Simultaneous Integrated Boost in Carbon Ion Radiotherapy for Head and Neck Adenoid Cystic Carcinoma

Study Overview
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Brief Summary
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The investigators aim at investigating in a prospective clinical trial whether using a Simoultaneous Integrated Boost of carbon ions treatment planning approach, improving the tumor dose conformation while lowering the unintended dose to the low-risk volume, can significantly reduce the probability of toxicity without affecting Local Control.

Detailed Description
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In photon radiotherapy, Simultaneous integrated boost (SIB)-intensity-modulated radiation therapy (IMRT) with slight hypofractionation in the HR-CTV is the current standard of care, being previously largely adopted in clinical practice and within several prospective clinical trials, with similar results in terms of toxicity and oncologic outcome. Up to now, a simultaneous integrated boost (SIB) approach has not been fully exploited in CIRT so far. The expected benefit of a SIB planning approach in carbon ion treatment is the reduction of toxicity with respect to the sequential (SEQ) approach currently used in CNAO clinical practice, while maintaining the same local control rate. This benefit depends on the potentiality of SIB to better spare normal tissues, further enhancing the intrinsic favourable physical and radiobiological characteristics of the carbon ions.

Official Title
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Simultaneous Integrated Boost (SIB) Planning Approach in Carbon Ion Radiotherapy for Head and Neck Adenoid Cystic Carcinoma

Conditions
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Carcinoma, Adenoid Cystic, Head and Neck Cancer

Intervention / Treatment
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* Radiation: simultaneous integrated boost of carbon ions radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-proven primary head and neck ACC; Unresectable stage or residual macroscopic disease after surgery or multiple microscopic margins after surgery; Patient with resectable tumor but refusing surgery cN0/pN0 - cN1/pN1 patients (only ipsilateral neck levels I and II) Absence of distant metastases or oligometastatic status (patients with ≤ 3 metastatic lung or bone lesions, excluding other sites; No previous radiotherapy in head and neck region; Karnofsky Performance Status ≥ 70; Age ≥ 18 years; Written informed consent Patients' ability to understand the characteristics and consequences of the clinical trial. Exclusion Criteria: Local conditions contraindicating CIRT (e.g., active infection or previous history of recurrent infections in or close to the tumor site; intratumoral necrosis in strict proximity of vessels; pre-existing skin, bone or soft tissue fistula; extended mucosal involvement by the tumor; previous surgery with flap reconstruction); Tumour site in nasopharynx, pharynx and tongue base (where an exclusive CIRT treatment could be at high risk of toxicity); Tumor disease involving ≥ 50% of the palate with consequent high risks of serious anatomical damage in case of significant and rapid disease response to CIRT Nodal involvement > cN1/pN1 or cN1/pN1 outside ipsilateral levels I and II Tumor surrounding carotid artery > 180° or infiltrating the vessels itanium surgical implants or metal prostheses or any other condition that prevents adequate imaging to identify the target volume and may determine uncertainties in CIRT dose distribution during treatment planning Presence of any comorbidity deemed to impact on treatment toxicity; Psychic or other disorders that may prevent informed consent Active autoimmune disease (e.g. systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis) Contraindication to MRI Pregnancy or breastfeeding in progress

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: The patients will be prospectively enrolled and treated at the sponsor's premises. Only one group of subjects will enter the phase II trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carbon ion radiotherapy<br>simultaneous integrated boost with carbon ion radiotherapy | Radiation: simultaneous integrated boost of carbon ions radiation therapy<br>* CIRT Treatment will be delivered in 16 fractions, 4 fractions per week. Treatment plans will be calculated with a Simultaneous Integrated Boost Approach (SIB). The HR-CTV will receive a total dose of 65.6 GyRBE (4.1 GyRBE/fraction). The LR-CTV will simultaneously receive a total dose of 54.4 GyRBE (3.4 GyRBE/fraction) or 48 GyRBE (3 GyRBE/fraction) at discretion of Radiation Oncologist depending on the prognostic factors (54.4 GyRBE in case of macroscopical perineural invasion or positive margin along the nerve, 48.0 Gy(RBE) in case of elective perineural irradiation or microscopic focal intratumor perineural invasion).<br>* Other names: CIRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute and sub acute toxicity as assessed by CTACE 5.0 | Acute and subacute toxicity will be assessed with clinical evaluation within 180 days after the end of treatment and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | 90 and 180 days after radiation treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local control assessed through head and neck MRI | LC is expected to be the same as in the sequential traditional approach | from last day of radiation treatment up to 12 months until disease progression or death or last follow up up to 5 years | 
| toxicity evaluation | various toxicity endpoints will be aggregated and analysed to build predictive factors to build multivariate predictive models | toxicity assessed at 90, 120, 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenoid cystic carcinoma, hadrontherapy, carbon ion radiation therapy CIRT, head and neck cancer, SIB