Omitting Clinical Target Volume of Unresectable Stage III Non-small-cell Lung Cancer.

Omitting Clinical Target Volume Under PET-CT Guidance in Unresectable Stage III Non-small-cell Lung Cancer.

About 20-30% of patients with stage III non-small cell lung cancer (NSCLC) are unresectable and definitive concurrent radiochemotherapy is the standard care. Intensity-modulated radiation therapy (IMRT) is a new radiotherapy technology, including gross tumor volume (GTV), clinical target volume (CTV), internal target volume (ITV), and planning target volume (PTV) as delineated target volumes. The treatment failure of local advanced NSCLC is mainly caused by local recurrence accounted for 50% and distant metastasis accounted for 50%. Local recurrence occurs both within the radiation field and outside the radiation field. Elective nodal irradiation (ENI) was designed before, however the adverse events (AEs) was not satisfactory. Afterwards, involved field radiotherapy (IFRT) showed that a reduced irradiation field did not increase local recurrence, and lowered the AEs Thus, IFRT has been broadly used in clinical work instead of ENI. IFRT still has disadvantages, including the risk of radiation respiratory events and radiation esophagitis, can the irradiation area be further reduced to reduce adverse reactions without affecting the efficacy? Positron emission tomography -computed tomography (PET-CT) can accurately assess primary tumor and metastatic lymph nodes in NSCLC patients better than CT . A meta-analysis of 39 clinical studies showed that the median sensitivity and specificity of PET-CT for the detection of lymph node involvement were 85% and 90%, respectively, while those of CT alone were only 61% and 79%, respectively. The radiotherapy application of PET-CT in image acquisition can ensure the delineation of both primary tumor and mediastinal lymph node metastasis. Under this condition, can the radiation field be further reduced to lower the dose to normal tissue and radiotherapy-associated AEs? A dosimetry study showed that when a dose of 60 Gy was given to the primary tumor and positive mediastinal lymph nodes, even if the CTV was omitted, a dose of 50 Gy was sufficient to cover the subclinical area.

Study Overview

• Status: Completed
• Conditions: Stage III Non-small-cell Lung Cancer
• Intervention / Treatment: Radiation: The enrollment was randomly (1:1) assigned into the study group with CTV-omitted IMRT under PET-CT guidance and the control group with CTV-delineated IMRT using a random number table.

Detailed Description

A dosimetry study showed that when a dose of 60 Gy was given to the primary tumor and positive mediastinal lymph nodes, even if the CTV was omitted, a dose of 50 Gy was sufficient to cover the subclinical area.

• Study Type: Observational
• Enrollment (Actual): 90

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with advanced (Stage IIIa or IIIb) NSCLC that was histologically or cytologically inoperable.

Description

Inclusion Criteria:

• Patients with advanced (Stage IIIA or IIIB AJCC 7) NSCLC that was histologically or cytologically inoperable
• ECOG whole body status (performancestatus,PS) level 0 or 1
• The estimated survival time is more than 12 weeks, 18 ~75 years old
• Laboratory results within 2 weeks prior to radiotherapy met the following criteria: ① Neutrophil count > 1,500/ MCL Heathko-Pilot Oncology Research Fund; ② Platelet > 50,000/ MCL; ③ Total bilirubin < 1.5 times of the normal upper limit value; ④AST(SGOT)/ALT(SGPT) < 2.5 times of the normal upper limit; ⑤ Serum creatinine < 1.5 times of the normal upper limit value; ⑥ The results of coagulation function examination were within the normal range
• Women of childbearing age must have taken reliable contraceptive measures or conducted pregnancy tests (serum or urine) within 7 days before admission, and the results are negative, and are willing to use appropriate methods of contraception during the trial period and 8 weeks after the last administration of the trial drug. For men, they must agree to use appropriate methods of contraception or surgical sterilization during the trial period and 8 weeks after the last administration of the trial drug
• Understand and voluntarily sign written informed consent
• The investigator judged that the patient had good compliance

Exclusion Criteria:

• Malignant pleural/pericardial effusions, previous thoracic radiotherapy or chemotherapy
• Uncontrolled concurrent diseases, including but not limited to symptomatic congestive heart failure, unstable angina pectoris and myocardial infarction, uncontrolled grade III hypertension, liver insufficiency, renal insufficiency, uncontrolled diabetic blood sugar, arrhythmia, mental illness or social condition, etc.
• Pregnant or nursing women
• The patient has no history of intracranial hemorrhage or spinal cord hemorrhage
• HIV-positive patients receiving combination antiretroviral therapy
• Active tuberculosis
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Prior allogeneic stem cell or solid organ transplantation
• Researchers determine other conditions that may affect the conduct of clinical studies and the determination of their findings

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
study group; CTV-omitted IMRT under PET-CT guidance	Radiation: The enrollment was randomly (1:1) assigned into the study group with CTV-omitted IMRT under PET-CT guidance and the control group with CTV-delineated IMRT using a random number table.
control group; CTV-delineated IMRT under PET-CT guidance	Radiation: The enrollment was randomly (1:1) assigned into the study group with CTV-omitted IMRT under PET-CT guidance and the control group with CTV-delineated IMRT using a random number table.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of radiation respiratory events or esophagitis with grade 3 or higher	incidence of radiation respiratory events or esophagitis with grade 3 or higher	after radiation therapy，up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival		through study completion, an average of 2 year
objective response rate	objective response rate	through study completion，up to 12 weeks
locate control rate		through study completion，up to 12 weeks
progression-free survival		through study completion，up to 12 weeks

Collaborators and Investigators

• Sponsor: Jianguo Sun

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: April 9, 2022
• First Posted (Actual): April 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 30, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: NSCLC; IMRT; PET-CT
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: XQonc-018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No