FDG and FMISO PET-guided dose escalation with intensity-modulated radiotherapy in lung cancer

Abstract

BackgroundConcomitant chemo-radiotherapy is the reference treatment for non-resectable locally-advanced Non-Small Cell Lung Cancer (NSCLC). Increasing radiotherapy total dose in the whole tumour volume has been shown to be deleterious. Functional imaging with positron emission tomography (PET/CT) offers the potential to identify smaller and biologically meaningful target volumes that could be irradiated with larger doses without compromising Organs At Risk (OAR) tolerance. This study investigated four scenarios, based on 18FDG and 18F-miso PET/CT, to delineate the target volumes and derive radiotherapy plans delivering up to 74Gy.MethodTwenty-one NSCLC patients, selected from a prospective phase II trial, had 18FDG- and 18F-miso PET/CT before the start of radiotherapy and 18FDG PET/CT during the radiotherapy (42Gy). The plans were based planned on a standard plan delivering 66 Gy (plan 1) and on three different boost strategies to deliver 74Gy total dose in pre-treatment 18FDG hotspot (70% of SUVmax) (plan 2), pre-treatment 18F-miso target (SUVmax > 1.4) (plan 3) and per-treatment 18FDG residual (40% of SUVmax). (plan 4).ResultsThe mean target volumes were 4.8 cc (± 1.1) for 18FDG hotspot, 38.9 cc (± 14.5) for 18F-miso and 36.0 cc (± 10.1) for per-treatment 18FDG. In standard plan (66 Gy), the mean dose covering 95% of the PTV (D95%) were 66.5 (± 0.33), 66.1 (± 0.32) and 66.1 (± 0.32) Gy for 18FDG hotspot, 18F-miso and per-treatment 18FDG. In scenario 2, the mean D95% was 72.5 (± 0.25) Gy in 18FDG hotspot versus 67.9 (± 0.49) and 67.9 Gy (± 0.52) in 18F-miso and per-treatment 18FDG, respectively. In scenario 3, the mean D95% was 72.2 (± 0.27) Gy to 18F-miso versus 70.4 (± 0.74) and 69.5Gy (± 0.74) for 18FDG hotspot and per-treatment 18FDG, respectively. In scenario 4, the mean D95% was 73.1 (± 0.3) Gy to 18FDG per-treatment versus 71.9 (± 0.61) and 69.8 (± 0.61) Gy for 18FDG hotspot and 18F-miso, respectively. The dose/volume constraints to OARs were matched in all scenarios.ConclusionEscalated doses can be selectively planned in NSCLC target volumes delineated on 18FDG and 18F-miso PET/CT functional images. The most relevant strategy should be investigated in clinical trials.Trial registration(RTEP5, NCT01576796, registered 15 june 2012)

Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia

“…Hypoxia-induced chemoresistance may be mediated by several factors, including the induction of various genes controlling cell metabolism and survival [ 3 ] as well as induction of stemness [ 60 ]. Therefore, information about tumor hypoxia may help to individualize therapy concepts, e.g., by dose escalation of radiation therapy in hypoxic tumors [ 51 ] as recently reported for non-small cell lung cancer [ 61 ]. Longitudinally monitoring tumor hypoxia during the course of treatment could be beneficial as tumor hypoxia may decrease during radiochemotherapy [ 51 , 62 ] which could make a readjustment of treatment necessary.…”

Advanced Imaging Techniques for Radiotherapy Planning of Gliomas

“…It has been shown that Hypoxia PET imaging may aid RT planning in patients with lung and head and neck cancer by safely guiding dose escalation to tumor regions with higher tracer uptake [ 154 , 155 , 156 ]. Uptake of hypoxia-targeting radiopharmaceuticals in brain tumors was found to correlate with the expression of endogenous markers of hypoxia, such as HIF-1α [ 157 , 158 ], and demonstrated a negative impact on survival outcomes [ 159 , 160 , 161 ].…”

Use of Baseline 18F-FDG PET/CT to Identify Initial Sub-Volumes Associated With Local Failure After Concomitant Chemoradiotherapy in Locally Advanced Cervical Cancer

“…Authors therefore suggested to use a 70% (for lung tumor) and 60% (for esophageal tumor) SUV max threshold to identify subvolume of high 18 F-FDG uptake on pretreatment PET/CT scans as the target areas for potential radiotherapy dose boosting. With this hypothesis, Thureau et al (34) has recently assessed the feasibility of a FDG PET-guided dose escalation with IMRT in 21 non squamous cell lung carcinomas (RTEP5 trial, NCT01576796). In using a boost to FDG hotspot delineated with 70% SUV max threshold on primary tumor, the mean dose to planning target volume was 72.5 ± 0.25 Gy and the dose/volume (D/V) constraints to organ at risk (OAR) were respected.…”