Changes in Functional Lung Regions During the Course of Radiation Therapy and Their Potential Impact on Lung Dosimetry for Non-Small Cell Lung Cancer

Abstract

Purpose To study changes in functional activity on ventilation (V)/perfusion (Q) single-photon emission computed tomography (SPECT) during radiation therapy (RT) and explore the impact of such changes on lung dosimetry in patients with non-small cell lung cancer (NSCLC). Methods and Materials Fifteen NSCLC patients with centrally located tumors were enrolled. All patients were treated with definitive RT dose of ≥60 Gy. V/Q SPECTCT scans were performed prior to and after delivery of 45 Gy of fractionated RT. SPECT images were used to define temporarily dysfunctional regions of lung caused by tumor or other potentially reversible conditions as B3. The functional lung (FL) was defined on SPECT by 2 separate approaches: FL1, a threshold of 30% of the maximum uptake of the patient’s lung; and FL2, FL1 plus B3 region. The impact of changes in FL between initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. Results Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001). Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10 patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based anatomical lung had significantly lower values in FL1 than FL2, with a median reduction in the volume of lung receiving a dose of at least 20 Gy (V20) of 3%, 5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively. Conclusions Regional ventilation and perfusion function improve significantly during RT in centrally located NSCLC. Lung dosimetry values vary notably between different definitions of functional lung.

Anatomic, functional and molecular imaging in lung cancer precision radiation therapy: treatment response assessment and radiation therapy personalization

“…V/Q SPECT data indicate that ventilation and perfusion defects are greater in central then in peripheral tumors (17). Moreover, apparently normal areas of lung on CT often have impaired function as measured by V/Q SPECT (18). Importantly, regional ventilation and perfusion may improve during RT for centrally located NSCLC (18).…”

“…Moreover, apparently normal areas of lung on CT often have impaired function as measured by V/Q SPECT (18). Importantly, regional ventilation and perfusion may improve during RT for centrally located NSCLC (18). More recently, V/ Q imaging with PET tracers has become available.…”

“…This is not a limitation for the experimental proliferation tracer 18 F-fluorothymidine (FLT), where cerebral uptake is low. FLT PET/CT detected unsuspected cranial metastases in 3 of 60 patients who were enrolled in prospective studies of proliferation imaging during RT (27).…”

“…As highlighted in other articles in this issue, advances in imaging have contributed to the improved outcomes observed in lung cancer reported in recent years and new imaging modalities are becoming available with the potential to further advance the field. Rapid developments in imaging have benefited patients by increasing the accuracy of three-and four-dimensional delineation of their disease, with computed tomography (CT), magnetic resonance imaging (MRI) and most recently by positron emission tomography (PET), especially when 18 F-fluorodeoxyglucose (FDG)-PET is combined with CT in PET/ CT images. Furthermore by providing information concerning molecular or functional characteristics of tumors, it will be possible to use factors such as tumor glucose uptake, perfusion, hypoxia and proliferation to help estimate prognosis and even select systemic therapies for use in combination with radiation.…”

Functional Image-guided Radiotherapy Planning for Normal Lung Avoidance

“…Although lung function can be reduced irreversibly by radiation therapy [4,134,135], it has also been known for many years that the tumour itself can be responsible for reduced lung function [9] when bronchial obstruction and large vessel compression create regional ventilation and perfusion defects that become tempting targets for functionally-guided dose redistribution. Therefore, a potential limitation of normal lung avoidance is that lung volumes that may have received a functionally modified, amplified dose may regain some degree of function following treatment [4]; an effect noticeable on SPECT [136], PET [135], hyperpolarised gas MRI [63,137,138] and CT- [32,139] and even part way through treatment [135,140,141]. Hence, whether defects are transient [142,143], reversible [136] or persistent [134] becomes an important issue when assigning functional and non-functional planning constraints.…”