Acute Toxicity and Efficiency Outcomes in the DARTBOARD Randomized Trial of Daily Adaptive Radiotherapy for Head and Neck Squamous Cell Carcinoma
International Journal of Radiation Oncology*Biology*Physics(2023)
Abstract
Purpose/Objective(s) The clinical utility of adaptive radiotherapy (ART) for head and neck (H&N) squamous cell carcinoma (SqCC) remains poorly defined. Online daily ART (DART) promises both anatomic adaptation and planning target volume (PTV) reduction by developing a unique plan based on the anatomy at each fraction, rendering interfraction setup error negligible. In this prospective trial using CBCT-based ART, patients with H&N SCC undergoing definitive RT (+/- chemotherapy, CRT) were randomized to daily online DART with reduced PTV margins (DART arm) or standard PTV margins without ART (IGRT arm). Materials/Methods Eligibility criteria included a diagnosis of oropharynx, larynx, or hypopharynx SqCC receiving definitive RT or CRT. All individuals received involved nodal radiotherapy (INRT) per a previous institutional study. The gross tumor volume (GTV) received 70 Gy, the primary clinical target volume (CTV) and suspicious nodes received 63 Gy, and nodes on the same level as nodal GTV or identified by an artificial intelligence (AI) algorithm received 56 Gy. The PTV margin in the DART arm was 1mm (2mm S/I), compared to 5mm in the IGRT arm. A H&N radiation oncologist adapted each DART fraction. The primary endpoint was patient-reported xerostomia at one year, requiring enrollment of 50 patients, stratified by oropharynx versus larynx/hypopharynx site. Patients completed the EORTC QLQ30/HN35, MDADI, and the Xerostomia Questionnaire (XQ) patient-reported outcome (PRO) instruments at baseline/1/3/6/12 months after treatment. Results Fifty patients were enrolled (26 IGRT, 24 DART). The cohort consisted of 38 oropharynx and 12 larynx/hypopharynx patients, with AJCC 7th stage I-II (n=4), III (n=10), and IVA/B (n=36). Forty-six patients (92%) were treated with CRT. The mean ipsilateral (16.0 vs. 11.5 Gy, p=0.02) parotid gland and ipsilateral (56.3 vs. 42.2 Gy, p<0.01) and contralateral (36.5 vs. 28.2 Gy, p=0.04) submandibular gland doses were significantly lower with DART. Swallowing OAR doses were not significantly different. The mean total patient in-room, recontouring, and physician at-console times were 33 (SD 5.3), 12.6 (SD 3.4), and 22 (SD 4.4) minutes per adaptive fraction, respectively. There was significantly less G2+ dermatitis in the DART arm (Grade 2+ 31% vs 8%, p=0.05) but not mucositis or dysphagia. No PRO differences were noted at one month, but at three months, trends favored reduced xerostomia with DART (XQ 43.1 vs. 31.2, p=0.2; for oropharynx patients, XQ 45 vs. 28.6, p=0.11). At a median follow-up of 7 months, one in-field, one out-of-field, and two distant recurrences were observed. Conclusion Online DART for H&N SqCC may improve physician- and patient-reported acute toxicity profiles, albeit with increased resource utilization. Additional evidence and follow-up is needed to understand the potential benefits and limitations of this paradigm. The clinical utility of adaptive radiotherapy (ART) for head and neck (H&N) squamous cell carcinoma (SqCC) remains poorly defined. Online daily ART (DART) promises both anatomic adaptation and planning target volume (PTV) reduction by developing a unique plan based on the anatomy at each fraction, rendering interfraction setup error negligible. In this prospective trial using CBCT-based ART, patients with H&N SCC undergoing definitive RT (+/- chemotherapy, CRT) were randomized to daily online DART with reduced PTV margins (DART arm) or standard PTV margins without ART (IGRT arm). Eligibility criteria included a diagnosis of oropharynx, larynx, or hypopharynx SqCC receiving definitive RT or CRT. All individuals received involved nodal radiotherapy (INRT) per a previous institutional study. The gross tumor volume (GTV) received 70 Gy, the primary clinical target volume (CTV) and suspicious nodes received 63 Gy, and nodes on the same level as nodal GTV or identified by an artificial intelligence (AI) algorithm received 56 Gy. The PTV margin in the DART arm was 1mm (2mm S/I), compared to 5mm in the IGRT arm. A H&N radiation oncologist adapted each DART fraction. The primary endpoint was patient-reported xerostomia at one year, requiring enrollment of 50 patients, stratified by oropharynx versus larynx/hypopharynx site. Patients completed the EORTC QLQ30/HN35, MDADI, and the Xerostomia Questionnaire (XQ) patient-reported outcome (PRO) instruments at baseline/1/3/6/12 months after treatment. Fifty patients were enrolled (26 IGRT, 24 DART). The cohort consisted of 38 oropharynx and 12 larynx/hypopharynx patients, with AJCC 7th stage I-II (n=4), III (n=10), and IVA/B (n=36). Forty-six patients (92%) were treated with CRT. The mean ipsilateral (16.0 vs. 11.5 Gy, p=0.02) parotid gland and ipsilateral (56.3 vs. 42.2 Gy, p<0.01) and contralateral (36.5 vs. 28.2 Gy, p=0.04) submandibular gland doses were significantly lower with DART. Swallowing OAR doses were not significantly different. The mean total patient in-room, recontouring, and physician at-console times were 33 (SD 5.3), 12.6 (SD 3.4), and 22 (SD 4.4) minutes per adaptive fraction, respectively. There was significantly less G2+ dermatitis in the DART arm (Grade 2+ 31% vs 8%, p=0.05) but not mucositis or dysphagia. No PRO differences were noted at one month, but at three months, trends favored reduced xerostomia with DART (XQ 43.1 vs. 31.2, p=0.2; for oropharynx patients, XQ 45 vs. 28.6, p=0.11). At a median follow-up of 7 months, one in-field, one out-of-field, and two distant recurrences were observed. Online DART for H&N SqCC may improve physician- and patient-reported acute toxicity profiles, albeit with increased resource utilization. Additional evidence and follow-up is needed to understand the potential benefits and limitations of this paradigm.
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Key words
daily adaptive radiotherapy,neck squamous cell carcinoma,dartboard randomized trial,squamous cell carcinoma
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