Quad Shot Radiation Plus Immunotherapy Improves Local Control in Advanced Head and Neck Cancer


Quad Shot radiation plus a checkpoint inhibitor significantly improved local control vs Quad Shot alone and was well tolerated as a palliative treatment for patients with advanced head and neck cancer.

Quad Shot radiation is a hypofractionated palliative radiotherapy regimen.

Quad Shot radiation is a hypofractionated palliative radiotherapy regimen.

The combination of Quad Shot radiation therapy with immune checkpoint inhibition significantly improved local control compared with Quad Shot alone and was well tolerated in the palliative treatment of patients with advanced head and neck cancer, according to findings presented by Rituraj Upadhyay, MD, during The Radiation Oncology Summit: ACRO 2024.1

At a median follow-up of 8.8 months, local control rates at 12- and 24-months were 84.7% and 75.3%, respectively, in the combination arm (n = 40) compared with 63.3% and 43.4%, respectively in the Quad Shot–alone arm (n = 30; P = .038). Further, at 12- and 24-months the distant control rates were 56.4% and 56.4% vs 63.2% and 48.8%, respectively (P = .629).

“On multivariable analysis, concurrent immune checkpoint inhibition was a significant predictor of local control, [but] only ECOG performance status was a significant predictor of OS,” Upadhyay explained, noting a HR of 1.844 (95% CI, 1.020-3.334; P = .018). Upadhyay is a radiation oncology medical resident at the Ohio State University Comprehensive Cancer Center–James in Columbus.

Patients in the combination arm achieved a median overall survival of 9.0 months (95% CI, 6.7-11.4) vs 10.0 months (95% CI, 5.5-14.5) in the Quad Shot–alone arm, with 12- and 24-month rates of 30.0% and 21.8% with the combination vs 43.6% vs 20.3% with Quad Shot alone (P = .850). Additionally, patients achieved a best response of complete response (20.0% with the combination vs 26.7% with Quad Shot alone), partial response (50.0% vs 46.7%, respectively), stable disease (20.0% vs 16.7%), or had progressive disease (10.0% vs 10.0%), respectively.

“Patients with recurrent and metastatic head and neck cancer have limited treatment options. Although immunotherapy has emerged in a great manner for various different cancers, recent trials trying to use immunotherapy [such as the phase 1] KEYNOTE-012 study [NCT01848834] using pembrolizumab [Keytruda] alone has shown dismal response rates of [approximately] 20% in these patients,” Upadhyay explained.

Upadhyay noted that Quad Shot radiation, which is a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief as well as local control. When combined with immune checkpoint inhibitors, Quad Shot may potentiate the effects of the immune checkpoint inhibitor.

Quad Shot was administered as a total dose of 14.8 Gy over 2 days with 2 fractions per day of 3.7 Gy. Patients enrolled in the study received radiation therapy at the Ohio State University Comprehensive Cancer Center–James from 2017 to 2022. The median age was 63.3 years (range, 57.3-70.8) in the Quad Shot combination arm compared with 67.2 years (range, 59.9-80.7) in the Quad Shot–alone arm. Primary disease sites included the oropharynx (30.0% vs 36.7%), oral cavity (20.0% vs 30.0%), larynx (20.0% vs 10.0%), and cutaneous (10.0% vs 10.0%), respectively.

Additionally, patients in the combination and Quad Shot–alone arms had a P16-positive oropharynx (58.3% vs 50.0%); underwent resection for their primary disease site (42.5% vs 23.3%); received prior radiation therapy (55.0% vs 43.3%); had M1 disease (30% vs 20%); had T-stage T0/Tx (7.5% vs 10.0%), T1-2 (10.0% vs 16.7%), or T3-4 (82.5% vs 73.3%) disease; and finally, had an ECOG performance score of 0 (15.0% vs 13.3%), 1 (55.0% vs 43.3%), 2 (30.0% vs 23.3%), or 3 (0.0% vs 20.0%).

Further, most patients in the combination and Quad Shot–alone arms had a PD-L1 combined positive score of at least 1% (76.9% vs 62.5%), were former smokers (65.0% vs 50.0%), received prior systemic therapy (62.5% vs 56.7%), and received 3 Quad Shot cycles (75.0% vs 73.3%) as opposed to 4 (25.0% vs 23.3%) or 5 (0.0% vs 3.3%).

The total radiation dose was 44.4 Gy (IQR, 44.4-59.2) in both arms.

The cumulative rates of toxicities were 35.7% for grade 1, 37.1% for grade 2, and 22.9% for grade 3. Acute toxicities occurred at grades 1, 2, and 3 at the following rates: dermatitis (25.7% vs 7.1% vs 1.4%), mucositis (14.3% vs 11.4% vs 1.4%), dysphagia (8.6% vs 17.1% vs 7.1%), dysgeusia (14.3% vs 5.7% vs 1.4%), nausea/vomiting (1.4% vs 0.0% vs 0.0%), and pain (1.4% vs 2.9% vs 1.4%), respectively.

Late toxicities of xerostomia (35.7% vs 15.7% vs 1.4%), radionecrosis (0.0% vs 0.0% vs 8.6%), and fibrosis (1.4% vs 2.9% vs 0.0%), also occurred at grades 1, 2, and 3, respectively. Additionally, 1 patient experienced a grade 2 immune-related adverse effect and, overall, 23% of patients experienced grade 3 toxicities, which Upadhyay noted was similar between the 2 groups.

“Quad Shot plus [an] immune checkpoint inhibitor significantly improves local control compared with Quad Shot alone,” Upadhyay said. “This is a promising treatment option for patients with head and neck cancer unsuited for curative-intent treatment and warrants prospective evaluation.”


Upadhyay R. Palliative quadshot radiation with or without concurrent immune checkpoint inhibition for head and neck cancer.Presented at: The Radiation Oncology Summit: ACRO 2024; March 13-16, 2024; Orlando, FL.

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