QUAD SHOT regimen for palliative treatment in head and neck squamous cell carcinoma: a systematic review and meta-analysis

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, particularly in recurrent or metastatic settings. Conventional radiotherapy may cause substantial toxicity, especially in previously irradiated or heavily pretreated patients. The hypofractionated QUAD SHOT regimen has demonstrated palliative activity, but its efficacy, symptom palliation, quality-of-life (QoL) outcomes, and safety have not been comprehensively quantified. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a protocol prospectively registered in PROSPERO (CRD420251119819), we searched PubMed, Embase, and the Cochrane Library for randomized controlled, prospective single-arm, and retrospective studies evaluating QUAD SHOT in HNSCC. Studies enrolling at least ten patients and reporting eligible efficacy or safety outcomes were included. The primary outcome was objective response rate (ORR). Secondary outcomes included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs). Symptom relief and formal QoL outcomes were evaluated in a post hoc extension of the original analysis. Pooled estimates were calculated using random-effects models. Twelve studies involving 764 patients were included. The pooled ORR was 58% (95% CI, 45%–69%), with substantial heterogeneity, and the pooled DCR was 84% (95% CI, 80%–88%), with low heterogeneity. The pooled median PFS and OS were 4.46 months (95% CI, 3.09–6.44) and 6.88 months (95% CI, 5.19–9.14), respectively. The pooled proportions of patients experiencing relief of pain, dysphagia or odynophagia, and bleeding or haemorrhage were 64% (95% CI, 57%–71%), 64% (95% CI, 41%–82%), and 79% (95% CI, 64%–88%), respectively. Formal QoL outcomes were reported in only two studies and were summarized descriptively because of incompatible reporting formats. Grade ≥ 3 mucositis and dermatitis occurred in 2% (95% CI, 1%–4%) and 1% (95% CI, 1%–3%) of patients, respectively. Exploratory subgroup analyses according to completed treatment cycles were susceptible to treatment-continuation and selection bias and should not be interpreted causally. QUAD SHOT was associated with meaningful tumor control and symptom relief, with low incidences of severe mucositis and dermatitis. However, the evidence was derived predominantly from retrospective studies, and several analyses showed substantial heterogeneity. Prospective studies incorporating standardized symptom and QoL assessments are required to confirm these findings and optimize treatment delivery.