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 the administration of higher doses of radiation, minimizing insult to surrounding organs.

Brachytherapy is provided in many different ways. It can be delivered intraluminal, intracavitary, and multi-catheter interstitial (MIB). Sources implanted within the tumor are labeled as interstitial brachytherapy, while sources placed near the tumor are labeled plesiotherapy.

The most common isotopes used in brachytherapy are:

• Iridium-192: Usually takes the shape of a corn kernel and is about the same size as a rice grain but is produced initially as a wire. It is a silver-white color with a half-life of 74 days and stable daughter products.
• Cobalt-60: A synthetic isotope that was previously reported to be ineffective as an option for radiotherapy.[1] Its half-life is 5.3 years.
• Iodine-125: Takes the shape of seeds and can be 3D printed to fit the exact specifications for the patient.[2] The half-life is 59.7 days.
• Palladium-103: This is a stable isotope of palladium with a half-life of 17 days. It has uses in both prostate cancer and choroidal cancer.[3][4]

The function of brachytherapy is to deliver prolonged and precise radiation to regions of the body while minimizing the extent of radiating unnecessary areas of the body. The radiation dose rapidly declines as the distance increases from the emitting source. The decline in radiation is known as the inverse square law.[5] The inverse square law holds true because any emission for a source will go straight out equally in all directions. As the radius increases, fewer incident radioactive photons will have exposure to a particular area. This physics translates to the relative absorbed dose of I at 0.01% when 5.26 cm from the source.

Low dose rate (LDR): THis approach is a less common means to administer brachytherapy. The dose rate for this treatment is between 0.4 to 2.0 Gy/h.[6] LDR is primarily an in-patient procedure. There has been a great success, however, with the use of LDR in the setting of prostate cancer.[7]

Pulse-dose-rate (PDR): This is a hybrid between modality that combined LRD and HDR. The pulses are between 10 and 30 minutes, with a dose range of 0.5 to 1.0 Gy/h. PDR allows for better control for placement of source and the ability to change source location while also reducing radiation risk for staff. With gynecologic cancers, a study has shown a decrease in fistulas, dysuria, and diarrhea using PDR.[8]

High dose rate (HDR): This is currently the most commonly used modality for brachytherapy. It can be administered in the outpatient setting. The dose range is usually greater than 12 Gy/h. This high dosage requires more rigorous shielding to protect staff. Large doses of radiation are administered from sources over minutes. Computers reposition sources to predetermined dwell positions. This technique allows for the maximization of isodose distribution and limited extra-tissue involvement.[9]

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

Like with 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.[10]

Management of Malignancies

Breast Cancer: Brachytherapy is commonly used in conjunction with surgical management. There is great interest in specific use after lumpectomy to minimize irradiating the entire breast. Its scope is limited to patients that do not have T3/T4 disease and are negative for nodal involvement.[11] The American Society of Radiation Oncology (ASTRO) has categorized brachytherapy candidates into three categories: Suitable, cautionary, and unsuitable. The two main ways to deliver brachytherapy are interstitial (IMB) and intracavitary (IBB).

IMB places catheters around the lumpectomy site one week after surgery and remains embedded for one week. IBB places a balloon catheter with interior channels near the surgery site. Pellets are placed inside the channels several days after surgery and are removed one week later. Less commonly, seeds can be permanently placed near the surgical site several weeks after lumpectomy. Generally, older women have less beneficial outcomes with brachytherapy compared to younger women. Single-entry multi-lumen intracavitary brachytherapy has demonstrated to have superior cosmetic outcomes when compared with external beam radiation therapy (EBRT).[12]

Gynecologic Cancer

• Cervical cancer: Brachytherapy is a common choice to boost a chemotherapeutic approach to treatment. The most common method is intracavitary brachytherapy and is a frequent choice in conjunction with EBRT. Treatment approaches divide between women who have a uterus or those who have undergone a hysterectomy. Special care is needed for those with a uterus, as this is a potential organ at risk (OAR). Cervical cancer brachytherapy in patients with a uterus is commonly performed with a tandem and ovoid (T&O) applicator. T&O is placed in the operating room under sedation. The tandem is a hollow metal tube that can house radioactive sources, and the ovoid supports the tandem by applying pressure at the outer end of the cervix. The tandem is inserted into the cervix, and, depending on the provider, a Smitt sleeve may be placed in the uterus to facilitate multiple rounds of T&O. HDR is most useful for the management of residual tumors from initial treatment. Less commonly, LDR is an option. The most common side effect is erythema and vaginal discharge with long-term side effects, including vaginal stenosis. Other long term side effects include chronic cystitis, rectal stenosis, atrophic vaginitis, and lymphedema.
• Endometrial cancer: This is one of the most common gynecologic cancers. After initial surgical treatment, vaginal cuff brachytherapy (VCB) can help to reduce the potential recurrence of the disease. The most common site of recurrence is at the vaginal cuff. VCB ae managed with single-cylinder applicators, multi-cylinder applicators, colpoplasts, and molds. Single-cylinder applicators are the most commonly used device but are prone to having air gaps between the vaginal surface. The method is limited by the vaginal introitus, which can be problematic if the vaginal apex is larger than the introitus.[13] Both HDR and LDR can be used with applicators. For HDR, the treatment takes 10 minutes, while LDR remains in the patient for several days. The most common side effect is radiation vaginitis, which can be managed with vaginal douching to reduce the development of sores. 
• Vaginal cancer: Although a relatively rare diagnosis, brachytherapy is beneficial in all cases. Concomitant MRI assists with the optimal placement of sources. The same brachytherapy techniques employed for VCB in endometrial cancer are the same ones used in vaginal cancer.[14]

Prostate Cancer

This is usually a single treatment of LDR, especially for localized prostate cancer. Research has also shown that HDR in the setting of external beam radiation reduces the likelihood of cancer reappearing when compared with single-therapy external beam radiation therapy (EBRT).[15] HDR can be especially useful if the patient has locally advanced prostate cancer staged T3 or higher. HDR is conducted by having catheters placed surgically under the guidance of ultrasound. Patients who recently have undergone transurethral resection of the prostate are not candidates for brachytherapy because of the increased likelihood the radiation will affect nearby organs.

Pancreatic Cancer

While surgical resection is the only curative treatment for this type of cancer, many providers use brachytherapy for patients who are non-surgical candidates. Brachytherapy appears to be superior to EBRT because it addresses the patient's pain while minimizing the radiation side effects.[2] There have been studies that have shown that I-seeds have been able to extend life expectancy by nine months in patients with pancreatic patients while also reducing pain.[16]

Lung Cancer

Brachytherapy augments the surgical excision of different types of lung cancers. There are limited guidelines for use in these patients. The main categories of treatment are endobronchial and interstitial. Endobronchial brachytherapy is either curative or palliative. Curative endobronchial brachytherapy is useful for cancers in patients that are not surgical candidates either through personal medical history or because their cancer in surgically inoperable. Curative cancers are confined to the larger pulmonary structures, including but not limited to bronchus and trachea. HDR-brachytherapy is preferable in these patients.

On the other hand, palliative endobronchial brachytherapy is useful in managing tumor symptoms, including dyspnea, hemoptysis, and cough. HDR is highly successful at symptomatic relief in 50 to 99% of patients.[17]

Interstitial brachytherapy is more invasive than endobronchial because it usually requires a thoracotomy. It is reserved for patients that have undergone extensive resection and need a treatment that would limit the extent of irradiation of healthy lung tissue. Both LDR and HDR have been effective modalities for interstitial brachytherapy.[18]