Assessing Tumor Response and IMRT Treat Plan After IC Based on FDG-PET/CT for Locally Advanced HNSCC

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety and efficacy of cisplatin plus intensity-modulated radiotherapy (IMRT) based on FDG-PET/CT after induction chemotherapy (IC) for locally advanced head and neck squamous cell carcinoma.

Detailed Description
-----------------
Current guidelines define that pre-IC target volumes must be used for radiotherapy (RT) planning. This prospective, phase II trial assessed the results of patients with locally advanced squamous cell carcinoma of head and neck treatment with IC following by chemoradiotherapy (CRT), using post-IC PET/CT images for IMRT planning.

Official Title
-----------------
Assessing Tumor Response and IMRT Treatment Planning After Induction Chemotherapy Based on FDG-PET/CT for Locally Advanced Head and Neck Squamous Cell Carcinoma.

Conditions
-----------------
Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Radiation: IMRT
* Radiation: PET/CT
* Drug: Docetaxel
* Drug: Fluorouracil
* Drug: Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients aged 18 years or over; Histologically confirmed locally advanced (stage III and IV) head and neck squamous cell carcinoma (HNSCC); Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Signed written informed consent approved by the Lithuanian Bioethics Committee (LBEC); Exclusion Criteria: Positive serum pregnancy test in women of childbearing potential or breastfeeding; Presence of distant metastasis; Second primary tumor; History of other malignancy within the last 5 years; Recurrent head and neck cancer; Serious uncontrolled concomitant disease that would contraindicate the use of any drugs use in this study as chemotherapy or radiotherapy; ; Inadequate organ function, evidenced by the following laboratory results: Absolute neutrophil count <1,500 cells/mm3; Platelet count <100,000 cells/mm3; Hemoglobin <9 g/dL; Total bilirubin greater than the upper limit of normal (ULN); AST (SGOT) or ALT (SGPT) >1,5 x ULN; Alkaline phosphatase levels >2,5 x the ULN; Serum creatinine >2,0 mg/dl or 177 umol/l.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Induction chemotherapy (Docetaxel, Cisplatin and Fluorouracil) following radiochemotherapy (IMRT using PET/CT images after IC for treatment planning + cisplatin iv 40 mg/m2 weekly). | Radiation: IMRT<br>* IMRT treatment planning using FDG-PET/CT images after induction chemotherapy (IC).<br>* Other names: intensity-modulated radiation therapy;Radiation: PET/CT<br>* Assessing tumor response using FDG-PET/CT.<br>* Other names: Positron emission tomography-computed tomography;Drug: Docetaxel<br>* 75 mg/m2, IV (in the vein) on day 1 every 3 weeks. Number of cycles: 3.<br>* Other names: Taxotere, Docefrez;Drug: Fluorouracil<br>* 750 mg/m2 continuous infusion for 120 h IV (in the vein) every 3 weeks. Number of cycles: 3.<br>* Other names: 5-Fluorouracil, Adrucil;Drug: Cisplatin<br>* 75 mg/m2, IV (in the vein) on day 1 every 3 weeks. Number of cycles: 3.<br>* Other names: Platinol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS was defined as the time from the first day of IC first cycles to either progression or death. | 24 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumour metabolic response (MTV) reduction (%) | MTV was defined as the tumor volume with FDG uptake segmented by a gradient-based method and fixed threshold methods at >40% of SUVmax. The MTV predictive value for tumor response to IC was assessed by comparing MTV's reduction (MTV of second PET/CT difference from MTV of first PET/CT in percent) in IC responders versus non responders and correlation with PFS and OS. | 2 weeks after IC | 
| Total lesion glycolysis (TLG) reduction (%) | The TLG was defined as (MTV) x (SUVmean). The TLG predictive value for tumor response to IC was assessed by comparing TLG reduction (TLG of second PET/CT difference from TLG of first PET/CT in percent) in IC responders versus non responders and correlation with PFS and OS. | 2 weeks after IC | 
| SUVmax reductions (%) | The SUVmax was defined as (tissue activity) (mcCi/ml)/(injected dose) (mCI)/(patient weight) (kg) within the voxel having the highest activity within a given region of interest (ROI). The SUVmax predictive value for tumor response to IC was assessed by comparing reductions in SUVmax (SUVmax of second PET/CT difference from SUVmax of first PET/CT in percent) in IC responders versus non responders and correlation with PFS and OS. | 2 weeks after IC | 
| Number (%) of participants with adverse events | Treatment acute toxicity during IC and CRT (chemoradiotherapy) was weekly assessed according to the National Cancer Institute Common Toxicity Criteria (NCI CTCAE) v.4.0. Late adverse events related with radiotherapy were assessed every three months after CRT using RTOG (Radiation Therapy Oncology Group) /EORTC (European Organization for Research and Treatment of Cancer) toxicity criteria. | 12 and 24 months from chemoradiotherapy | 
| Overall survival (OS) | OS was defined as the time from the first day of IC first cycles until death from any cause. | 24 months after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Head and neck cancer, PET/CT, induction chemotherapy, IMRT