Adaptive brachytherapy treatment planning for cervical cancer using FDG-PET

Int. J. Radiation Oncology Biol. Phys., Vol. 67, No. 1, pp. 91–96, 2007 Copyright © 2007 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/07/$–see front matter doi:10.1016/j.ijrobp.2006.08.017 CLINICAL INVESTIGATION Cervix ADAPTIVE BRACHYTHERAPY TREATMENT PLANNING FOR CERVICAL CANCER USING FDG-PET LILIE L. LIN, M.D.,* SASA MUTIC, B.S.,* DANIEL A. LOW, PH.D.,* RICHARD LAFOREST, PH.D.,† MILOS VICIC, PH.D.,* IMRAN ZOBERI, M.D.,*§ TOM R. MILLER, M.D., PH.D.,‡§ ‡§ AND PERRY W. GRIGSBY, M.D.* *Radiation Oncology Department, †Division of Radiological Sciences, ‡Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, and §Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO Purpose: A dosimetric study was conducted to compare intracavitary brachytherapy using both a conventional and a custom loading intended to cover a positron emission tomography (PET)-defined tumor volume in patients with cervix cancer. Methods and Materials: Eleven patients who underwent an [18F]-fluoro-deoxy-D-glucose (FDG)-PET in conjunction with their first, middle, or last brachytherapy treatment were included in this prospective study. A standard plan that delivers 6.5 Gy to point A under ideal conditions was compared with an optimized plan designed to conform the 6.5-Gy isodose surface to the PET defined volume. Results: A total of 31 intracavitary brachytherapy treatments in conjunction with an FDG-PET were performed. The percent coverage of the target isodose surface for the first implant with and without optimization was 73% and 68% ( p ⴝ 0.21). The percent coverage of the target isodose surface for the mid/final implant was 83% and 70% (p ⴝ 0.02), respectively. The dose to point A was higher with the optimized plans for both the first implant (p ⴝ 0.02) and the mid/last implants (p ⴝ 0.008). The dose to 2 cm3 and 5 cm3 of both the bladder and rectum were not significantly different. Conclusions: FDG-PET based treatment planning allowed for improved dose coverage of the tumor without significantly increasing the dose to the bladder and rectum. © 2007 Elsevier Inc. PET, treatment planning, cervix, brachytherapy. Treatment for patients with locally advanced cervix cancer includes a combination of external beam radiotherapy and intracavitary brachytherapy with concurrent cisplatin-based chemotherapy (1–3). The brachytherapy component of therapy follows a method developed decades ago. This system of dose prescription is based on the Manchester system that was designed to deliver specific doses to defined points irrespective of the three-dimensional (3D) extent of a patient’s tumor. In patients with locally advanced disease, the ability to deliver high doses to the tumor is limited by the surrounding normal tissues. Higher doses to point A have been correlated with improved local control, but come at the expense of higher normal tissue toxicity. Additionally, though there is a high pelvic control rate with the current method of treatment for patients with early stage cervical cancer, the reported incidence of late Grade 3 or 4 complications with concurrent chemoradiotherapy is 11% (2). In a retrospective study by Perez (4), the incidence of Grade 2 or 3 rectal or urinary complications with doses below 75– 80 Gy was 5%. However, with higher doses, the incidence increased to greater than 10% (4). One of the advantages of imageguided brachytherapy treatment planning for both groups of patients is the ability to conform the target isodose surface to the gross and microscopic tumor volume by adjusting the dwell times and positions, which may potentially allow for decreased doses to the surrounding normal tissues as well. The ability to perform 3D treatment planning for cervix cancer is predicated on our ability to accurately define the tumor volume which we have previously demonstrated with [18F]-2-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) (5). Our group has published several studies on the use of FDG-PET imaging for brachytherapy treatment planning (6 – 8). Several groups have published on the experience of magnetic resonance imaging (MRI) for conformal brachytherapy treatment planning (9, 10). With MRI or computed tomography (CT) imaging, however, special applicators are required. Additionally, a recent multi-institution Reprint requests to: Perry W. Grigsby, M.D., Department of Radiation Oncology, Box 8224, Washington University School of Medicine, 4921 Parkview Place, Lower Level, St. Louis, MO 63110. Tel: (314) 362-8502; Fax: (314) 747-9557; E-mail: [email protected] Supported in part by NIH R01 grants CA85797 and CA84409. Conflict of interest: none. Received Jan 31, 2006, and in revised form Aug 1, 2006. Accepted for publication Aug 4, 2006. INTRODUCTION 91 92 I. J. Radiation Oncology ● Biology ● Physics study of CT and MRI imaging in cervix cancer found that both imaging modalities had poor sensitivity for the detection of advanced stage disease. FDG-PET imaging provides physiologic information that is not provided by CT or MRI imaging. To evaluate 3D treatment planning for brachytherapy with FDG-PET imaging, we compared the dose distribution from a standard plan with a plan allowing for more conformal coverage of the target isodose surface to the PET defined volume. METHODS AND MATERIALS Patient characteristics Eleven patients with biopsy proven invasive cervical cancer treated at Washington University in St. Louis were included in this analysis. These patients were enrolled on a prospective study approved by the Washington University Human Studies Committee to examine the feasibility and additional benefit of obtaining multiple sequential FDG-PET imaging studies during the course of definitive radiotherapy. This dosimetric study represents a secondary retrospective analysis of the initial study. The limited number of FDG-PET imaging studies obtained during the course of therapy was supported by National Institutes of Health R01 grants CA85797 and CA84409. Written informed consent was obtained from all patients. Patients were entered onto this study between December 2002 and January 2004. The patients were staged clinically by the International Federation of Gynecologic Oncology (FIGO) criteria (11). There were 3 patients with Stage Ib, 5 with Stage IIb, and 3 with Stage IIIb cervical cancer. All patients had histologic confirmation of invasive carcinoma of the uterine cervix. Patient age ranged from 39 to 76 years (median 55 years). Radiation therapy All patients were treated with a combination of external irradiation and intracavitary brachytherapy with curative intent. Therapy for cervical cancer was based on the standard treatment policies at Washington University in St. Louis (12). A dose of 10.8 –19.8 Gy (median, 19.8 Gy) was given to the whole pelvis, with an additional 30.6 –39.6 Gy (median, 30.6 Gy) to the pelvis with a customized step wedge. The prescription delivered a cumulative dose to point A between 69.7 and 88.4 Gy (median, 84.1 Gy) in low-dose-rate equivalent (or a median dose of 59 Gy in high dose rate [HDR], 650 cGy to point A ⫻ 6) depending on the patient’s stage of disease. The patient that received 69.7 Gy to point A had initial FIGO Stage Ib1 disease. A conversion factor of 0.6 was used at our institution to convert between low dose rate and HDR dose for the brachytherapy portion of the treatment. The majority of patients received weekly cisplatin chemotherapy. All patients received intracavitary brachytherapy at either low dose rate (2 patients) or HDR (9 patients). Brachytherapy was performed during the course of irradiation using standard Fletcher-Suit tandem and ovoid applicators. Brachytherapy treatment was administered using two-dimensional orthogonal treatment planning as is standard at our institution. PET imaging All patients underwent initial FDG-PET or PET/CT for lymph node staging purposes. Initial FDG-PET scans were transferred to the Xio treatment planning system (Computerized Medical Systems, St. Louis, MO) and the initial cervical tumor volume was contoured and recorded. For tumor delineation, the threshold im- Volume 67, Number 1, 2007 age intensity was set at 40% of the peak tumor intensity (5). The tumor was then contoured at the edge of the enhancing area. Each patient underwent FDG-PET imaging in conjunction with their first, middle (either third or fourth), and final brachytherapy treatment if receiving HDR brachytherapy or with both brachytherapy treatments if receiving low dose rate brachytherapy. Placement of the tandem and ovoid applicators was performed per routine at our institution after urinary catheterization using a Foley catheter that was left in place for continuous urinary drainage. Because of the potential of artifacts related to intense FDG activity in the urinary tract, we used a combination of intravenous hydration and diuretic agents to minimize the FDG accumulation in these structures. For patients receiving HDR brachytherapy, patients completed their HDR treatment before FDG-PET imaging with tandem and ovoid applicators in place. For patients receiving low-dose-rate brachytherapy, the FDG-PET imaging was obtained after placement of the applicators, but before source loading. The protocol for FDG-PET imaging has been previously published (6). FDG-PET 3D treatment planning The FDG-PET images after scanning were transferred to the XiO brachytherapy 3D treatment planning system. The applicators containing FDG were localized on the images and contoured for applicator reconstruction. Normal structures including the bladder and rectum from the anus to the rectosigmoid junction were contoured. The gross tumor volume (GTV) was defined as any area with abnormal enhancement as visualized on FDG-PET imaging. The edge of the enhancing area was contoured as previously described (5, 6). No margin for microscopic disease was added to the GTV. Catheter positions were reconstructed as previously described (8). The source positions were referenced to the tips of the applicators at the cranial image at which the FDG tubes within the applicator were visible. Multiplanar reconstruction (sagittal and coronal) were used to verify the proper identification, as previously described (7). The standard source distribution based on our clinical protocols for HDR brachytherapy treatment is designed to deliver 6.5 Gy to point A. A 3D brachytherapy treatment plan for each patient was constructed using the standard source loading at the time of initial treatment. For the purposes of this study and for ease of comparison, all FDG-PET based treatment plans were performed for HDR delivery. The 3D dose distributions were calculated to determine the 3D tumor volume covered by the 6.5-Gy isodose surface and the minimal isodose surfacing covering 100% of the 3D tumor volume. The International Commission on Radiation Units and Measurements Report 38 (ICRU-38) (13) bladder point was identified as the center of the Foley bulb in the 3D FDG-PET image reconstruction. The ICRU-38 rectal point was placed 0.5 cm behind the posterior vaginal wall at the level of the line intersecting the centers of the active dwell positions in the ovoids. Point A was identified according to the classic definition relative to the reconstructed applicators. Dose–volume histograms were calculated for the tumor, bladder, and rectum. The dose to 2 cm3 of bladder and rectum were also calculated. For each implant, we performed a separate, optimized HDR plan. The treatment planning goal for each optimized implant plan was to cover at least 80% of the GTV with the target 6.5-Gy isodose surface while limiting the dose to 2 cm3 of bladder to less than 7.5 Gy and 2 cm3 of rectum to less than 5 Gy. For a standard loading pattern, 15 dwell positions were typically used: 9 within the tandem and 3 within each ovoid to deliver 6.5 Gy to point A for each HDR implant. To achieve the optimal dose coverage of the PET-defined Brachytherapy treatment planning for cervix using FDG-PET ● L. L. LIN et al. 93 Fig. 1. First implant for Patient #4 without (a) and with (b) optimization to the positron emission tomography (PET)-defined tumor volume. Bladder, yellow; PET tumor volume, red; rectum, brown. Target isodose surface (6.5 Gy) is purple. tumor volume for each implant, dwell positions and times were altered both within the tandem and ovoids. The tandem dwell positions were frequently shifted to account for both the location of the tumor as well as the bladder and rectum. For each plan, the doses to the ICRU bladder and rectal reference points, as well as point A, were also recorded. RESULTS Eleven patients underwent a total of 31 intracavitary brachytherapy treatments in conjunction with FDG-PET imaging. PET-assisted treatment planning data from the first implant for 11 patients, mid-implant for 9 patients, and the final implant for 6 patients compose this analysis. Three patients had no tumor FDG uptake on the mid or last implant and those insertions were not included in this study, though data from their first or mid-implant was included in the analysis. Among the 3 patients without evidence of uptake on their mid or final implant brachytherapy implant, 2 patients had initial FIGO Stage IIb disease and 1 patient had initial FIGO Stage Ib1 disease. For the purposes of this analysis, because of the small patient numbers, the data from the mid and last implant were combined. The mean tumor size for the first implant was 56 cm3 (range, 7–137 cm3); the mean tumor size for the mid and last implant was 17 cm3 (range, 2–38 cm3). The percent coverage of the target isodose surface for the first implant with and without optimization was 73% and 68% (p ⫽ 0.21). The percent coverage of the target isodose surface for the mid and last implant with and without optimization was 83% and 70% (p ⫽ 0.02). Figure 1 and Fig. 2 show the standard vs. conformal plans for the first and final implant of 1 patient. It demonstrates the improvement in coverage with the conformal plan, which was significant with the final implant. The mean dose to 95% of the GTV for the first implant for the standard and Fig. 2. Final implant for Patient #4 without (a) and with (b) optimization. 94 I. J. Radiation Oncology ● Biology ● Physics conformal plans was 4.2 Gy and 4.25 Gy, respectively. The mean dose to 95% of the GTV for the mid and final implants for the standard and conformal plans was 5.4 Gy and 4.6 Gy, respectively. The dose to point A was higher with the optimized plans for both the first implant (p ⫽ 0.02) and the mid and last implants (p ⫽ 0.008). The mean dose to 2 cm3 of bladder was 6.8 Gy and 6.2 with the standard and conformal plans, respectively (p ⫽ 0.70). The mean dose at the ICRU bladder reference point dose was not significantly different for the standard and conformal plans, 4.7 Gy and 5.1 Gy, respectively (p ⫽ 0.75). The mean dose to 2 cm3 of rectum was 3.6 Gy and 3.7 Gy with the standard and conformal plans, respectively (p ⫽ 0.87). The mean dose at the ICRU rectal reference point was 3.6 vs. 2.7 Gy for the standard vs. conformal plan, respectively (p ⫽ 0.0239). Additionally, the dose to 5 cm3 of bladder and rectum were not significantly different in the plans with and without optimization. We also analyzed the significance of the dose to the ICRU bladder and rectal reference points compared to dose to 2 cm3 of normal tissue for a standard plan. The dose to 2 cm3 of bladder was significantly higher than the dose to the ICRU bladder reference point, p ⬍ 0.0001, whereas the dose to 2 cm3 of rectum was not significantly different from the dose to the ICRU rectal reference point for a standard plan, p ⫽ 0.63. DISCUSSION [18F]-fluoro-deoxy-D-glucose-PET is an imaging modality that is now routinely used for external beam treatment planning for a variety of malignancies including cervix, lung, and head-and-neck cancers. At our institution, we use FDG-PET imaging to define the extent of external beam radiotherapy portals. Patients who have FDG-PET positive para-aortic nodal disease have their external beam radiotherapy portals increased to include the para-aortic region. Patients that have no nodal disease or pelvic nodal disease on FDG-PET imaging are treated with a standard pelvic portal. The brachytherapy component of treatment, however, continues to be planned using radiographs with point A and dose to the ICRU rectal and bladder reference points reported for each implant. This method of treatment planning is designed to administer specific doses to defined points independent of the 3D extent of a patient’s disease. Several groups have investigated the use of other imaging modalities including CT and MRI for 3D treatment planning (9, 14 –16). The goal of 3D treatment planning for cervix cancer is to deliver a more conformal dose to the target volume while minimizing the dose to the organs at risk, specifically the bladder and rectum. Our group has published several studies on the use of FDG-PET for brachytherapy treatment planning (6 – 8). Our initial pilot feasibility study of FDG-PET imaging for brachytherapy treatment planning included 11 patients with cervix cancer who underwent an FDG-PET with their initial Volume 67, Number 1, 2007 brachytherapy treatment (8). We were able to demonstrate in that study that FDG-PET treatment planning is feasible and provides important information as to the 3D extent of the disease. A follow-up study was performed that included an additional group of patients who underwent sequential FDG-PET imaging during the course of their radiation treatment. In that analysis, FDG-PET imaging identified the tumor response in the individuals that underwent sequential imaging (6, 17). This group of patients composed this dosimetric study to determine whether FDGPET imaging throughout the course of therapy in conjunction with intracavitary brachytherapy could allow for optimization of the dose distribution to the tumor volume, while accounting for the dose constraints to the bladder and rectum. Wachter-Gerstner et al. have conducted a study analyzing the doses to the bladder and rectum using both organ contours and organ wall contours (18). In their study, they found that for volumes less than 5 cm3, organ wall contours provided a good estimate of the dose to the organ walls. The mean volumes for the bladder and rectum in their study were 197 cm3 and 58 cm3, respectively. In our study, the mean volume of the bladder and rectum were 163 cm3 and 58 cm3, respectively. It is impossible to contour organ walls using only FDG-PET imaging, but our volumes are in line with their analysis. For the purposes of this dosimetric study, we chose to use the dose to 2 cm3 of the bladder and rectum as the normal tissue constraint. This was both to facilitate comparisons with other groups that have investigated image-guided brachytherapy and because 2 cm3 of dose to normal tissue has been assumed to be of potential clinical significance (19). In this analysis, the dose at the ICRU bladder reference point underestimated the dose to 2 cm3 of bladder, which has also been observed by other groups (18, 20). Wachter-Gerstner et al. has reported that this may be due to Foley balloon positioning, especially with larger bladder volumes (18). In contrast, there was a good concordance between the dose at the ICRU rectal reference point and the dose to 2 cm3 of rectum (p ⫽ 0.13). This observation was also described by other groups that have reported their results with CT- or MRI-based brachytherapy treatment planning (18, 20). Other groups have performed dosimetric studies using CT or MRI for brachytherapy treatment planning. In a study by Brooks et al. (10), 15 patients with nonmetastatic cervix cancer receiving definitive radiation therapy with or without concurrent chemotherapy were part of a dosimetric study evaluating the use of CT for brachytherapy treatment planning. A standard plan designed to deliver 6 Gy to point A was compared with a second plan to deliver 6 Gy to the PTV. The Baltas conformal index was used for dosimetric comparison and found that the mean Baltas conformal index values were 0.39 for the conformal plan and 0.33 for the standard plan (p ⫽ 0.001). The mean rectal D2mL was not significantly different for the conformal plan compared with the standard plan, 4.02 Gy vs. 3.74 Gy (p ⫽ 0.23). Similarly, the mean bladder D2mL was not significantly different Brachytherapy treatment planning for cervix using FDG-PET for the conformal plan vs. the standard plan, 6.05 Gy vs. 5.48 Gy (p ⫽ 0.06). Wachter-Gerstner et al. (18) have evaluated the effect of using CT and MRI compared with radiography for adapting the dose distribution to the target volume while minimizing the dose to the organs at risk. Fifteen patients had MRI examination at the time of brachytherapy with applicators in place; 10 of those patients also had a CT scan performed at the same time. The treatment planning goal was to encompass the maximum amount of target volume within the prescription dose without exceeding dose constraints to the bladder and rectum. MRI-based treatment planning allowed for dose escalation by a mean factor of 1.26 compared with radiography-based treatment planning with borderline significance (p ⫽ 0.08). The minimum dose to 2 cm3 of bladder and rectum with the MRI or CT plan were not increased compared with the radiographybased plan. In our study, we were able to demonstrate that FDGPET– based treatment planning allowed for improved coverage to the PET defined tumor volume, which was most pronounced for the mid and final brachytherapy implants. Our treatment planning constraints was to cover at least 80% of the GTV with the 6.5-Gy isodose line. In making a transition from point based to 3D treatment planning, there is no point of reference for determining the optimal coverage to the GTV. In our study, the median coverage of the GTV for all implants with the 6.5-Gy isodose surface using conventional loading was 73.5%. We sought to improve on the conventional plan by using 80% coverage of the GTV as our goal. The likely explanation as to why the optimized plan did not result in significantly improved tumor coverage for the initial implants is that tumor volumes were larger. In a previous report by our group that included 32 patients with cervical cancer who underwent at least one FDG-PET imaging study during the course of chemoradiotherapy, the mean volume of the PET defined tumor volume decreased during the course of treatment (17). In a study of MRI-based brachytherapy treatment planning, Kirisits et al. also found that the overall treatment volume decreased from the initial to the final brachytherapy insertion (9). In our study, because of the larger tumor volumes at the initial brachytherapy implant, the rectum was the dose limiting organ in 3 of the 5 patients in which the optimized plan resulted in an improvement, though the target coverage of 80% of the GTV could not be satisfied. For the remaining 2 patients, high doses to the bladder resulted in unsatisfactory plans. During the planning process, the rectal dose limits were prioritized over the bladder dose limits. It is possible that improvement in rectal packing could have resulted in higher doses to the GTV. Optimized plans did not result in significantly higher doses to 2 cm3 or 5 cm3 of bladder or rectum. The inability to detect a difference in normal tissue dose distribution may be secondary to the heterogeneity in tumor size in our population of patients, as well as the small ● L. L. LIN et al. 95 number of patients. Additionally, examining the dose to 2 cm3 and 5 cm3 of rectum and bladder, which have been used in other imaging based intracavitary studies, may have limitations in our system. There are limited data correlating dose to the normal structures and tissue toxicity. Our treatment planning goal for the optimized plans was to limit the dose to 2 cm3 of bladder and rectum to less than 7.5 and 5 Gy, respectively. One of the limitations of our current knowledge of 3D treatment planning for cervix cancer is that data correlating dose to normal structures and toxicity are limited. As other groups begin to report their experience with 3D treatment planning for brachytherapy, our dose constraints for normal structures using 3D treatment planning will likely evolve. We chose to exclude the mid or final implants of 3 patients who had no evidence of FDG-PET uptake on imaging because this was a dosimetric study designed to determine whether a conformal plan would result in improved coverage of the PET defined gross tumor compared with a standard plan with conventional loading. During the course of this study, we observed that there is a subset of patients who have rapidly responding tumors, as we have previously described, who have no evidence of abnormal FDG uptake on imaging during the course of therapy (17). These patients may not need the standard 75–90 Gy to point A dose that has been recommended by the American Brachytherapy Society for patients with FIGO Stage Ib2 to IIIb disease (21). For these patients, including patients with no FDG uptake on imaging during the course of therapy, we may recommend defining a microscopic target volume in addition to the PET defined GTV, which was not initially defined for this study, but would be aided by FDGPET/CT imaging. We have previously demonstrated that the presence of abnormal FDG uptake on posttreatment imaging was predictive of death and may be an optimal surrogate measure for tumor control during the course of therapy (22). Further studies will be needed to confirm this conclusion. We are not using FDG-PET for brachytherapy treatment planning, but are developing a protocol to use FDGPET/CT for adaptive treatment planning for cervix cancer. The initial funding of this study by the National Institutes of Health limited the total number of patients that could be evaluated in this study. As such, one of the major limitations of this study is the limited patient numbers. Further studies with a larger number of patients are planned with the use of FDG-PET/CT planning. One of the limitations of our current treatment planning system is the inability to summate the doses from the brachytherapy implants and the external beam radiotherapy in a 3D treatment plan. As treatment planning systems continue to evolve, it may now be possible to report the cumulative 3D dose to normal structures. Longer follow-up will be necessary to determine the optimum dose constraints to normal tissues. 96 I. J. Radiation Oncology ● Biology ● Physics Volume 67, Number 1, 2007 REFERENCES 1. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatinbased radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999;340:1144 –1153. 2. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 1999;340: 1137–1143. 3. Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 1999;340:1154 –1161. 4. Perez CA, Breaux S, Bedwinek JM, et al. Radiation therapy alone in treatment of the uterine cervix. II. Analysis of complications. Cancer 1984;54:235–246. 5. Miller TR, Grigsby PW. Measurement of tumor volume by PET to evaluate prognosis in patients with advanced cervical cancer treated by radiation therapy. Int J Radiat Oncol Biol Phys 2002;53:353–359. 6. Lin LL, Mutic S, Malyapa RS, et al. Sequential FDG-PET brachytherapy treatment planning in carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2005;63:1494 –1501. 7. Mutic S, Grigsby PW, Low DA, et al. PET-guided threedimensional treatment planning of intracavitary gynecologic implants. Int J Radiat Oncol Biol Phys 2002;52:1104 –1110. 8. Malyapa RS, Mutic S, Low DA, et al. Physiologic FDG-PET three dimensional brachytherapy treatment planning for cervical cancer. Int J Radiat Oncol Biol Phys 2002;54:1140 – 1146. 9. Kirisits C, Potter R, Lang S, et al. Dose and volume parameters for MRI-based treatment planning in intracavitary brachytherapy for cervical cancer. Int J Radiat Oncol Biol Phys 2005;62:901– 911. 10. Brooks S, Bownes P, Lowe G, et al. Cervical brachytherapy utilizing ring applicator: Comparison of standard and conformal loading. Int J Radiat Oncol Biol Phys 2005;63:934 –939. 11. Benedet JL, Bender H, Jones H, 3rd, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 2000;70:207–312. 12. Perez C. Uterine cervix. In: Perez C, Brady L, editors. Principles and practice of radiation oncology. 2nd ed. Philadelphia: J. B. Lippincott; 1992. pp. 1143–1202. 13. ICRU Report 38. Dose and volume specification for reporting intracavitary therapy in gynecology. Bethesda, MD: International Commission on Radiation Units and Measurements; 1985. 14. Ling CC, Schell MC, Working KR, et al. CT-assisted assessment of bladder and rectum dose in gynecological implants. Int J Radiat Oncol Biol Phys 1987;13:1577–1582. 15. Schoeppel SL, Ellis JH, LaVigne ML, et al. Magnetic resonance imaging during intracavitary gynecologic brachytherapy. Int J Radiat Oncol Biol Phys 1992;23:169 –174. 16. Kim R, Pareek P. Radiography-based treatment planning compared with computed tomography (CT)-based treatment planning for intracavitary brachytherapy in cancer of the cervix: Analysis of dose-volume histograms. Brachytherapy 2003;2: 200 –206. 17. Lin LL, Yang Z, Mutic S, et al. FDG-PET imaging for the assessment of physiologic volume response during radiotherapy in cervix cancer. Int J Radiat Oncol Biol Phys 2006;65: 177–181. 18. Wachter-Gerstner N, Wachter S, Reinstadler E, et al. Bladder and rectum dose defined from MRI based treatment planning for cervix cancer brachytherapy: Comparison of dose-volume histograms for organ contours and organ wall, comparison with ICRU rectum and bladder reference point. Radiother Oncol 2003;68:269 –276. 19. van den Bergh F, Meertens H, Moonen L, et al. The use of a transverse CT image for the estimation of the dose given to the rectum in intracavitary brachytherapy for carcinoma of the cervix. Radiother Oncol 1998;47:85–90. 20. Pelloski CE, Palmer M, Chronowski GM, et al. Comparison between CT-based volumetric calculations and ICRU reference-point estimates of radiation doses delivered to bladder and rectum during intracavitary radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys 2005;62:131–137. 21. Nag S, Chao C, Erickson B, et al. The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2002;52:33– 48. 22. Grigsby PW, Siegel BA, Dehdashti F, et al. Posttherapy [18F] fluorodeoxyglucose positron emission tomography in carcinoma of the cervix: Response and outcome. J Clin Oncol 2004;22:2167–2171.