and ten patients with lung tumors were chosen to analyze the dose profiles and treatment times of regular helical tomotherapy delivery (2.5 cm field width) and new helical tomotherapy mode using dynamic jaw delivery with 5 cm field width. A median dose between 24 and 30 Gy was delivered in a single fraction. Regular helical tomotherapy took an average of 31.9 ± 6.7 min (lung SBRT) and 41.7 ± 15.0 min (liver SBRT). A reduction in delivery duration of 38.8% to 19.5 ± 2.9 min could be accomplished for lung irradiation (p < 0.05) and by 50.8% to 20.5 ± 6.0 min for liver SBRT (p < 0.05). Target coverage, as well as conformity and uniformity indices, showed no significant differences. No significant increase in organs‐at‐risk exposure could be detected either for lung or liver tumors. Therefore, use of new delivery mode with dynamic jaws improves treatment efficiency by reducing beam‐on time, while maintaining excellent plan quality.PACS numbers: 87.55.D‐, 87.53.Ly, 87.55.N‐
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