Non-Small Cell Lung Cancer
Conditions
Keywords
Adaptive radiotherapy
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.
Interventions
RADIATIONRadiotherapy Group
Patients will be immobilized with customized devices. Either four-dimensional CT or slow CT images using a multislice CT scanner will be acquired to evaluate internal target motion. Initially, gross tumor volume (GTV) will be determined in the maximum intensity projection on the initial size of the tumor and involved lymph nodal sites defined as PET-positive nodes and/or a node diameter greater than 1 cm, clinical target volume (CTV) will be defined as equal to the GTV plus node-positive stations and hilar stations, and planning target volume (PTV) will be created equal to the CTV plus a 0.5-cm safety margin. Treatment will be performed with a linear accelerator in a photon regimen, with a 6-to 15-megavolt (MV) nominal energy and three-dimensional (3D) conformal technique.
Sponsors
Campus Bio-Medico University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
Countries
Italy
Outcome results
None listed