Quad Shot Versus Split Course Radiotherapy in Incurable Head and Neck Cancer

The optimal palliative radiotherapy regimen for incurable head and neck squamous cell carcinoma remains undefined. The standard approach at the Instituto Nacional de Cancerologia is the split-course regimen. Although effective for local symptom control, it requires a prolonged treatment course and is associated with significant acute toxicities that can compromise the comfort and quality of life of frail patients with a limited life expectancy.

The Quad Shot regimen, a hypofractionated approach initially evaluated in the RTOG 8502 trial for pelvic malignancies, offers a substantially shorter treatment duration. It has shown promising symptom control and lower toxicity profiles in retrospective and early phase studies for head and neck cancers. However, there is a lack of prospective, randomized data directly comparing the Quad Shot regimen to the split-course approach.

This is a single-center, open-label, exploratory phase II randomized controlled trial designed to compare the efficacy, safety, and tolerability of the Quad Shot regimen versus the split-course regimen. A total of 40 adult patients will be centrally randomized in a 1:1 ratio using permuted blocks of 4, stratified by tumor volume, to receive either the experimental hypofractionated regimen or the active comparator.

To ensure data quality, the study will utilize an institutional REDCap database for electronic case report forms (eCRF) with double data entry and monthly quality control checks. Quality assurance of the radiotherapy plans will be enforced through peer review and patient-specific pre-treatment dosimetry.

A formal interim analysis for safety and futility is planned once 50% of the recruitment target is reached. Final statistical analyses will follow the Intention-To-Treat (ITT) principle. Given the palliative nature of the cohort, competitive mortality will be factored into longitudinal statistical models (such as mixed-effects models) to adequately manage missing data without distorting efficacy and quality of life estimations.

Inclusion criteria

• Adult patients (>= 18 years) with a histopathological diagnosis of incurable squamous cell carcinoma of the head and neck, not candidates for curative-intent treatment.
• Metastatic or locally advanced unresectable disease, in a strictly palliative setting.
• Medical indication for palliative radiotherapy.
• Performance status: Karnofsky >= 50 or ECOG <= 3.
• Clinical capacity to receive radiotherapy in an outpatient setting.
• Estimated life expectancy greater than 3 months.
• Presence of at least one measurable lesion according to RECIST 1.1 criteria.
• Logistical capacity and willingness to adhere to follow-up clinical and radiological controls up to 6 months post-treatment.
• Signed informed consent.

Exclusion criteria

• History of previous radiotherapy to the same anatomical region to be treated.
• Diagnosis of a second active malignancy that could interfere with the evaluation of oncological outcomes.
• Presence of clinical instability or severe comorbidities that contraindicate radiotherapy treatment.
• Severe cognitive or psychiatric alterations that prevent the understanding of the nature of the study, signing the consent form, or adherence to the protocol.
• Women who are pregnant or breastfeeding