The predictive value of 18F-FDG PET-CT for assessing the clinical outcomes in locally advanced NSCLC patients after a new induction treatment: low-dose fractionated radiotherapy with concurrent chemotherapy

Abstract

BackgroundPatients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated. Aim: to evaluate whether the early metabolic response, assessed by 18F-fluoro-deoxyglucose positron emission-computed tomography (18F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT.MethodsForty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery. 18F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis.ResultsForty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SULpeak of primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4/23 as non-responders (all non-responders at early PET-CT). Early responders had better PFS and OS than early non-responders (p ≤ 0.01). Early metabolic response was predictive factor for loco-regional, distant and global PFS (p = 0.02, p = 0.01, p = 0.005, respectively); surgery for loco-regional and global PFS (p = 0.03, p = 0.009, respectively).ConclusionsIn LA-NSCLC patients, 18F-FDG metabolic response assessed after only two cycles of IC-LDRT predicts the prognosis. The early evaluation of metabolic changes could allow to personalize therapy. This multimodality approach, including both low-dose radiotherapy that increases the effects of induction chemotherapy, and surgery that removes the disease, improved clinical outcomes. Further prospective investigation of this new induction approach is warranted.

Prognostic value of volumetric metabolic parameter changes determined by during and after radiotherapy‐based 18F‐FDG PET/CT in stage III non‐small cell lung cancer

“…Subsequently, some parameters, including SUV, MTV, and percentage changes of SUV and TLG derived from during‐RT 18 F‐FDG PET/CT, have been investigated as biomarkers for survival outcome . Furthermore, a recent study, by use of low‐dose fractionated radiotherapy concurrent to the induction chemotherapy (IC‐LDRT) instead of the standard treatment of CCRT, also observed the predictive value of early 18 F‐FDG PET/CT (ie, at the end of IC‐LDRT) in NSCLC patients …”

“…And the results showed there were no differences in pre-treatment TLG or MTV levels between stratified groups of patients, which suggests that differences in survival were attributed to the effect of treatment. It also reflects the common clinical scenarios that heterogeneous responses to a standard treatment in stage III 26 We confined our patients to stage III NSCLC because during treatment response is extraordinarily demanding in this group of patients with highly heterogeneous response to therapy and early prediction of tumor response can offer consideration of alternative approach or radiation-dose escalation to non-responding tumors. To more precisely reflect the effects of treatment, we determined the volumetric metabolic parameters, that is, MTV and TLG.…”

Predictive value of immune‐inflammation indices in metabolic response and outcome after curative radiotherapy in patients with non‐small cell lung cancer

“…A reliable tool for response evaluation is of critical importance in advanced NSCLC patients in order to select, change or intensify the treatment and individualize it. 34 In their study, Mattioli et al showed that early responders in short term PET-CT were shown to have better locoregional control, distant control, PFS and OS than early nonresponders (P ≤ .01). 34 And the authors additionally reported that their results lead to modification in planned treatment algorithm of patients concluding with a suggestion that overall survival is influenced by tailoring the treatment for the individual patient.…”

“…34 In their study, Mattioli et al showed that early responders in short term PET-CT were shown to have better locoregional control, distant control, PFS and OS than early nonresponders (P ≤ .01). 34 And the authors additionally reported that their results lead to modification in planned treatment algorithm of patients concluding with a suggestion that overall survival is influenced by tailoring the treatment for the individual patient. However, we were not able to find any significant correlation between inflammatory indices and metabolic response to RT in terms of pretreatment and posttreatment SUVmax change.…”

FDG PET/CT Imaging for Evaluation of Treatment Response in Lung Cancer

“…Mattoli ve ark. 'nın yaptığı bir çalışmada eş zamanlı düşük doz fraksiyone radyoterapi ve indüksiyon kemoterapisi uygulanan 44 hastanın tedaviye yanıtı PERCIST kriterleri ile değerlendirilmiştir (26). Bu çalışmada primer evreleme amacıyla elde edilen FDG PET/BT incelemesinde primer tümör ve metastatik lenf bezlerinde yüksek SUL peak değerleri saptanan hastalarda lokal rekürrens ve uzak metastazların daha sık gözlendiği saptanmıştır.…”