This prospective, randomized phase II clinical trial evaluated whether daily adaptive radiotherapy (DART), delivered with a 1-mm PTV margin, improves patient-reported xerostomia at one year compared with standard non-adaptive IMRT using a 5-mm margin. Patients with head and neck squamous cell carcinoma were randomized to receive standard IMRT with daily IGRT (Arm 1) or DART (Arm 2). Patient-reported outcomes (PROs) were collected at baseline and during longitudinal follow-up. The Xerostomia Questionnaire (XQ) served as the primary endpoint.

Among the 50 enrolled patients (median age 61.2 years; predominantly male and Caucasian), most had T3–4 disease with nodal involvement and received concurrent chemoradiation. No statistically significant differences in XQ scores were observed between treatment arms when comparing changes from baseline to one year or when evaluating one-year scores directly. Overall one-year PROs were also not significantly different.

Acute dermatitis was significantly less common in the DART arm, although late toxicities were comparable. Secondary oncologic outcomes—including 2-year overall survival, progression-free survival, and locoregional and distant recurrence rates—showed no differences between the two approaches.

The authors concluded that while DART did not reduce one-year xerostomia, it achieved comparable tumor control and toxicity outcomes while enabling the use of substantially smaller PTV margins. These findings support the feasibility of integrating modern adaptive radiotherapy without compromising oncologic results.

 Reference (Pub-Med Link): Sher DJ, Avkshtol V, Lin MH, et al. Impact of daily adaptive head and neck radiotherapy on toxicity and quality of life: Results of the dartboard phase ii randomized trial. J Natl Cancer Inst 2025;117:2488-2494. https://doi.org/10.1093/jnci/djaf232

Key Institution: University of Texas Southwestern Medical Center

Keywords: Head and Neck

Treatment of hypopharynx and oropharynx with definitive chemoradiation is associated with adverse effects on patients’ quality of life. In this phase 3, multicenter, randomized controlled trial, the authors investigated the effects of dysphagia-optimized IMRT (DO-IMRT) which reduced the radiation dose to dysphagia- and aspiration-related structures. RT doses were 65 Gy to primary tumor and 54 Gy to high-risk clinical and nodal areas. A 50-Gy dose constraint to the pharyngeal constrictors outside of the high-dose target region was applied. MD Anderson Dysphagia inventory (MDADI) composite scores 12 months after RT showed better function the DO-IMRT group compared to standard IMRT group (mean scores 77.7 vs 70.6, p=0.037). Grade 3+ hearing impairment was similar in the two groups, but there was more G3+ dry mouth and dysphagia findings in the standard IMRT group vs DO-IMRT group (15% vs 5%, respectively). The authors conclude, “DO-IMRT should be considered a new standard of care for patients receiving radiotherapy for pharyngeal cancers.”

Reference (Pub-Med Link): Nutting C, Finneran L, Roe J, et al. Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (dars): A phase 3, multicentre, randomised, controlled trial. The Lancet Oncology 2023;24:868-880. https://doi.org/10.1016/s1470-2045(23)00265-6

Key Institution: The Royal Marsden Hospital, Multi-institutional

Keywords: Head and Neck Cancer

Although the risk for xerostomia has improved with use of intensity-modulated radiation therapy (IMRT), it remains one of the most common side effects after irradiation of nasopharyngeal carcinoma, mainly due to the close proximity of level II cervical lymph nodes to the parotid gland. This randomized phase 2 trial examined whether sparing of the superficial lobe of the parotid reduces xerostomia in patients receiving radiation for nasopharyngeal carcinoma.

Eighty-two patients were included for xerostomia analysis and randomized to receive either superficial parotid lobe–sparing intensity-modulated radiation therapy (SPLS-IMRT) or conventional IMRT. For all patients, the whole parotid including deep and superficial lobes was contoured and the optimization objective was V36Gy <40%. In the experimental arm, the objective for the superficial lobe was lower with V26Gy <30%.

At 12 months, the rate of xerostomia was significantly lower in the superficial lobe sparing arm (83.4% v 95%). Grade 3 xerostomia decreased from 12.5% to 0%. There were no differences in disease-free or overall survival between the arms. The study shows that sparing the superficial parotid lobe is a potential way to reduce xerostomia while maintaining target volume coverage for nasopharyngeal carcinoma.

Reference (Pub-Med Link): Huang, H., Miao, J., Xiao, X., et al. (2022). Impact on xerostomia for nasopharyngeal carcinoma patients treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT): A prospective phase II randomized controlled study. Radiotherapy and Oncology : Journal of the European Society for Therapeutic  Radiology and Oncology, 175, 1–9. https://doi.org/10.1016/j.radonc.2022.07.006

Key Institution: Sun Yat-sen University Cancer Center
Keywords: Head & Neck

Concurrent radio-chemotherapy is effective for head and neck cancer, but also has a lot of side effects. Therefore, there is some effort to de-escalate therapy for different sub-types. Patients with low risk nasopharyngeal cancer have excellent treatment outcomes and could potentially benefit from treatment de-intensification.

This randomized, phase 3, multicenter trial aimed to examine if radiation alone (RT) has non-inferior failure-free survival compared to chemoradiation (CRT) for endemic nasopharyngeal carcinoma. 341 patients were enrolled, who had cT2N0-1 or cT3N0 squamous cell carcinoma of the nasopharynx that was considered low-risk based on the following criteria: all nodes <3cm, no level IV or VB metastases, no ENE, and an EBV DNA titer <4000 copies/mL. Radiation in both arms was delivered using IMRT with 4 different dose levels including a prescribed dose of 68-70 Gy in 30-33 fractions to the primary lesion. Patients in the chemoradiation arm received 100 mg/m2 cisplatin every 3 weeks for 3 cycles.

After 46 months median follow-up, the rate of locoregional failure was 7.6% with radiation therapy alone and 6.5% with chemoradiation, and the rate of distant metastasis was 4.7% v 2.4%. The 3-year failure free survival was deemed non-inferior with radiation therapy alone compared with chemoradiation (90.5% v 91.9%). There was no difference in overall survival between radiation therapy alone and chemoradiation (98.2% v 98.6%). Quality of life outcomes were significantly better with radiation alone. The overall rate of grade 3-4 toxicity with radiation therapy alone was less than half that of concurrent chemoradiation (17% v 46%). These included lower rates of hematologic toxicity as well as less nausea/vomiting (1% v 15%), weight loss (1% v 5%), and mucositis (10% v 19%). The authors found no difference in late grade 3-4 toxicity.

In summary, early results of this trial indicate that omission of chemotherapy for early stage, low-risk nasopharyngeal carcinoma has similar 3-year failure free survival as chemoradiation.

(Open Access)

Reference (Pub-Med Link): Tang, L.-L., Guo, R., Zhang, N., et al. (2022). Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial. JAMA, 328(8), 728–736. https://doi.org/10.1001/jama.2022.13997

Key Institution: Multi-Center, China
Keywords: Head & Neck

In head and neck cancer, especially in elderly patients who are not candidates for concurrent chemotherapy there is renewed interest in hypofractionated radiation therapy, however there is limited data and lack of consensus to support its use. Additionally, swallowing outcomes for patients treated with radiotherapy alone are poorly described compared with those treated with chemo-radiotherapy, largely because they represent a group under-represented in clinical trials.

This multi-center retrospective observational study in UK compared long term swallowing function as well as outcomes (i.e., LRC and OS) between patients treated with curative intent mild hypofractionation (65-66 Gy in 30 fx over 6 weeks) and standard fractionation (70 Gy in 35 fx over 7 weeks) radiation alone for locally-advanced oropharyngeal squamous cell carcinoma (OPSCC). Swallowing function was assessed using MD Anderson Dysphagia Inventory (MDADI) questionnaire, which was sent to patients alive and cancer-free at a minimum of 2 years post-radiotherapy (n = 151, 65%).

LRC and OS were similar across schedules (p = 0.78 and 0.95 respectively, log-rank test). Enteral feeding rates during radiotherapy appeared higher in the 7-week group though this did not reach statistical significance (59% vs 48%, p = 0.08). Feeding rates were similar at 1 year post radiotherapy for both groups (10% vs 6%, p = 0.27). 107 patients returned MDADI questionnaires (71%); there were no differences between the 6- and 7-week groups for median global (60.0 vs 60.0, p = 0.99) and composite (65.8 vs 64.2, p = 0.44) MDADI scores.

This observational study of patients with oropharyngeal cancer who were treated with radiation therapy only, suggests that treatment outcomes and long-term swallowing function after mild hypofractionation over six weeks are comparable to standard fractionation over seven weeks

Reference (Pub-Med Link): Price, J. M., West, C. M., Dixon, L. M., et al.  (2022). Similar long-term swallowing outcomes for accelerated, mildly-hypofractionated radiotherapy compared to conventional fractionation in oropharyngeal cancer: A multi-centre study. Radiotherapy and Oncology, 172, 111–117. https://doi.org/10.1016/j.radonc.2022.05.013