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

Abstract

Background: Concomitant 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.

Method: Twenty-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 SUV_max) (plan 2), pre-treatment ¹⁸F-miso target (SUV_max > 1.4) (plan 3) and per-treatment ¹⁸FDG residual (40% of SUV_max). (plan 4).

Results: The 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.

Conclusion: Escalated 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).

Keywords: 18fluoro-deoxy-D-glucose; 18fluoro-misonidasole; Hypoxia; Lung cancer; Positron emission tomography; Radiotherapy.

Fig. 1

Study design. RTCT: radio-chemotherapy; TPS: Treatment Planning System

Fig. 2

Example of dosimetry. Representation of dose (95% to maximum dosi) fr reference plan (66Gy) and three scenario of planification based on PET. PTV are blue, hotspot (BTVm1) is red, FDG pre-RT (BTVm2) is orange and FMISO (BTVh) is dark blue. For each plan the PTV 66 is represented