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

Not Applicable
Conditions
Non-Small Cell Lung Cancer
Interventions
Radiation: Radiotherapy Group
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.

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
Arm && Interventions
GroupInterventionDescription
Radiotherapy GroupRadiotherapy GroupPatients with LA NSCLC treated with concurrent chemoradiation will be enrolled. During treatment all patients will undergo weekly chest CT simulations without intravenous contrast to assess acute toxicity and tumor shrinkage, and they will be all visualized by two radiation oncologists independently. For all CT simulations, each physician will be able to judge whether reduction will be (1) present and clinically significant, (2) present and clinically non significant, or (3) absent. In the case of physician agreement for the first category, a contrast-enhanced CT will be performed to better visualize node reduction, a new target volume will be delineated, and a new treatment plan (replanning study) performed. Patients will be treated without any time break.
Primary Outcome Measures
NameTimeMethod
Incidence of Local Recurrence and Pattern of Failurethree 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
NameTimeMethod
Progression-Free Survivalthree 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 Survivalthree 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 evaluationthree 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

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