Nonsignificant rectal D2cc differences among planned and delivered brachytherapy fractions (14.25 vs 13.95 Gy, p = 0.155) were observed in a recent study.79 In that study, a nonsignificant decrease in rectal volumes on the delivered CTs was observed compared to the planning CT. A positive correlation has been demonstrated between rectal volume and Dmax, D0.1cc, D1cc and D2cc, which remained significant in multiple linear regression models.32 Rectal contrast, traditionally, has been used to improve rectal visualization in orthogonal radiographs, although it must be avoided because a CT-based study demonstrated a statistically significant increase of up to 10.4% in some rectal dose parameters.83 This was linked to an increase in the rectal volume of up to 27.6 ± 41.6 cm3. The presence of gas pockets in the rectum during VCB has also been associated with higher rectal doses.84 Removal of these pockets significantly decreased the mean rectum volume by 29% and D2cc by 11% as well as the rectum dose area under the curve by 33%. In light of these data, a prospective trial was carried out to analyze the effect of rectal enemas on rectal dosimetric parameters.85,86 The enema protocol involved two Fleet enemas, the first administered the night before the procedure and the second before hospital admittance for the procedure. No significant dose parameter differences were observed between fractions with or without Fleet enemas.
Patel et al79 observed lower bladder volumes on planning CT compared with the treatment CT acquired before each brachytherapy fraction. At the same time, the delivered bladder D2cc was significantly higher than the planned D2cc (18.83 vs 13.2 Gy, p = 0.0053). Studies comparing full and empty bladders have been reported. A total of 15 patients underwent a CT scan before the first fraction with an empty bladder followed by a second CT scan done with the bladder full.87 This maneuver increased significantly the cylinder-to-bowel distance (1.68 vs 1.2 cm, p = 0.006). The full bladder produced a significant 18.7% bladder D2cc increase and a nonsignificant rectum D2cc increase of 0.5%. A nonsignificant reduction in sigmoid (–15.1%) and bowel (–10.5%) D2cc was observed. Another study reported a reduction of 0.5 Gy on average in bladder doses in 35 out of 45 women with an empty bladder, but 10 out of 45 patients’ bladder doses increased to 0.2 Gy on average.88 D2cc significantly decreased the bladder empty (4.9 vs 4.6 Gy), while V50 increased significantly (10.1% vs 17.7%). It was associated with a significant D2cc bowel dose reduction (4.1 vs 4.6 Gy). Hoskin and Vidler89 carried out a comparative paired analysis with an empty bladder and three full bladder volumes (35, 70 and 100 mL). Mean maximum bladder dose was lower with the empty bladder than with any of the full ones. Stewart et al90 compared CT-planning dose parameters on fractions with an empty bladder and fractions with a full bladder with images acquired 1 hour after consumption of 32 oz of water. D2cc and V50 were significantly greater in the full bladder state (4.56 vs 4.06 Gy and 18.47 vs 10.52 cm3, respectively). The median distance to the nearest point of bowel nearly doubled with the filling of the bladder (11.6 vs 5.75 mm, p = 0.002). The instillation of 180 mL to an empty bladder produced significant D50% bladder and bowel dose reduction of 36.7% and 21.4%, respectively.33 A significant 39.7% D2cc reduction in the bowel values was also seen.
Until recently, two-dimensional (2D) dosimetry calculated from orthogonal RX films was the standard. The spread of CT images raised the need to evaluate the impact of 3D images on dosimetry. Studies have demonstrated the variation of doses to organs depending on the calculation method. Comparisons of International Commission of Radiation Units and Measurements (ICRU) doses on 2D images and maximum and D2cc doses on 3D images were carried out.91 Maximum bladder and rectal doses were 178% and 135% of ICRU doses, respectively. No significant bladder dose differences between D2cc and ICRU doses were observed, but a significant rectal difference was found, with a ratio of D2cc to ICRU equal to 0.87. Bladder and rectal D2cc values were 59% and 64% of maximum doses, respectively. Kim et al92 described significant lower D2cc rectum (82.6% vs 78.2%) and bladder (80.6% vs 77%) doses with 3D planning compared with 2D planning. Hung et al33 reported small but significant lower D2cc doses than the respective ICRU values.
Usually, dose is prescribed to the applicator surface or at 0.5 cm depth. The rationale is the vaginal wall thickness and the depth placement of the lymphatic vessels. In all, 50% of the lymphatic channels are located at 1 mm beneath the mucosa and 7% lie within 3–4 mm.93 A total of 95% of vaginal lymphatic channels are located within the first 3 mm from the vaginal surface. The need to individualize the prescription depth according to the vaginal thickness has been suggested in order to reduce toxicity. Surface dose prescription produces a more uniform dose to the mucosa and at every depth, an acceptable target coverage and almost the same dose falloff compared with 0.5 cm depth dose prescription.94 Dose surface ranged from 81% to 172% for the 0.5-cm depth prescription compared with 90% to 106% for the surface prescription, and large dose variations at the surface appeared with the 2-cm cylinder. A formula was derived to transform 0.5-cm depth dose prescription to surface prescription by magnifying the prescription dose by an M factor that takes into account the cylinder size (S) and activated length (L): M ≈ 1.00 + 0.64 (cm)/L + 1.23 (cm)/S. That study also reported extreme cold and hot spots when no optimization points were used at the cylinder tip.
CUSTOM OR STANDARD RADIOTHERAPY PLANNING
Nowadays, the majority of VCB treatments are 3D planned (83.2%) according to the 2014 ABS survey, but the majority of the respondents (73.4%) only planned the first fraction.63 ABS guidelines do not demand that each fraction of VCB is planned because there is an assumed fixed geometry of the implant. Image at each fraction of three increments costs 35% compared with a single simulation but did not produce any dosimetric advantage.95 Similar results with single-channel or multichannel cylinders were observed; imaging at each fraction was 19% and 22% more expensive, respectively.96 Sabater et al97 compared three approaches for dose summation, a single plan approach that used a crude dose summation of a single plan that was replicated to every fraction and dose summation of customized plans for every fraction using both rigid and deformable registration. No significant rectal dose differences were observed, but some limited differences in bladder dose metrics were found, something which does not justify the higher costs linked to the customized approach. Multichannel cylinders have also been evaluated in this setting,98 and results show an excess of maximum bladder or rectum doses in 41% of cases when a single plan approach was used.
Nowadays, simulation for postoperative EC relies on CT volumetric images, which have proven to detect air pockets around the cylinders74,76,77 or inside the rectum84 or evaluate bladder volume79 and improve dose deposition. Magnetic resonance imaging (MRI) is considered the optimal imaging method to delineate volumes in cervical cancer,99 but its value in EC is less clear and availability is limited, so strategies to integrate clinical images into the radiotherapy workflow have been studied.100 Average absolute percentage dose differences for the bladder, rectum and prescription points on CT and MRI were 2.2%, 2.3% and 2.2%, respectively, and the mean central source deviation was 0.6 mm, which was associated with longer acquisition times in MRI.101 Chapman et al102 carried out sequential MRI and CT scans. They observed using MRI that 69% of the patients had at least 1 cm3 of VC receiving <75% of the prescription dose. The reasons were that areas of undistended vagina now seen in CT and suture material prevented full cylinder insertion. These results question the minimum doses necessary to avoid relapses. Owing to the steep dose gradient, small changes in the structures close to the sources produce large dose–volume histogram changes. Applicator displacement between fractions has a similar effect, so reproducibility is crucial. Although the ABS guidelines recommend a customized plan with each fraction, they state that this may not be necessary, assuming a fixed geometry of the implant for every insertion based on the first fraction.103