A clearly visualized halo was successfully implemented in GTV contouring in cervical cancer, resulting in decreased inter-observer variability in radiation therapy planning. Additionally, PET/CT has the ability to quantify treatment response using anatomic biologic value. PET/CT remains an important clinical tool in staging for newly diagnosed cervical cancer [9
]. Still its utility and role in treatment planning has yet to be fully elucidated, as it is currently being incorporated into investigational studies [11
]. Consensus among members of the Society of Gynecologic Oncologists show that the use of PET/CT in patients with cervical cancer remains highly underutilized [12
]. Our study aimed to reveal strengths of PET/CT compared to standard CT-based treatment planning by identifying a more specific GTV.
Our results suggest a large difference in independent radiation oncologists’ GTV’s when based on CT-based planning. Planning with PET/CT to create the GTV-ABC resulted in increase concordance by the two radiation oncologists. Difficulty with PET/CT-based planning is rooted in inter-institutional variability in defining the threshold for delineating malignant disease according to physiologic images. A variety of tumor criteria for identifying GTV have been previously described. A series of publications have arbitrarily advocated the FDG-avid volume as the region encompassed by the 50% intensity level relative to the tumor maximum intensity [13
]. Others have used auto-contours of SUV levels of 2.5 to delineate tumor [15
]. Another issue complicating PET/CT is that the threshold of PET images can and often needs to be adjusted on a case-by-case basis and can introduce variability among independent observers [16
In addition to this study, we have previously described [7
] the use of an anatomic biologic volume to represent the contoured GTV which was derived from a “halo” found on PET/CT. As we saw in all three studies, this halo was used to contour the PET/CT-based GTV with a decrease in interobserver GTV variability. This halo was irrespective of threshold level and has been reproduced in a variety of sites and viewing parameters (). In PET/CT, electron-positron interaction result in two 511 keV gamma photons being emitted at 180 degrees to each other; hence, it is possible to localize their source along a straight line of coincidence. We believe the halo is due to a differential photon attenuation cause by the difference in tissue density at the interface of the tumor cells and surround normal tissue. This differential attenuation results in significant uptake in the tumor itself, then a rim characterized by a lack of signal registration, followed by a halo of signal registration, incorrectly localized from the tumor perimeter. We do not believe the halo is of biological significance. It is simply a physical property of photon attenuation and localization inherent in PET/CT registration.
Figure 3 The “Anatomic Biologic Halo” visualized in a variety of sites: lung (A), nasopharynx (B), and pancreas (C). Also seen at the bottom of the figure (D) is the reproducibility of the halo in all PET visualization filters. The 1st box on the (more ...)
Current practice guidelines among radiation oncologists for external beam radiotherapy delineate the superior border of the pelvic field at L4/L5 [5
]. Inferiorly the border is at least 3-4 cm below the lowest extent of cervical or vaginal disease. Lateral borders are placed 1.5-2 cm lateral to the bony margins of the true pelvis. These borders have historically been used to ensure coverage of potential soft tissue tumor extent, lymph node drainage, and pathways of regional spread. These landmarks were rooted in skeletal anatomy seen on radiographs before the advent of CT and PET technology. It is already observed in contouring GTV for IMRT plans, that cervix and adjacent 2-3 cm of uterine tissues are used [17
]. PET/CT has been shown to be highly sensitive and specific for locoregional and metastatic spread of cervical cancer with a negative predictive value of 96% [3
]. The SUV level of the tumor at diagnosis by PET has been correlated as a sensitive biomarker of treatment response and prognosis [18
]. With sophisticated modalities in evaluating anatomy and extent of disease in addition to the utility of IMRT, the necessity in covering the entire pelvis in early-stage cervical cancer comes in to question. An example of the reduction in volume of contours drawn on PET/CT in comparison to CT alone is shown in the sagittal plan in . In a study of 611 patients with cervical cancer who underwent radical hysterectomy with bilateral salpingo-oophorectomy, uterus involvement was found in 12.1% of the specimens [19
]. Evaluation of operative specimens of 230 patients with squamous cell carcinoma who underwent radical hysterectomy with pelvic lymphadenectomy revealed that extension beyond the cervix to the anterior parametria was in 23% of the cases and into the uterosacral ligaments in about 15% of the cases. Paracervical extension observed in 26% of the cases was related to the maximum depth of stromal invasion [20
Figure 4 Sagittal view of reduction of contour volume when PET-CT based planning used for cervical cancer (B) in comparison to volumes drawn with CT alone (A). Observer 1 and 2’s contours are indicated by the red and blue contours on each of the scans, (more ...)
IMRT has had a definitive role in a variety of pelvic malignancies, but until recently its use in cervical cancer has not been completely defined, likely secondary to difficulty delineating tumor volume and organ motion. However, whenever IMRT is utilized, PET/CT seems an essential adjunct to aid planning. Kidd and associates evaluated the role of IMRT in treating a group of locally advanced cervical cancer, all IMRT patients had PET/CT simulation prior to treatment. The IMRT group showed significantly improved overall and cause-specific survival [17
]. IMRT use in cervical cancer has been demonstrated to produce equivalent or better results in treatment of cervical cancer with single institution experience [12
]. Using, PET/CT simulation for tumor delineation and the natural history of disease progression, IMRT is the logical progression to obtain similar tumor control with less toxicity. FDG-PET will be a crucial component in delineating clinically relevant and reproducible tumor volumes in cervical CA given the difficulty of tumor volume visualization on CT alone.