Clinical trial NCT02089204: Hypoxia Imaging -Guided Radiotherapy of Nasopharyngeal Carcinoma
Official title: Clinical Feasibility Study of Hypoxia Imaging -Guided IMRT on the Individualized Radiotherapy of Nasopharyngeal Carcinoma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Nasopharyngeal Carcinoma
Keywords: Hypoxia Imaging -Guided Radiotherapy
PET/CT
simultaneous modulated accelerated radiation therapy (SMART)
Lead sponsor: Xuzhou Medical University
Sponsor class: OTHER
Collaborators: name: University of North Carolina, Chapel Hill
First posted: 2014-03-17
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Between June 2010 to June 2015, patients from Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical College.

Brief summary: Nasopharyngeal carcinoma (NPC) differs from other head and neck malignancies in terms of its epidemiology, pathology, and treatment outcome . It is endemic in China and is one of the major public health problems. Concurrent radiotherapy and chemotherapy is the primary treatment for patients with NPC. Despite such aggressive treatment, many patients with locally advanced NPC still develop locally recurrent disease. Since local control is directly related to patient morbidity and mortality in NPC, there is a strong need to identify methods to further improve treatment outcome for NPC.

One strategy to improve local control is to escalate the dose of radiotherapy. This is because local control has been shown to be directly related to the radiotherapy dose. Several different techniques, including brachytherapy, stereotactic radiosurgery, and dose-painting intensity modulated radiotherapy (IMRT), have been used to increase radiotherapy dose. However, due to the large number of critical anatomic structures near the nasopharynx, dose-escalation in NPC can also lead to increased toxicities. One technique that has achieved dose-escalation with minimal increase in toxicity is simultaneous modulated accelerated radiation therapy (SMART). The main challenge for such treatment is to identify the appropriate tumor volume to receive the high-dose radiotherapy. Conventional dose-escalation is conducted using computed tomography (CT) to identify the gross tumor volume (GTV). However, recent progress with F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in treatment planning allows more accurate tumor volume delineation. We hypothesize that the use of PET/CT in treatment planning can improve dose-escalation radiotherapy for NPC which in turn can improve therapeutic efficacy while reducing toxicity. PET/CT imaging of tissue hypoxia using \[F-18\]fluoromisonidazole (FMISO), the most widely used nitroimidazole imaging agent.Given that there has been no clinical trials directly comparing conventional chemoradiotherapy to CT-guided dose-escalation chemoradiotherapy or PET/CT guided dose-escalation chemoradiotherapy in locally advanced NPC.This was a study to evaluate the role of FMISO-PET hypoxia imaging for predicting survival in NPC,our study aims to compare the local control, overall survival and toxicities of the three treatment regimens..

Detailed description: Study Design Patients with previously untreated Stages III\~IVA (AJCC 6th Edition) of locally advanced NPC, Karnofsky performance status≥70, and good bone marrow, liver and kidney functions (white blood count ≥ 4.0×109/L, platelets ≥ 100×109/L, albumin ≥30 g/L , creatinine ≤100μmol/L) were enrolled on this study. Patients younger than 18, those with a prior (within 5 years) or synchronous malignancy were excluded. Pretreatment evaluations consisted of a history and physical, dental and laboratory studies. The clinical stage was determined based on all information provided by examinations including contrast enhanced CT and magnetic resonance imaging (MRI) of head and neck, Chest X-ray, liver sonography, bone scan, and 18F-FDG-PET. All tumors were histologically confirmed except those of distant sites.

Patients who met the eligibility criteria were randomized 1:1:1 into the three treatment arms: conventional chemoradiotherapy (group A), FDG PET/CT -guided dose escalation chemoradiotherapy (group B) and FMISO PET/CT -guided dose escalation chemoradiotherapy (group C). All patients were given concurrent chemoradiotherapy within two weeks of diagnosis. Radiotherapy was delivered using the simultaneous modulated accelerated radiation therapy (SMART) IMRT technique in the dose-escalation treatment arms. Concurrent chemotherapy consisted of cisplatin (20mg / m2 ,iv, d1- 4) and docetaxel (75mg / m2, d1, d8) administered on the 1st and 4th week of treatment. All patients received adjuvant chemotherapy that ranged from 2 to 4 cycles.

Follow-up and statistical analysis Planned patient assessment included physical examination and fiberoptic nasopharyngoscopy every 3 months to 3 years starting at 4 weeks post-treatment. A contrast-enhanced CT or MRI of the head and neck is also obtained at each follow up. After 3 years, the patients were followed yearly thereafter. Suspected recurrences were histologically proven. To assess for distant metastasis, CT of the chest and bone scan were obtained every half a year. During every follow-up visit, treatment toxicity were assessed. Radiotherapy-related toxicities were graded according to the Acute and the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Chemotherapy-related toxicities (except nausea or alopecia) were graded by the criteria of the WHO.

All events were measured from the date of randomization. OS was defined as the time from the date of radiotherapy to death or the latest date known to be alive. Durations were calculated from the end of treatment. The Kaplan-Meier method was used to calculate the actuarial rates of local control, DFS and OS. The χ2 test was used for comparing incidence rates and categorical variables and Student's t-test was used for comparing the means of continuous variables.

Eligibility criteria: Inclusion Criteria:

* histologically confirmed NPC by biopsy,
* no evidence of distant metastasis,
* no previous treatment for NPC,
* Stages III\~IVA (AJCC 7th Edition) of locally advanced ,
* adequate liver function (albumin ≥30 g/L),
* adequate renal function (creatinine ≤100μmol/L) ,
* adequate bone marrow function(white blood count ≥ 4.0×109/L, platelets ≥ 100×109/L),
* Karnofsky performance status≥70,

Exclusion Criteria:

* Patients younger than 18,
* those with a prior (within 5 years) or synchronous malignancy were excluded.
* presence of distant metastases,
* pregnancy or lactation,
* other concomitant malignant disease.

Primary outcomes:
measure: local progression-free (LPF) survival rates
timeFrame: 5 years
Secondary outcomes:
measure: disease-free survival (DFS)
timeFrame: 5 years
measure: overall survival (OS)
timeFrame: 5 years
Other outcomes:
measure: acute toxicities
timeFrame: from treatment start to 4 weeks post-treatment
measure: Late toxicities
timeFrame: from 4 weeks post-treatment to 5 years.
Locations:
Study officials:
affiliation: Xuzhou Medical University
name: ZHANG Longzhen, MD
role: STUDY_CHAIR
affiliation: University of North Carolina at Chapel Hill, USA
name: Wang Andrew Z., MD and PHD
role: STUDY_DIRECTOR
affiliation: Xuzhou Medical University
name: Wang Jianshe, M.M.
role: PRINCIPAL_INVESTIGATOR
affiliation: Xuzhou Medical University
name: Xin Yong, M.M.
role: PRINCIPAL_INVESTIGATOR
affiliation: Xuzhou Medical University
name: Xu Kai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Xuzhou Medical University
name: Tang Tianyou, M.M.
role: PRINCIPAL_INVESTIGATOR
affiliation: Xuzhou Medical University
name: Ding Xin, M.M.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang J, Zheng J, Tang T, Zhu F, Yao Y, Xu J, Wang AZ, Zhang L. A Randomized Pilot Trial Comparing Position Emission Tomography (PET)-Guided Dose Escalation Radiotherapy to Conventional Radiotherapy in Chemoradiotherapy Treatment of Locally Advanced Nasopharyngeal Carcinoma. PLoS One. 2015 Apr 27;10(4):e0124018. doi: 10.1371/journal.pone.0124018. eCollection 2015.