A phase I study of dose-escalated chemoradiation with accelerated intensity modulated radiotherapy in locally advanced head and neck cancer
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文摘
Intensity modulated radiotherapy (IMRT) allows the delivery of higher and more homogeneous radiation dose to head and neck tumours. This study aims to determine the safety of dose-escalated chemo-IMRT for larynx preservation in locally advanced head and neck cancer.

Methods

Patients with T2–4, N1–3, M0 squamous cell carcinoma of the larynx or hypopharynx were treated with a simultaneous-boost IMRT. Two radiation dose levels (DL) were tested: In DL 1, 63 Gy/28F was delivered to primary tumour and involved nodes and 51.8 Gy/28F to elective nodes. In DL 2, the doses were 67.2 Gy/28F and 56 Gy/28F, respectively, representing a 9 % dose escalation for the primary. All patients received 2 cycles of neoadjuvant cisplatin and 5-fluorouracil, and concomitant cisplatin. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) were collected.

Results

Thirty patients were entered, 15 in each dose level. All patients completed the treatment schedule. In DL 1, the incidences of acute G3 toxicities were 27 % (pain), 20 % (radiation dermatitis), 0 % (xerostomia) and 67 % required gastrostomy tubes. For DL 2 the corresponding incidences were 40 % , 20 % , 7 % , and 87 % . G3 dysphagia and pain persisted longer in DL 2. With regard to mucositis, a prolonged healing time for DL 2 was found, with prevalence of G2 of 58 % in week 10. No acute grade 4 toxicity was observed. At 6 months, 1 patient in DL 2 had G3 late toxicity (dysphagia). No dose limiting toxicity was found. Complete response rates were 80 % in DL 1, and 87 % in DL 2.

Conclusion

Moderately accelerated chemo-IMRT is safe and feasible with good compliance and acceptable acute toxicity. Dose escalation was possible without a significant difference in acute toxicity. Longer follow-up is required to determine the incidence of late radiation toxicities, and tumour control rates.

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