Continuing Education Activity

Brachytherapy is a procedure to treat and manage cancers. It acts by placing sources containing radioactive isotopes that emit radiation for a specified distance. It can be used as monotherapy or in conjunction with other cancer management. Brachytherapy can be delivered by several means, including intraluminal, intracavitary, and multi-catheter interstitial (MIB). Sources that are permanently or temporarily implanted within the tumor are labeled as interstitial brachytherapy, while sources placed near the tumor are considered plesiotherapy. Brachytherapy is different from other forms of radiation therapy because it allows for administering higher doses of radiation, minimizing insult to surrounding organs. This activity outlines the role and treatment considerations of brachytherapy in managing patients who are undergoing cancer treatment.

Objectives:

• Identify the etiology of brachytherapy medical conditions and emergencies.
• Review the appropriate evaluation for the use of brachytherapy.
• Outline the management options for brachytherapy.
• Describe interprofessional team strategies for improving care coordination and communication to advance brachytherapy and improve outcomes.

Introduction

Brachytherapy (BT) is a radiotherapy technique where radioactive devices are inserted near tumors to safely deliver high doses of radiation to eliminate and shrink tumors. Brachy- means short distance in Greek. It was first used in 1901 by Alexandre Danlos and Paul Bloch, who received a radioactive sample from Marie Sklodowska Curie and her husband, Pierre. Danlos and Bloch were attempting to treat lupus. In 1903, Margareth A. Cleaves first used brachytherapy to treat cervical cancer. Since these initial brachytherapy procedures, this technique has changed the treatment approach for breast, cervical, and prostate cancer. Brachytherapy is different from other forms of radiation therapy because it allows for administering higher doses of radiation, minimizing insult to surrounding organs.

Function

Function

Brachytherapy can be delivered by several means, including intraluminal, intracavitary, and multi-catheter interstitial (MIB). Sources that are permanently or temporarily implanted within the tumor are labeled as interstitial brachytherapy, while sources placed near the tumor are considered plesiotherapy.

Equipment

Depending on the type of implantation performed, certain types of delivery equipment will be required. After-loading technology made it easier and safer to deliver radioactive isotopes without exposing the staff to excessive amounts of radiation. Manual after-loaders are typically used in low-dose-rate brachytherapy with low-energy radioisotopes. The most well-known is the Mick ® Applicator, used for interstitial permanent seed implantation for prostate brachytherapy. It allows for the precise placement of loose seeds into the prostate.

Remote afterloading is commonly used for high-dose-rate brachytherapy with high-energy radioisotopes. A remote afterloader consists of a shielded safe where the high-activity radioactive source resides. They require a dedicated shielded room with audio/visual surveillance. The source is connected to a super elastic nickel-titanium wire that allows it to negotiate curved pathways without getting stuck. The wire is attached to a stepper motor which allows the source to allow the source to be advanced by a fixed distance and predefined dwell times with an accuracy of 1 mm. The source can travel at a maximum speed of 50 cm/second and dwell for as little as 0.1 seconds. The afterloader also contains several indexed channels that can accommodate multiple transfer tubes to the applicator. The source can exit any channel as the control console dictates outside the room. This allows the staff to deliver treatment without incurring high dose rate exposure. It has widespread use in brachytherapy-capable departments and can be used for several disease sites. Remote afterloading has resulted in a substantial reduction of staff radiation exposure.[1]

Applicators

Applicators are designed to house the radioactive isotope during treatment. They can be engineered for specific clinical scenarios or custom-made. Below is a list of applicators that may be utilized, but it is by no means exhaustive.

Vaginal Cylinder

One of the simplest applicators is the vaginal cylinder used for uterine cancer or post-operative patients with cervical cancer. It is essentially a long tube with varying diameters based on the patient's anatomy. It has a channel in the central part of the tube, allowing for the introduction of a radioactive seed from a high-dose radiation (HDR) afterloader to be used. There are also multichannel cylinders that allow for more sculpting of the dose.

Tandem and Ring/Ovoid

Other radiation applicators include the tandem and ring or tandem and ovoid, which are used in intact cervical cancer cases. The tandem is inserted in the cervical canal and uterus while the ovoid or ring surrounds the fornices. Radiation can be delivered using high or low dose rates. 

"Y"-Applicator

The Rotte-Y-applicator consists of two divergent catheters inserted into the uterine cavity. It is most often used in the treatment of medically inoperable endometrial cancer.

Valencia Applicator

Valencia applicators are used in the treatment of skin cancers. They are composed of tungsten shielding and a flattening filter. They are placed over the skin tumor with a margin. It allows for a high dose rate of superficial radiation to be delivered.

Breast Brachytherapy Applicators

The most widely used intracavitary breast brachytherapy applicators include the single-channel Mammosite® and multichannel Strut Adjusted Volume Implant (SAVI ®). These allow for accelerated partial breast irradiation (APBI) in select patients with early-stage breast cancer. They allow for a high dose distribution around the surgical cavity with a margin with rapid dose falloff in the surrounding breast.

Plaque and Sheet Applicators

Plaque brachytherapy is typically utilized in the context of ocular malignancy. These are typically low-dose rate delivery and are sutured to the eye under anesthesia. The two most commonly used plaques are iodine-125 and ruthenium-106. The I-125 plaques consist of a backing made of inert metal such as gold, with I-125 seeds placed onto the wall of the plaque. Ruthenium-106 plaques are made in various sizes, with the Ru-106 electrodeposited onto a concave silver backing. The plaques are usually kept in place for several days, and the patient must remain in relative isolation for that time.

Using prefabricated radioactive sheets for low-dose-rate brachytherapy is a relatively new development. Before this, low-dose-rate meshes were used, but spacing and orientation made it difficult to maintain dose homogeneity.[2] CivaSheet ® is a unidirectional planar implant composed of a bioabsorbable polymer implanted with regularly spaced palladium-103 sources. The unidirectionality is achieved by placing gold on the opposing side of the sheet to attenuate the source to 10% of the prescribed dose.[2] These sheets can be cut to size and sutured into a tumor bed. They are easily visualized on imaging, and superficial dose delivery and unidirectional shielding allow for the protection of deeper vital tissues. They can be utilized in a variety of clinical scenarios, such as sarcomas, pancreatic cancers, pelvic wall tumors, and lung tumors.

Interstitial Needle Templates

Interstitial catheter placement can be performed alone or with the use of a template. They can be used in a wide range of clinical scenarios. This involves the placement of needles directly into the tumor, which allows for direct radiation delivery. The needles act as channels for accommodating the radioactive isotope, which dwells in the catheter for a pre-specified amount of time. Clinical applications include but are not limited to prostate cancer, penile cancer, sarcomas, gynecologic malignancies, nasal cavity tumors, oral cavity tumors, and urethral cancer. The Syed-Neblett template is used for the interstitial placement of catheters in gynecological malignancies. It consists of a rectangular template with regularly spaced openings and a central obturator that allows for the accommodation of a cylinder.

Dosing

The dosing used in brachytherapy varies based on the type of tumor being treated, radioisotope, dose rate (LDR or HDR), number of treatments planned if using HDR, and timing (adjuvant or definitive). Please consult individual disease articles for more details.

Dose Rate

Brachytherapy is typically described by the rate at which the dose is delivered. Three categories have been established to categorize brachytherapy. These include high-dose-rate (HDR) brachytherapy delivered at more than 12 Gy/hour, Pulsed dose rate (PDR) delivered at 10-30 minute intervals at a rate of 0.5-1.0 Gy/hour, Medium dose rate (MDR) offered at 2-12 Gy/hour, and low dose rate (LDR) brachytherapy delivered at 0.4-2.0 Gy/hour. The advantages and disadvantages of LDR and HDR systems are listed in the table below.

Isotopes

Several radioactive isotopes may be used for brachytherapy. These isotopes are artificially manufactured using a nuclear reactor. A table of the most commonly used radioisotopes is listed in the table below. Iridium-192 is the most commonly utilized radioisotope for HDR brachytherapy. The LDR isotopes tend to have lower energy, decay by electron capture and have far lower dose rates. A list of common radioisotopes used is listed in the table below.

When using LDR brachytherapy that requires permanent implantation of loose radioactive seeds, the number of seeds must be estimated pre-operatively. This is most commonly performed for prostate cancer, but other LDR techniques, such as eye plaque brachytherapy, require it as well. Nomograms such as the Memorial dimension averaging method, as well as several others, have been used in the treatment of prostate cancer. In general, there is an inverse relationship between the dose rate and prostate volume.

Image Guided Brachytherapy and Treatment Planning Systems

With the advent of advanced computing technology, more precise dosimetry became possible with CT, MRI, or even ultrasound-based brachytherapy planning. These advances are most evident in treating breast, cervical, and prostate cancer. Computational methods have significantly changed brachytherapy planning as it allows for 3-dimensional target definition, dwell weight optimization, and generation of isodose calculation. Unlike the older systems, which used idealized geometries and heuristics, CT-based planning allows for the evaluation of dose distribution in real-time in the patient using the actual implant geometry. Despite these advances, several assumptions derived from previous systems, such as 1 cm uniform spacing, uniform loading, and implanting at the boundary of the tumor, persist.  

MRI-guided brachytherapy has established a foothold in the treatment of cervical cancer.[3] Superior tissue delineation allows for improved target accuracy and a reduction in the dose to normal structures. It can also allow for adaptive planning based on tumor response. The disadvantages of this technique are the added cost, operative time, and additional personnel required.

The use of ultrasound in the practice of brachytherapy for planning and directing needle placement is widespread. It is more cost-effective and does not result in additional radiation exposure compared to CT. Additionally, it is far less time-consuming than an MRI. Transrectal ultrasound-guided prostate brachytherapy is considered the standard imaging modality.[4] It is essential for preplanning, intraoperative planning, implantation of interstitial needles, and seed deposition. Three-dimensional reconstruction of the prostate, bladder, rectum, urethra, and interstitial needles can be accomplished with ultrasound. Modern treatment planning systems allow inverse planning to determine the optimal number and position of each seed within the prostate, given a set of dose constraints.

Before the widespread use of computerized brachytherapy planning and remote afterloading, the planning process relied on the use of several empirical systems. These were devised in an era when radium-226 was the dominant radioisotope. The most well-known systems are the Manchester system, the Quimby system, and the Paris system.

The Manchester system was devised in the 1930s by Herbert Parker and Rolston Paterson. The system's rules were designed to ensure dose homogeneity within the target by preferentially concentrating the radioactivity in the periphery of the implant. The ideal ratio of the periphery to core radioactivity varies with implant area (2:1 <25 cm, 1:1 25-100 cm, 1:2 >100 cm) with interstitial needles spaced 1 cm apart. The system is utilized for planar and volume implants. The amount of radioactivity required for the implant is dictated by the area of the planar implant or the volume. If the rules of the Manchester system are followed closely, then no more than a +/-10% deviation from the prescribed dose within the target area or volume can be expected.

The Quimby system was devised around the same time as the Manchester system. In contrast to the Manchester system, it uses equal-intensity implants distributed uniformly throughout the implant. Its origins and rules are not clearly defined, but the dose is specified 3-5mm from the periphery of the implant, with central doses 25-30% hotter than the prescription dose. Implants are spaced 1 to 2 cm apart. They can be used for planar and volume implants. The required radioactivity for the specified dose is ascertained by consulting a Quimby table expressed in milligram-hours to deliver a specified dose of 1000 cGy, and a multiplier determines the cumulative activity required. Generally, these implants tend to have a far higher central dose than the Manchester system.

In the 1960s, the Paris system was devised by introducing new iridium-192-based afterloading techniques and phasing out radium implants. This system requires the target's thickness, length, and width to be specified. The spacing is dictated by the thickness of the implant and the number of sources by the cross-sectional area. The linear density of the implant must be uniform. The prescription dose is 85% of the basal dose. The basal dose is calculated by averaging the minimum dose between adjacent equidistant sources in the transverse plane. Originally, the Paris system was only meant to address single and double-plane implants. As a result, the maximum thickness that can be treated with this system is 2.5 cm. Modifications to the Paris system are required for large-volume implants, but this is beyond the scope of the article.   

Radiobiology of Brachytherapy

Brachytherapy's advantages over conventional external beam treatments include the highly conformal, high dose rate treatment with short overall treatment times. Ionizing radiation functions by inducing single and double-strand DNA damage leading to cell death by apoptosis or mitotic catastrophe, with the most sensitive period being the G2/M phase of the cell cycle. In classical radiobiology, the tumor response to radiation is based on reoxygenation, repair, redistribution, and repopulation, dubbed "The Four Rs." The speed of these processes and the rate of dose delivery (LDR vs. HDR) dictate the range over which they occur and their relative importance. Repopulation is generally irrelevant if the treatment time is very short. Sublethal damage repair is more relevant at low dose rates as the rate of repair may be closer to the rate of DNA damage accumulation in contrast to high dose rates where the damage rate far exceeds the cell's ability to repair the DNA damage. Reoxygenation and redistribution play a small role in LDR brachytherapy and are thought to increase cell sensitivity to radiation.

The biological effects of brachytherapy can be modeled using a modified linear quadratic model (LQ model), which relates cell survival to dose. Due to the differences in dose rate, sublethal damage repair plays a more significant role in LDR than in HDR brachytherapy. LDR brachytherapy dose rates are in the range of 0.4-2 Gy/hr, and the delivery is continuous compared to HDR brachytherapy, where delivery occurs over several minutes and has a time gap of hours to days between fractions. For LDR techniques, a G function is introduced, with a value ranging from 0-1, which accounts for damage repair and reduces cell sensitivity to radiation. The G function depends on the rate of DNA repair, irradiation time, and half-time for repair. For HDR treatments, the value of G is set to 1. Some LQ models may also take into account reoxygenation and redistribution, which can increase the sensitivity to radiation.       

Despite the theoretical radiobiological differences between HDR and LDR, the two treatment approaches have demonstrated comparable clinical outcomes regarding tumor control and toxicity.

Issues of Concern

Brachytherapy is an invasive procedure. Outcomes are dependent on the skill of the provider.

Like other radiotherapy modalities, there is caution with radiating essential organs near tumor sites. If a source becomes dislodged from the patient, the team must notify the surrounding staff and place it into a lead container.

Patients require counseling that smoking can increase the prevalence of radiation side effects. Smoking can also decrease the efficacy of brachytherapy and other cancer treatments. Post brachytherapy treatment, there is an increased risk for bone fractures, including the pelvis. Patients, especially women, should be regularly assessed with bone density screening.[5]

Clinical Significance

Management of Malignancies

There are multiple clinical scenarios in which brachytherapy can be utilized. It can be used as definitive therapy alone or in conjunction with external beam radiotherapy. Several treatment guidelines exist, but the American Brachytherapy Society Guidelines provide a comprehensive overview of treatment indications, technical requirements, and current evidence for the most common disease sites.   

Gynecological Brachytherapy

Cervical Cancer

Brachytherapy in cervical cancer is an essential part of treatment. It is typically delivered as a boost with external beam radiotherapy and would be appropriate for patients with Stage IB3-IVA disease. However, brachytherapy alone may be considered for very early-stage disease in patients unable to undergo surgery. It is typically delivered using HDR, and there are several applicators that can be used depending on the clinical scenario. These include tandem and ring, tandem and ovoid, cylinder with tandem, and Syed-Neblett template. When used as a boost, the typical dosing assumes that the patient has already or will receive 45 Gy to the pelvis. Fractionation schemes include 7 Gy x 4, 6 Gy x 5, 5.5 Gy x 5, and 5 Gy x 6.[6] The goal EQD2 for total radiation should be in the range of 80-90 Gy.[6]

Treatment planning is typically CT based, although MRI planning may also be performed as it offers superior soft tissue delineation.[3] The outcomes depend on the response to therapy and the initial stage, but most contemporary studies show five-year local control rates for Stage IB-IIA at 98%, IIB at 91%, III at 75%, and IVA at 76%. Five-year overall survival was 82% for Stages I-II and 49% for Stages III-IV.[7] Complications include uterine perforation, infertility, vaginal dryness, vaginal stenosis, proctitis, rectal bleeding, urethritis, urinary tract infections, urinary incontinence, fistula formation, bladder urgency, and secondary malignancy.

Uterine Cancer

Vaginal cylinder brachytherapy has established itself as a mainstay of adjuvant treatment in patients with endometrial cancer. Adjuvant treatment of high and intermediate-risk endometrial cancer with radiotherapy has been extensively studied over several decades. Initial trials with whole pelvic radiotherapy were found to reduce the risk of local recurrence in the pelvis by approximately 10%.[8][9][8] It was noted that 73% of the recurrences in these patients occur in the vaginal cuff.[9][8] PORTEC-2 compared vaginal cuff brachytherapy to whole pelvic radiation and determined that the recurrence rates were comparable.[10] The criteria for recommending adjuvant treatment stems from the definition of high –intermediate-risk disease. The GOG-99 and PORTEC studies have differing definitions of this population but generally depend on patient age, histologic grade, deep myoinvasion (>50%), and lymphovascular involvement.[11]

The vaginal cylinder applicator is typically a single channel with various predetermined lengths and diameters (range 2.0-4.0 cm).[12] Segmented cylinders are also available and can be assembled to the required length.[12] In addition, multichannel cylinders are employed as they allow for more dosimetric control to lower bladder and rectal doses. It is recommended that the largest diameter cylinder be used for the patient to minimize air gaps and decrease vaginal wall dose.[12]

Several dose fractionation schemes can be utilized. In the adjuvant setting, the most common schemes are 7 Gy x 3 prescribed to 5 mm depth or 6 Gy x 5 to the vaginal surface. If it is used with external beam treatments, then 6 Gy x 3 or 6 Gy x 2 prescribed to the surface can be used. Although HDR is the most common, LDR can be employed as well and is typically delivered at 100 cGy/hour to the vaginal surface.[12] CT-based planning has been adopted as it allows for the cylinder to be visualized not only in relation to the bony pelvic anatomy but also to nearby organs at risk. ABS guidelines recommend treating the upper 3 to 5 cm of the vagina unless there is gross lower vaginal involvement. Complications of treatment include cuff dehiscence, vaginal stenosis, vaginal shortening, and dryness.

Medically inoperable endometrial cancer is another challenging area that may also benefit from brachytherapy. The Rotte-“Y” applicator is a two-channel applicator placed along the wall of the uterus and can be used in conjunction with external beam radiotherapy. Radiation delivery is usually performed with HDR to a dose of 20 Gy in 5 fractions when used with external beam radiation and 35 Gy in five fractions when used alone.[13] However, other fractionation schemes have been utilized.[14] The 5-year cause-specific and overall survival rates were 87% and 42%, respectively.[13] Late grade 2 or higher toxicity occurred in 13% of patients.

Breast

Accelerated partial breast radiation (APBI) allows for a shorter course of treatment with excellent rates of local control in patients with early-stage breast cancer compared to conventional external beam radiotherapy. Mammosite® and SAVI®. These applicators are implanted after the breast-conserving surgery and placed in the surgical cavity. APBI using brachytherapy, delivers a dose of 34 Gy in ten fractions given twice a day 6 hours apart. Local control rates are around 4.6% at ten years, comparable to external beam methods.[15]

The ASTRO consensus guidelines provide detailed selection criteria for appropriate APBI candidates.[16] The disadvantages of this treatment include the potential need for a second operation to implant the device, infection, and general discomfort while the device is in place. In addition, alternative delivery methods such as IMRT-based accelerated partial breast irradiation may be easier tolerated by patients.

Genitourinary Cancers

Prostate Brachytherapy

Prostate brachytherapy features prominently in the treatment of prostate cancer. It may be used as monotherapy in low and favorable intermediate-risk prostate cancer or as a boost when combined with external beam radiotherapy in high-risk disease. In addition, some centers have used brachytherapy for salvage therapy in recurrent cases. LDR and HDR modalities have both been utilized with excellent outcomes. Contraindications to prostate brachytherapy include distant metastasis, unacceptable operative risk, large prostate urethral defects, ataxia telangiectasia, absence of rectum, and limited life expectancy.[4] Relative contraindications include prostate gland size greater than 60 ccs, IPSS scores greater than 20, inflammatory bowel disease, and large median prostate lobe. 

The procedure requires the placement of interstitial needles into the prostate using a transperineal approach under trans-rectal ultrasound guidance (TRUS). Ultrasound imaging serves not only as a guide for needle placement but also as a means of treatment planning. This technique is used for both LDR and HDR brachytherapy. LDR typically uses a Mick applicator ®, which is used to manually load loose radioactive seeds in the prostate or preloaded needles with seeds attached to a ribbon. HDR uses a remote after loader in a shielded room to protect staff from higher levels of radiation exposure.

Dosing varies depending on the dose delivery technique. When using HDR, monotherapy doses include but are not limited to 9.5 Gy x 4 and 12-13.5 x 2.[17] As a boost with an external beam, these include but are not limited to 5 Gy x 4, 7 Gy x 3, 10 Gy x 2, and 15 Gy x 1.[17] Single-fraction HDR monotherapy has been explored; however, disappointing rates of biochemical control have precluded its adoption.[18] Ir-192 is the most commonly used isotope for this method of delivery. When using LDR, the dose depends not only on the treatment sequence but also on the radioisotope being used. The most commonly utilized isotope is I-125. If used as monotherapy, then the dosing ranges from 140-160 Gy. If used in combination with an external beam, the dose is typically 108-115 Gy.[17][19]. Pd-103 or Cs-131 isotopes will have different dosing depending on the clinical situation.

As monotherapy, the biochemical control rates range from 85 to 97% at five years for low and intermediate-risk prostate cancer.[17] As a boost in high-risk prostate cancer, the addition of brachytherapy to external beam radiotherapy resulted in a 15-year biochemical progression-free survival rate of 80%. However, there was no difference in overall survival.[20] No evidence has suggested that the isotope utilized or the dose rate (LDR or HDR) significantly impacts the oncologic outcomes. The quality of the implant likely plays a larger role in determining the risk of toxicity and biochemical control.

Treatment-related toxicity includes urethritis, urinary retention, erectile dysfunction, prolonged use of an indwelling catheter, and rectal urgency. Some of these symptoms will lessen with time, but certain side effects, such as erectile dysfunction, may persist. Late toxicity, such as rectal fistulas and urinary incontinence, are extremely rare.[17]

Penile Cancer

Penile cancer represents 1% of all male malignancies, with squamous cell carcinoma being the most common histology. Surgical techniques typically consist of a partial or total penectomy with or without an inguinal lymph node dissection. Penile preservation techniques are preferred due to the adverse psychological impact of a penectomy. The implant is typically an interstitial implant. Indications include T1-T3 tumor without penile shaft involvement and less than 4 cm in size. It may also be employed postoperatively if there are positive margins. This can be accomplished with PDR or LDR to a total dose of 60 Gy. The 5-year penile preservation rate was 86%, with an overall survival rate of 78%.[21] Toxicity included a 16% rate of soft tissue necrosis and a 12% rate of urethral stenosis.[21]

Urethral Cancer

Brachytherapy can be used to treat males and females with urethral cancer. Multiple techniques have been described in the literature, including interstitial implants, intracavitary, and intraluminal. The dose can be delivered with LDR to 60-70Gy over a 3-5 day period or as a boost 20-25Gy with an external beam. Seven-year overall survival was found to be 41%.[22]

Ocular Cancers

Ocular Melanoma

Vision-sparing treatments in the setting of ocular malignancies were studied extensively with the Collaborative Ocular Melanoma Study (COMS). The COMS “Medium trial” (height 2.5 - 10.0 mm and diameter less than or equal to 16 mm), which randomized patients that received enucleation or episcleral plaque brachytherapy to a dose of 85 Gy with I-125 demonstrated no statistical difference in overall survival (59% vs. 57%) or distant metastasis (17% vs. 21%).[23] There did not appear to be an increase in second malignancies.[23] Five-year local control rates range from 82 to 98%.[24] Other radioisotopes, such as ruthenium-106, are commonly used in Asian and European countries. It is valued for its steeper dose gradient and ability to spare distal eye structure.[25] Retrospective comparisons with I-125 suggest comparable disease-specific survival and overall survival.[26] Contraindications include gross extraocular extension, painful eye, and no light perception. 

Retinoblastoma

Plaque brachytherapy may also be used in retinoblastoma treatment, typically as a secondary option after failure of systemic therapy or other focal therapies.[24] Several vision-sparing focal treatments exist for retinoblastoma. Treatment with I-125 or Ru-106 plaques is acceptable. Tumors are treated to a dose of 40-50 Gy to the tumor apex over 3-5 days.[24] The indications for treatment include residual or recurrent tumors after primary treatment. Tumor size limits the apical height to 10 mm while the base measures 15mm.[24] Salvage plaque brachytherapy has excellent rates of local control ranging from 95 to 100%; however, ocular complications should be anticipated.[27] Plaque brachytherapy offers vision-sparing treatment to patients that would otherwise require enucleation.

Treatment complications include cataract formation, iritis, uveitis, retinal detachment, optic neuropathy, retinal hemorrhage, scleral necrosis, intraocular vasculopathy, painful eye, and dry eye.[24] These complications can result in worsening visual acuity and possibly the need for enucleation.

Central Nervous System Cancers

Recurrent gliomas are particularly challenging to treat as therapeutic options are limited, and the prognosis is generally poor. There are several brachytherapy options that have emerged in the last two decades to allow for additional radiation to be given for surgically operable recurrent gliomas. The GliaSite ® system is an inflatable catheter that can be inserted into a resection cavity and inflated with a solution of I-125 or Cs-131, allowed to dwell in the cavity over several days.[28] The total dose is typically 60 Gy prescribed to 1cm from the surgical cavity.[28] The median survival was 35.9 months, with a 1-year survival of 31.1%.[28] The procedure is well tolerated, but a survival benefit has not been demonstrated.[29][30] Potential candidates include those with tumors less than 4 cm in size that are roughly spherical.

GammaTile ® is a more recent development in brachytherapy. It is a permanent Cs-131 implant embedded in a resorbable collagen matrix that can be placed within a surgical cavity.[31] It delivers 120-150 Gy to the cavity and 60-80 Gy to 5 mm below the surface. There are several clinical scenarios GammaTile® may be used with, including brain metastasis, meningiomas, newly diagnosed glioblastoma, and recurrent glioblastoma.

Head and Neck Cancers

Recurrent Nasopharyngeal cancers

Nasopharyngeal cancers are typically treated with radiotherapy with or without chemotherapy. Local recurrence rates range from 3 to 7% at five years.[32][33] When they recur, the patient may require salvage surgery which can be extensive and morbid. In some cases, the tumor may not be adequately accessible for resection, and other techniques may be needed. Since the majority of these patients would have received radical radiotherapy previously, re-irradiation would need to be exceptionally conformal to minimize doses to normal structures, which likely received doses close to their tolerances. The Rotterdam Applicator, developed in the mid-nineties, is to be used with an HDR afterloader system and placed into the nasopharynx via the nasal cavity.[34] It consists of flexible silicone material forming two separate channels to deliver radiation. The doses delivered vary and include but are not limited to 36 Gy in 6 fractions once per week, 20-36 Gy over 5-9 fractions, and 51 Gy in 17 fractions delivered twice a week.[35] The locoregional recurrence-free survival at 5 and 10 years was 75.4%, and the five and 10-year overall survival was 74.3% and 53.7%.[35]

Oral Cavity Cancers

Brachytherapy has been used in the oral cavity as both a boost and a monotherapy. External beam is limited by the dose delivered to the mandible, and brachytherapy can allow for a more conformal dose. Implants are typically performed freehand with interstitial needles placed under anesthesia. The most common sites are oral tongue, lip, and floor-of-mouth tumors. It can be delivered using LDR or HDR. LDR dosing is typically given as monotherapy to 60-70 Gy or 20-35 Gy as a boost after 50 Gy of external beam radiotherapy.[36] HDR dosing is given as 21 Gy in 7 fractions as a boost after external beam radiotherapy or as monotherapy 45-60 Gy at 3-6 Gy per fraction.[36] Retrospective analysis of early-stage T1-T2 oral tongue cancers treated with 16-32 Gy of external beam and then boosted with 40-55 Gy of interstitial brachytherapy had a two-year local control rate of 92%.[37]   

Sarcoma

Brachytherapy for sarcoma treatment is typically utilized in the postoperative setting. Interstitial free needle implants are placed in the surgical bed at the time of resection. Brachytherapy in this setting carries the advantage of being able to deliver higher doses than with an external beam and can shorten treatment times. Both LDR and HDR have been used in this setting. Indications include positive margins, close margins, and local recurrence.[38] It can be used as monotherapy or a boost in addition to external beam therapy. The dosing used for adjuvant radiation is 36 Gy in 3.6 Gy/fraction twice a day with HDR or 45 Gy with LDR monotherapy. As a boost, the dose is 14-16 Gy with HDR and 16-20 Gy with LDR. While adjuvant radiotherapy does not improve overall survival, it does substantially improve local control. The 5-year local control rates are approximately 90% (Pisters et al. 1996).[39] Treatment complications include delayed wound healing, bone fracture, and chronic neuropathy.[38] There appears to be a higher rate of wound healing complications in the LDR group compared to HDR (40% vs 18%).[38]

Skin Cancers

Superficial brachytherapy is one of several treatment modalities available to treat non-melanoma skin cancers in patients who refuse or cannot undergo surgical removal. Generally, this is utilized for relatively small tumors (T1-T2) on the face or areas that would require extensive surgery to remove. Several radiation delivery devices have been introduced for superficial radiotherapy, including electron beam radiation, superficial X-rays, orthovoltage X-rays, and HDR brachytherapy. For brachytherapy, there are several applicators available, including Valencia applicators, Leipzig applicators, and Freiberg flaps that can deliver superficial radiation. Custom applicators may be made as well. More recently, HDR electronic brachytherapy has emerged that allows for HDR treatments to be delivered without the need for dedicated treatment vaults, shielding, or for radioactive isotopes. Electronic brachytherapy can treat lesions up to 5mm in thickness. However, long-term data on the efficacy of electronic surface brachytherapy is lacking.[40] Dosing ranges from 40-60 Gy, delivered once or twice per week in 3-10 fractions, depending on the type of applicator used.[41] The 5-year local control rates range from 92 to 99%.[42] Complications include skin necrosis, fibrosis, telangiectasias, chondritis, and bone necrosis.

Enhancing Healthcare Team Outcomes

Interprofessional communication is especially crucial for brachytherapy. Identifying tumors and planning the best route for administration and duration of administration requires the cooperation of many interprofessional teams. Radiologists can assist with using MRI imaging to map and locate 3-dimensional regions for the tumor. 

Nurses in oncology services are essential patient advocates.[43] They provide an additional opportunity to check dosing plans and inquire about the patient's history. Also, they can be instrumental in assuring that the patient receives a low-residue diet to reduce the frequency of bowel movements while undergoing brachytherapy.