Brachytherapy

Preplanning

The prostate volume is assessed using three-dimensional (3D) imaging: ultrasound, magnetic resonance imaging (MRI), or computed tomography (CT). An initial plan is run to evaluate pubic arch interference, volume of target and the number, and activity of sources required. With experience, each institution can make an accurate determination of the number and activity of seeds to be ordered based on target volume. The configuration of needles, seeds, and spacers is determined and prepared before the procedure and brought into the operating room ( Fig. 20.1 ).

Real-Time/Dynamic Planning

In this scenario, the plan is developed during the operative procedure. Some preparation is needed to ensure that adequate supplies are available for any eventualities. Advantages include the ability to compensate dynamically for any needle or seed misdirection that may occur during insertion with adjustments to subsequent needle or seed insertion. Second, the practitioner can compensate for edema secondary to needle insertion during the brachytherapy procedure.

Postplanning (Postoperative Dosimetry)

This is used as a treatment quality assessment following the implant. This technique is best practiced by experienced users who will position seeds or catheters a priori with a good idea of the likely dosimetric outcome. Manual or automated seed finding is employed, usually using CT imaging. Postsurgical edema and its resolution may be tracked at intervals; day 0, day 1, and day 30 may be used as proxies for initial, near maximum edema, and steady-state seed configurations, respectively.

Planning Systems

Brachytherapy planning systems are commonly license add-ons to external beam systems and require modules for DICOM import/export, contouring, and 3D display dose volume analytics. The AAPM TG 53 offers a QA strategy to ensure contour quality, positional fidelity, and accurate dose calculation in the system. Commercial isotopes have been evaluated using the TG 43 protocols, and quality systems will have standard seed configurations preloaded and accommodate manual entry of new seed data.

Cervical Cancer

Cervical cancer was one of the first tumors to be treated with brachytherapy, with initial reports of cervical low-dose-rate (LDR) brachytherapy using radium published in 1903. The original principles of treatment with a central tandem and ovoids placed against the cervix have remained. Fortunately, though, we have moved away from the use of wine corks as applicators. For many years, a fixed dosimetry technique based on the Manchester principles was used to deliver a defined dose to point A: 2-cm superior and lateral to the external os. This was then enhanced by the use of the International Commission on Radiation Units (ICRU) rectal and bladder points to predict toxicity to organs at risk (OARs). However, the advent of 3D imaging moved cervical cancer brachytherapy away from point dosing and estimation of dose to OARs to volumetric dosing and precise determination of maximal dose received. This has resulted in fewer toxicities and the ability to deliver higher doses, which results in higher cure rates. It has also moved treatment in general away from LDR and toward high-dose-rate (HDR) or pulsed-dose-rate (PDR) brachytherapy with the ability to optimize dose and conform around the OARs. Randomized studies have shown the equivalence of LDR to HDR with the possibility of lower toxicity with HDR. There are no randomized studies of PDR versus LDR or HDR, but retrospective data indicate that they are likely to be comparable.

The brachytherapy applicator is generally placed operatively. A preoperative MRI close to the time of brachytherapy improves applicator selection and target definition. The patient may receive general anesthesia or regional anesthesia. Analgesia can be maintained throughout the length of a PDR implant or a single-insertion fractionated HDR implant using a spinal catheter. Spinal anesthesia does not cause tumor hypoxia during an HDR implant. Examination under anesthesia confirms the preoperative imaging findings. The cervix is dilated and a uterine tandem is placed, preferably using ultrasound guidance ( Fig. 20.2 ). A variety of applicators are available for intracavitary brachytherapy. For tumors greater than 5 cm, the addition of interstitial needles into specialized applicators is becoming more common because it has brought the ability to deliver interstitial brachytherapy to a wider group ( Fig. 20.3 ). Interstitial template applicators, such as the MUPIT or the Syed-Neblett applicator, should be used to treat disease with marked lateral or vaginal extension, although it is important to maintain a degree of central dose heterogeneity (in contrast to the heterogeneity preferred in interstitial implants in other areas of the body) to maintain the central cervix doses needed for cure. Studies of intensity-modulated radiotherapy (IMRT) versus brachytherapy show that external beam radiotherapy (EBRT) techniques cannot deliver the high-dose regions that are required for tumor eradication. Thus, brachytherapy remains a necessary component of treatment.

Because of the anatomy of the pelvis, the bladder and rectum always receive a proportion of the radiation dose. This dose varies according to physiological variations (e.g., the bladder dose may vary according to the extent of bladder filling, which may also affect the amount of small bowel in the field). The traditional ICRU reference points have been widely used in gynecological brachytherapy since their inception. However, in the era of CT- and MRI-based gynecological brachytherapy treatment planning, it has been shown in cervical cancer brachytherapy that the ICRU reference points do not provide a good surrogate for normal tissue dose evaluation in the pelvis. The GEC/ESTRO (Groupe Européen de Curiethérapie/European Society for Therapeutic Radiation Oncology) and American Brachytherapy Society ( ABS) recommendations for normal tissue dose evaluation in cervical cancer based on CT- or MRI-based treatment planning allow a much more accurate determination of the doses received by the bladder and the rectum during cervical tandem and ring brachytherapy. This allows not only better prediction of late effects but also dose conformality using HDR optimization to ensure clinical target volume (CTV) coverage while minimizing normal tissue irradiation. Although devised for cervical brachytherapy dosimetry, these recommendations are generally used for evaluation of treatment plans in all areas of gynecological brachytherapy.

Endometrial Cancer

Brachytherapy for the management of endometrial carcinoma was first described by Heyman in 1935, before the routine use of hysterectomy for uterine cancer. Endometrial cancer is the most common gynecological malignancy in the United States and the incidence is predicted to rise as obesity rates increase. Fortunately, the majority of patients with endometrial cancer are caught at an early stage because of vaginal discharge and bleeding. The use of radiation alone has now evolved; the primary treatment for endometrial cancer is surgery, total abdominal hysterectomy (TAH), and bilateral salpingo-oophorectomy (BSO).

Vaginal cylinder brachytherapy can be used in the treatment of selected gynecological malignancies. It may be indicated as adjuvant treatment following hysterectomy or for vaginal recurrence of gynecological cancer in selected patients. The majority of patients receiving adjuvant radiotherapy will have EBRT to the whole pelvis followed by a fractionated course of brachytherapy. The use of pelvic radiotherapy in selected stage I patients has been examined in randomized trials and a Cochrane meta-analysis. The three main trials, including PORTEC and GOG 99, showed that the addition of pelvic radiotherapy to surgery resulted in significantly lower rates of local relapse but no difference in overall survival (OS). The lack of a difference in OS may be because these patients already have a low risk of relapse and the sample sizes of the trials may be too low to accurately assess OS, especially in view of high rates of intercurrent illness in this patient population. Also, salvage radiotherapy to the vagina in the event of relapse is generally successful. The Cochrane meta-analysis found that the number of patients needed to treat to prevent one local recurrence was 16.7. In patients with multiple high-risk factors, there was a trend toward improved OS with pelvic radiotherapy.

The most common site of relapse in early-stage endometrial cancer following surgery alone is the vaginal vault. Adjuvant primary vaginal vault irradiation has been shown to decrease the incidence of vaginal apex recurrence in endometrial cancer from 12% to 15% to as low as 0% in selected patients, although it has no impact on OS. Selected patients may have adjuvant vaginal cylinder brachytherapy monotherapy (e.g., patients with a well-differentiated adenocarcinoma of the endometrium with myometrial invasion greater than 50%, which gives similar regional control rates to pelvic EBRT with significantly less toxicity). The use of HDR vaginal cylinder brachytherapy is well established. The role of pelvic lymphadenectomy and postoperative radiotherapy in that setting is a controversial and less well-defined area.

Vaginal vault brachytherapy can be administered using many different applicators. The most commonly used applicator is a single-channel cylinder that comes in a variety of diameters chosen according to patient anatomy and comfort ( Fig. 20.4 ). HDR afterloading has become increasingly common for vaginal cylinder brachytherapy, with no increase in morbidity or local control rates seen in retrospective analysis. The target for vaginal vault brachytherapy is the vaginal mucosa and operative scar. Ninety percent of recurrences occur at the vaginal vault and 10% in the distal vagina; therefore, in the majority of cases, the upper third to half of the vagina is treated. This decreases the morbidity associated with treating the whole vagina, such as vaginal dryness or shortening. Brachytherapy can be prescribed at the cylinder surface or at 5 mm into tissue, a depth that approximates the vaginal lymphatics.

The calculated conversion of LDR dose to fractionated HDR dose is an area of considerable variation between investigators, with fractionation schemes chosen as much because of the availability of local resources as radiobiological parameters. For HDR to be radiobiologically equivalent to LDR, the dose per fraction should be kept as low as is practically possible, usually requiring the total dose to be split into several fractions. The most common endometrial cancer HDR postoperative vaginal vault brachytherapy fractionation schedule in the United States in 2014 was 15 Gy in three fractions when given with EBRT and 21 Gy in three fractions when brachytherapy alone was used, both prescribed at 0.5 cm from the cylinder surface. The dose and fractionation of HDR administered is closely correlated with local control and late complications in gynecological brachytherapy. Sorbe et al. showed equivalent locoregional recurrence rates when treating the vaginal vault with HDR brachytherapy alone, randomizing to a schedule of 15 Gy in 6 fractions or 30 Gy in 6 fractions at 0.5 cm deep from the cylinder surface over 8 days. However, there were much lower rates of late vaginal morbidity in the lower-dose-per-fraction group. The biological effects increase faster with an increasing dose per fraction in late-reacting than in early-reacting normal tissue. Therefore, a small dose per fraction in HDR may be associated with a lower risk of late complications and a better therapeutic ratio provided that overall treatment time is not overly protracted. Vaginal vault brachytherapy can also be used to treat other gynecological malignancies, such as postoperative early-stage cervical cancer or early-stage vaginal cancer.

For patients with greater than 1-cm residual disease at the vaginal vault at the time of brachytherapy, an interstitial applicator should be used for the boost treatment. There are commercially available vaginal cylinders with interstitial needles integrated within them; alternatively, a full interstitial template should be used. The central dose heterogeneity associated with interstitial cervical cancer implants is not as easily achieved in this situation because of the lack of a uterus ( Fig. 20.5 ).

As endometrial carcinoma is linked to obesity and hypertension, some patients have medical comorbidities that preclude surgery; for those, radiotherapy may be the definitive treatment of choice. In this group, treatment is delivered via intracavitary uterine brachytherapy applicators with or without EBRT. A variety of brachytherapy techniques have been described, including Heyman capsules and double-lumen intrauterine catheters, with acceptable rates of OS in this group of patients with high levels of intercurrent illness. Initial experiences used LDR brachytherapy with applicator insertion under anesthesia and the patient immobilized during the treatment for several days. Immobilization reduces the risk of complications such as applicator movement or uterine perforation, but the risk of morbidity—such as deep venous thrombosis and decubitus ulcers—increases. Retrospective analysis has shown similar disease control comparing LDR and HDR remote afterloading brachytherapy in inoperable disease. HDR carries the advantage over LDR in patients with significant comorbidities with greatly reduced treatment times, from several days to multiple fractions lasting several minutes. Various series have reported the use of different applicators, showing that multiple channels are generally preferable to a single tandem channel and that 3D planning achieves better target coverage while still sparing the surrounding normal structures, particularly the rectum, to tolerable doses.