Lung Function After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer, Changes and Predictive Markers

Abstract

IntroductionThe present study explores changes in pulmonary function, symptoms and radiological signs of pneumonitis after curatively intended stereotactic body radiation therapy (SBRT).MethodsAll inoperable, early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy (SBRT) from 2014-2017 were included in this single-centre study. They were followed regularly for 12 months after treatment. The patients were classified into three groups based on radiology and symptomatology: no radiation pneumonitis, asymptomatic and symptomatic radiation pneumonitis.ResultsForty-four patients with stage IA-IIB disease were treated with 45–56 Gy in 3–8 fractions. The median age was 75 years, 43% of the patients were female; 60% of the patients had a COPD in GOLD grade of 2-4, and 95.5% were active or former smokers. Symptomatic radiation pneumonitis occurred in 18% of the patients and asymptomatic pneumonitis as defined by radiology, in 39%. The mean of forced expiratory volume in 1 second (FEV1) and diffusion capacity for carbon monoxide (DLCO) decreases for all patients during the first years were higher than one would expect from physiologic ageing. FEV1 and DLCO in percent decrease 7-8% at 1-1.5 months in the symptomatic radiation pneumonitis group. CT scan findings consistent with radiation pneumonitis occurred after a median of 2.9 months in the symptomatic and 5.4 months in the asymptomatic radiation pneumonitis groups. In the group with symptomatic radiation pneumonitis, symptoms, as measured by the Clinical COPD questionnaire score, significantly increased at 3 and 6 months. Significant higher maximum doses to the critical lung volumes DC1000cm3 (1000 cm3 of lung receiving a given dose or less) and DC 1500cm3 (1500 cm3 of lung receiving a given dose or less) were observed in patients who developed radiation pneumonitis.ConclusionEarly decrease in measured FEV1 and DLCO occurred before imaging changes and symptoms and might indicate the development of symptomatic radiation pneumonitis. The dose to critical lung volumes of DC1000 cm3 and DC1500 cm3 may predict the risk for the development of symptomatic radiation pneumonitis.

Circulating T Cell Activation and Exhaustion Markers Are Associated With Radiation Pneumonitis and Poor Survival in Non-Small-Cell Lung Cancer

“…While T cell exhaustion is mostly used in relation to chronic infections, we speculate that the enhanced early levels of sTIM-3 (i.e., within 3 months) in the CCRT group, without enhanced sCD25 levels, could reflect the effects of more acute RP, which is seen 1-3 months after CCRT (43)(44)(45)(46), as a mechanism to prevent persistent and overshooting T cell activation. The more gradual increases in sTIM-3, sCD25 and CCL21 within the SBRT group correlate with the later onset of RP in this group occurring after 5-10 months (9)(10)(11)(47)(48)(49). Although PD-1, another T cell exhaustion marker, was not significantly associated with RP, the temporal trajectory was similar to sTIM-3 in the SBRT group but not in the CCRT group, possibly reflecting some different effects on T cell subsets of these radiation modalities.…”

“…A total of 66 patients were included in the study. Changes in pulmonary function, symptoms, and radiological signs of RP after SBRT have previously been studied in 44 of these patients ( 10 ).…”

“…The risk of developing radiation-induced lung injury limits effective highdose thoracic radiation therapy for early-stage and locally advanced NSCLC patients (5) (5). The reported incidence of radiation pneumonitis (RP) after SBRT for NSCLC varies from 2% to 47% (6)(7)(8)(9)(10)(11), and the incidence after CCRT varies from 5% to 40% (12)(13)(14)(15)(16)(17).…”

Clinical Outcomes Following Proton and Photon Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer

“…In the current study, the patients who were known to have a high risk of radiation pneumonitis, or as having poor baseline PFT results or multiple comorbidities (especially ILD) [ 27 , 28 ], underwent proton SBRT more frequently than photon SBRT. The incidences of radiation pneumonitis, however, were not different following either modality.…”

Radiation-Induced Dyspnea in Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

“…The increasing use of hypo-fractionated treatments delivered by SBRT implies high doses per fraction, larger than 10 Gy and up to 20-30 Gy [6,7], claiming the need for dedicated normal tissue complicated probability (NTCP) models for RILD [4]. A range of clinical and dosimetric parameters have previously been shown to be predictive of RILD after lung tumors hypo-fractionated RT in several studies [8][9][10][11][12][13][14] though producing conflicting results [15]. Furthermore, with SBRT being increasingly used in NSCLC elderly patients with significant comorbidities [16], there is growing attention to those symptoms impacting on QoL after treatment, including symptoms related to lung disease as dyspnea [17][18][19].…”