Cutaneous, Head and Neck Cancer Squamous Cell Carcinoma
Conditions
Keywords
skin, head and neck, radiation, SBRT, SABR
Brief summary
The purpose of this study is to compare the effectiveness and side effects of stereotactic radiotherapy (5 sessions) against conventional (standard) radiotherapy (20-30 sessions) for the treatment of skin cancer involving the head and neck after surgical resection. Stereotactic radiotherapy works in the same way that conventional (standard) radiotherapy does to kill cancer cells by damaging their genetic material and stopping the cancer cells from making copies of themselves. This study will help the study doctors find out if this different approach is the same, better, or worse than the standard of care for your cancer.
Detailed description
This study is a phase II randomized trial where patients will be randomized in a 1:2 ratio to standard of care treatment with conventional fractionation PORT (Arm 1) vs. ultrahypofractionated stereotactic PORT (Arm 2). Patients will be stratified by pathologic nodal status (pN1 vs. pN2-pN3) per the American Joint Committee on Cancer (AJCC) 8th edition staging and use of immunotherapy (classified as neoadjuvant immunotherapy (with or without adjuvant immunotherapy) vs. planned for adjuvant immunotherapy only vs. no immunotherapy. Patients randomized to Arm 2 will be also compared to historical control data for primary endpoint of tumor local control at 2-years. The objective of this study is to assess the clinical efficacy, toxicity and QOL of ultra-hypofractionated SABR compared to conventional fractionation for adjuvant radiation following resection of locally advanced, node-positive cutaneous SCC of the head and neck. Primary endpoint \- Tumor control within the irradiated field at 2 years following adjuvant radiation completion defined as absence of clinical, radiographic or biopsy-proven recurrence within the irradiated field Secondary endpoints * Regional recurrence * Disease-free survival (DFS) * Overall survival (OS) * Rate of salvage treatment (surgery in the ipsilateral neck) and freedom from unsalvageable recurrence in the ipsilateral parotid gland or neck * Radiation-associated toxicity based on the Common Terminology Criteria for Adverse Events(CTCAE) version 5.0 * Patient-reported outcomes using the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) and the EuroQOL 5-Dimension 5-Level (EQ-5D-5L) questionnaires
Interventions
RADIATIONSBRT
Patients will receive ultra-hypofractionated stereotactic radiation over 5 treatments delivered every other weekday or twice weekly as follows: * 40 to 42.5 Gy in 5 fractions: any areas of gross residual disease, or gross PNI on imaging * 32.5 to 35 Gy in 5 fractions: microscopic areas at risk including positive margin and/or ENE * 30 Gy in 5 fractions: entire operative bed including areas of primary tumor and involved nodes and dissected cervical nodal levels * 27.5 to 30 Gy 5 fractions: at risk undissected cervical nodal levels adjacent to pathologically involved nodal levels, based on the discretion of the treating oncologist
RADIATIONStandard Radiation
Patients will receive daily conventional fractionation radiation over 4 or 6-6.5 weeks based on the treating oncologist's discretion. The below dose levels are recommended in the following clinical scenarios but may be modified per institutional standards: 20-fraction regimen or 30 to 33-fraction regimen
Sponsors
David Palma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Patient able to provide informed consent * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Patient is a candidate for curative intent treatment * Patient is able to comprehend English adequately to complete patient reported outcome questionnaires * Biopsy-confirmed cutaneous SCC * Definitive resection of a primary cutaneous tumor within the head and neck * Tumor stage T1-T4 (AJCC 8th edition); or tumor stage unknown (T0/Tx) with a positive intraparotid, peri-parotid or cervical node that is assumed to be from a head and neck cutaneous SCC by the treating oncologist * Nodal stage N1-N3 (AJCC 8th edition) * At least 1 indication for adjuvant radiation, including: * T3 or T4 tumor stage * Lymphovascular invasion (LVI) * Perineural invasion (PNI) * Positive or close (≤ 3 mm) margin * ≥ 1 positive intraparotid, peri-parotid or cervical lymph node * Multiple local recurrences or multi-focal disease * Neoadjuvant or adjuvant immunotherapy is allowed
Exclusion criteria
* Definite metastatic disease at diagnosis * Pregnant or breastfeeding women * Significant health conditions or contraindications to receiving surgery and radiation * History of previous head and neck cancer within 5 years, except for localized skin cancers (i.e. no nodal or distant spread) * Prior head and neck radiation involving the ipsilateral parotid or neck. However, prior radiation to the index skin cancer that has led to the parotid nodal disease being treated on this trial is allowed, as long as there is no overlap, or inconsequential overlap, in the judgement of the treating oncologist. * Indications for contralateral neck radiation (i.e. contralateral or bilateral lymph nodes) * Previous invasive malignancy within 5 years, unless controlled with no evidence of disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor control | 2 years | Tumor control within the irradiated field at 2 years following adjuvant radiation completion defined as absence of clinical, radiographic or biopsy-proven recurrence within the irradiated field |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival (DFS) | 2 years | calculated as time from randomization to evidence of recurrence at any site, death from any cause, or last follow-up, whichever occurs first. New primary cutaneous SCC of the head or neck will not be counted towards DFS events. |
| Overall survival | 2 years | calculated as time from randomization to death from any cause, or last follow-up, whichever occurs first. |
| Rate of salvage surgery | 2 years | calculated as time from randomization to salvage surgery in the ipsilateral treated neck. Freedom from unsalvageable parotid/neck recurrence will be documented as time from randomization to evidence of recurrence in the ipsilateral parotid gland or neck that cannot be salvaged (either surgery or radiation), or last follow-up, whichever occurs first. |
| Regional recurrence | 2 years | calculated as time from randomization to evidence of disease recurrence anywhere in the ipsilateral parotid gland or neck |
| Patient-reported outcomes | Baseline, 3, 6, 12, 18, 24 months post-treatment and yearly from years 2-5 after the end of radiation. | Patient-reported outcomes using the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) questionaries. The head and neck cancer specific symptoms are rated on a 0-10 scale to indicate the presence and severity of the symptoms. Lower scores represent better functioning and quality of life. |
| Patient Reported Outcome | Baseline, 3, 6, 12, 18, 24 months post-treatment and yearly from years 2-5 after the end of radiation. | Patient reported outcome using the Euro QOL 5-Dimension 5-Level (EQ-5D-5L) questionnaire. EQ-5D-5L is a widely used questionnaire for measuring health-related quality of life, assessing five key health areas (Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression) with five levels of severity (no to extreme problems) and a self-rated health scale (EQ-VAS) for overall well-being, helping evaluate treatments and health interventions. |
| Radiation-associated toxicity | Baseline, during treatment, 2 weeks post treatment, 4 weeks post treatment, 3, 12, 18, 24 months post treatment, and yearly from years 2-5 after the end of radiation. | Radiation-associated toxicity based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, grade 2 or higher. |
Countries
Canada
Contacts
Primary ContactPalma
Outcome results
None listed