18F-FLT PET/CT for early response monitoring and dose escalation in oropharyngeal tumors.
Accelerated tumor cell proliferation is an important mechanism adversely affecting therapeutic outcome in head and neck cancer. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a PET tracer to noninvasively image tumor cell proliferation. The aims of this study were to monitor early tumor response based on repetitive (18)F-FLT PET/CT scans and to identify subvolumes with high proliferative activity eligible for dose escalation.


METHODS
Ten patients with oropharyngeal tumors underwent an (18)F-FLT PET/CT scan before and twice during radiotherapy. The primary tumor and metastatic lymph nodes (gross tumor volume, or GTV) were delineated on CT (GTV(CT)) and after segmentation of the PET signal using the 50% isocontour of the maximum signal intensity or an adaptive threshold based on the signal-to-background ratio (GTV(SBR)). GTVs were calculated, and similarity between GTV(CT) and GTV(SBR) was assessed. Within GTV(SBR), the maximum and mean standardized uptake value (SUV(max) and SUV(mean), respectively) was calculated. Within GTV(CT), tumor subvolumes with high proliferative activity based on the 80% isocontour (GTV(80%)) were identified for radiotherapy planning with dose escalation.


RESULTS
The GTV(CT) decreased significantly in the fourth week but not in the initial phase of treatment. SUV(max) and SUV(mean) decreased significantly as early as 1 wk after therapy initiation and even further before the fourth week of treatment. For the primary tumor, the average (+/-SD) SUV(mean) of the GTV(SBR) was 4.7 +/- 1.6, 2.0 +/- 0.9, and 1.3 +/- 0.2 for the consecutive scans (P < 0.0001). The similarity between GTV(CT) and GTV(SBR) decreased during treatment, indicating an enlargement of GTV(SBR) outside GTV(CT) caused by the increasing difficulty of segmenting tracer uptake in the tumor from the background and by proliferative activity in the nearby tonsillar tissue. GTV(80%) was successfully identified in all primary tumors and metastatic lymph nodes, and dose escalation based on the GTV(80%) was demonstrated to be technically feasible.


CONCLUSIONS
(18)F-FLT is a promising PET tracer for imaging tumor cell proliferation in head and neck carcinomas. Signal changes in (18)F-FLT PET precede volumetric tumor response and are therefore suitable for early response assessment. Definition of tumor subvolumes with high proliferative activity and dose escalation to these regions are technically feasible.
Troost
Esther G C
EG
Department of Radiation Oncology, Institute of Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. e.troost@rther.umcn.nl
Bussink
Johan
J
Hoffmann
Aswin L
AL
Boerman
Otto C
OC
Oyen
Wim J G
WJ
Kaanders
Johannes H A M
JH
D000368:Aged; D049109:Cell Proliferation; D015224:Dideoxynucleosides; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000532:radiotherapy*; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden
D015224:Dideoxynucleosides; C002854:alovudine