Adaptive Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer (LARTIA Trial)

Not Applicable

• Conditions: Non-Small Cell Lung Cancer

• Registration Number: NCT03583723
• Lead Sponsor: Campus Bio-Medico University

Brief Summary

Anatomical change of tumor during radiotherapy contributes to target missing. However, in the case of tumor shrinkage, adaptation of volume could result in an increased incidence of recurrence in the area of target reduction. This study aims to investigate the incidence of failure of the adaptive approach in Locally Advanced Non-Small Cell Lung Cancer and, in particular, the risk for local recurrence in the area excluded after replanning.

Detailed Description

Concurrent chemoradiation is the standard of care for patients affected by locally advanced (LA) NSCLC. Its superiority over radiotherapy alone or sequential chemoradiation has been proved in multiple phase III randomized trials. In a meta-analysis of six randomized studies, concurrent chemoradiotherapy decreased locoregional progression by 6.1% at 5 years when compared with sequential chemoradiation. This resulted in an improvement in overall survival of 4.5% at 5 years that was possibly directly related to locoregional control. Many patients however succumb to locoregional failure or distant metastases. Thanks to modern radiotherapy techniques, some strategies manage the geometrical uncertainties of imaging, treatment planning, and treatment delivery and thereby improve target coverage with a much steeper dose gradient and less irradiated normal tissue. The introduction of image-guided radiotherapy reveals the occurrence of target changes during treatment, and although the percentage of patients who experienced regression is not high (range 25%-40%), the degree of regression is in the range of 29% to 40%, corresponding to a rate of tumor shrinkage per fraction of 0.79% to 1.65%. Anatomical changes during radiotherapy might introduce discrepancies between the planned and delivered dose. Currently, the literature reports only dosimetric experiences and lacks clinical data on outcome when patients are treated with the adaptive approach. This study aims to investigate the failure pattern in patients with LA NSCLC treated with concurrent chemoradiotherapy with an adaptive approach, in particular, to evaluate the risk for local recurrence in the area excluded during replanning.

Study Timeline

• Study Start: 2012-11-02
• Primary Completion: 2017-01-10
• Study First Submitted: 2018-06-27
• Study First Submitted QC: 2018-06-27
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-10
• Study First Posted: 2018-07-11
• Last Update Posted: 2018-07-12
• Study Completion: 2019-01-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• histologically or cytologically proven NSCLC;
• inoperable stage IIIA/IIIB disease and intrathoracic relapse after surgery;
• positron emission tomography (PET)/computed tomography (CT) and/or total-body CT with contrast excluding metastatic disease (including brain);
• no previous radiotherapy treatment;
• Eastern Cooperative Oncology Group performance status of 0 to 1;
• clinically measurable/evaluable disease;
• minimum life expectancy of 12 weeks;
• adequate respiratory, renal, hepatic and bone marrow function and non-contraindicative cardiovascular disease.

Exclusion Criteria

• previous radiotherapy treatment
• concurrent systemic disorders incompatible with chemotherapy or radiotherapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Incidence of Local Recurrence and Pattern of Failure	three months	Patients are not considered to have local-regional control unless they achieve at least a partial response of their primary tumor or stable disease by imaging. Patients who do not achieve objective response are considered to have local-regional failure. Local-regional control rates are analyzed using the Kaplan-Meier method. Local recurrences are defined according to a dimensional and metabolic increase at chest CT with intravenous contrast and fludeoxyglucose F 18 (FDG) PET/CT. Recurrences are identified visually and independently by three radiation oncologists with the same method. The modality for definition of failures is readjusted with these definitions: "in-field failure" when a dimensional and/or metabolic progression is reported within the replanning PTV; "marginal failure" in cases of recurrence in the initial PTV but not in the replanning PTV, and "out-of-field failure" if the recurrence occurs outside the initial PTV.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival	three years	Progression-free survival is obtained from the beginning of treatment to the observation of progression/recurrence, or to the last follow-up if no event is observed.
Overall Survival	three years	Overall Survival is determined from the day of the diagnosis to the death, or to the last follow-up if no event is observed
Response evaluation	three months	Response evaluation is defined according to the Response Evaluation Criteria in Solid Tumors criteria for complete and partial response, progression, and stable disease.

Trial Locations

Locations (1)

Michele Fiore; 🇮🇹 Rome, Italy