Brachytherapy

"Internal" radiation or brachytherapy involves use of a variety of radioactive isotopes which are placed inside or near the tumor/cancer. By doing so, radiation does not have to go through the normal tissue between an external source and the target of radiation. Depending on whether the radioactive isotope is placed permanently or used temporarily, brachytherapy is categorized into two categories of permanent and temporary.

The most common form of permanent brachytherapy is prostate seed implant. In this form of treatment either Palladium (Pd-103) or Iodine (I-125) seeds are implanted inside the prostate. These seeds would irradiate the prostate gland and the cancer inside it as long as they are radioactive but eventually become inert.

Depending on the strength and therefore speed of delivery of radiation, temporary brachytherapy is categorized into Low Dose Rate and High Dose Rate brachytherapy. The most common example of temporary brachytherapy is the use of either Low Dose Rate (LDR) or High Dose Rate (HDR) forms of brachytherapy for the treatment of gynecological cancers specifically cervical and endometrial cancer. Through special catheters either cesium-137 (LDR) or iridium-192 (HDR) would be inserted nearby the tumor. During the period of time when the catheters remain in area, the prescribed dose of radiation would be delivered to the target. This would take about 48 hours in LDR but only a few minutes in HDR treatment.

HDR brachytherapy is also used in the treatment of breast cancer. This form of radiation for breast cancer is called Accelerated Partial Breast Irradiation or APBI. After a lumpectomy a special applicator such as Mammosite or Contura balloon catheter or a Savi applicator is placed inside the lumpectomy cavity. Using HDR technology an iridium-192 radioactive source is inserted into any of these catheters to deliver radiation to the wall of the lumpectomy cavity.

Intraluminal brachytherapy is also used for the treatment of endobronchial tumors, esophageal cancer and cancers of biliary tract. Other forms of temporary brachytherapy include radioactive eye plaque in treatment of choroidal melanoma and Strontium-90 applicators for treatment of pterygium.

The duration of radiation treatments are also determined by the type and stage of the courses. Before prescribing any dose of radiation, a radiation oncologist has to first determine what the intention of the treatment would be. Treatment intent is either palliative or definitive.

Palliative treatment are usually given either to palliate pain, remove compression of tumor on a vital organ such as spinal cord, preventing fracture if the cancer has spread to a weigh-bearing bone, or in the case of brain metastasis to relieve the life-threatening pressure inside the brain. Palliative treatments are often given in short courses of 2-3 weeks not only because the radiation dose per individual treatments (aka fractions) is usually higher but also because the total dose of radiation is lower. Palliative radiation is often used stage IV. That is when the cancer has spread to other organs and even though it might be treatable, it is not curable.

Definitive treatment is given when, based on the stage of the cancer, statistically there is a chance for its cure (i.e. stage I-III). Depending on the type of cancer, definitive radiation can take up to 9 weeks not only because the radiation dose per individual treatments (aka fractions) is usually lower but also because the total dose of radiation is higher. Definitive treatments are given to the primary site of cancer (i.e. original site where the cancer started).

Radiation is normally given five days a week Monday through Friday. In some instances twice a day radiation may be recommended. In this case the two treatments are at least six hours apart. How long each individual treatment would take depends on many factors including the dose per fraction, the number of fields used to treat a target, the technology used and the energy and form of radiation.

Brachytherapy (aka "internal radiation") is usually given in much fewer number of treatments. For example prostate seed implant requires one procedure to place the seeds in the prostate. In treatment of gynecological cancers depending on whether Low Dose Radiation (LDR) or High Dose Rate (HDR) radiation is used anywhere between 2 to 6 treatments often one to two weeks apart is given. In a similar manner systemic radiation, in the form of an injection or oral intake, would require much fewer number of treatments. For example treatment of thyroid cancer using I-131 often requires only one treatment.

Balloon radiotherapy for breast cancer, also known as intracavitary brachytherapy, can deliver a focused dose of radiation to part of the breast. The standard since the 1980s has been whole breast radiation therapy given over a period of a few weeks. With the balloon placed by the surgeon, radiation can be delivered twice a day for ten treatments to make treatment more focused and convenient.

This is one form of accelerated partial breast irradiation, or APBI. This technique is investigational but promising enough that it's reasonable to consider as an alternative to whole breast radiation therapy. Depending upon how conservative you are regarding medical evidence, it may be best done only on a clinical trial or there are guidelines for treatment off protocol in selected circumstances, which I have answered on TalkAboutHealth before: http://bit.ly/mZ2Fdg

I offer this treatment to selected women but tend to favor standard whole breast radiation. There's a fair amount of hype about APBI but it's still not proven to be equally effective. I'm not sure if this is the NY Times article you meant, but I'll discuss this: http://nyti.ms/wVW62K

Recent data presented at the San Antonio Breast Cancer Symposium showed that women receiving APBI were "about twice as likely to have a mastectomy in the following five years" after treatment compared to women receiving whole breast radiation. Sounds terrible, right? I call foul on the NY Times:

1. The failure rate almost doubled; 4% vs. 2.2%. Had the NY Times presented it based upon success rate, 96% vs 97.8%, it's not news.

2. It's a retrospective, broad stroke study. There can be all sorts of bias and no ability to account for quality control in how the treatment was done for APBI.

3. Presentations at academic meetings are interesting, but it's not finalized, peer-reviewed research until it's published.

I'm conservative regarding use of APBI. Don't believe the positive hype, but I don't put too much stock in the NY Times article. I hope that answers your question!

Brachytherapy for the treatment of melanoma is used for the treatment of choroidal or uveal (intraocular) melanoma as an eye-sparing technique. It is also referred to as plaque brachytherapy and can be performed with several isotopes including Iodine 125 (125I), gold 198 (198Au), palladium 103 (103Pd), and others. Guidelines are available by the American Brachytherapy Society: http://www.eyephysics.com/PS/PS5/UserGuide/References/PDF/Red_J_Articles/AmerBrachyRec03.pdf

The presentation by Dr. Smith at the San Antonio Breast Cancer Symposium entitled 'Partial breast brachytherapy is associated with inferior effectiveness and increased toxicity compared with whole breast irradiation in older patients' has garnered a tremendous amount of print and Internet media attention. After reading the abstract (paper not in press yet), seeing the talk live in San Antonio, and discussing the study with many colleagues in breast surgery and radiation oncology, I want to try to clarify the data on APBI, and discuss the “information” in the abstract and the hyperbole in the lay press that is distressing our patients.

First and unequivocally, accelerated partial breast irradiation is a safe and effective form of treating the breast after appropriately performed lumpectomy in patients over age 45-50 with early-stage invasive (typically <3cm primaries and lymph node negative) and non-invasive breast cancer. Numerous retrospective studies and two prospective randomized studies (the gold standard) have shown no difference in survival, local-regional cancer recurrence rates and complications between APBI and whole breast irradiation (WBI). The American Society of Breast Surgeons’ MammoSite Registry has published more than 16 papers showing the safety and efficacy (comparable to WBI) of Mammosite APBI.

The San Antonio abstract and presentation were drawn from the Medicare claims-SEER database, which is a large database with cancer-patient data linked to Medicare claims data. The database is managed by the National Cancer Institute and sold to institutions to do research. The linked database has information about cancer type and treatments, but it has no specific data on margin status, prognostic factors such as estrogen receptor/progesterone receptor (ER/PR) and HER2/Neu receptor -- or even local, regional or distant recurrence.

The study stated that “subsequent mastectomy” is a “validated surrogate for local failure,” but I am unaware of any literature that states this. The “two-fold increased risk for subsequent mastectomy” is misleading and inaccurate. (It s 4.0% for APBI vs. 2.2% for WBI in their study). Both of these rates are quite small, and it is questionable whether there is any clinical significance between the two. Not emphasized but equally important are the overall survival rates for APBI vs. WBI, which were equivalent.

The study also stated that infections were higher for APBI (not surprising since it involves the insertion of one or more catheters in the breast), but there is no statement regarding severity (were the APBI patients just placed on prophylactic antibiotics and is that how an infection was defined?). Fat necrosis and breast pain were also significantly higher in the APBI group, although there is absolutely no uniform definition of what fat necrosis is nor a statement about the severity of the fat necrosis or breast pain.

Lastly, the researchers state there was a 9.6% hospitalization rate for APBI patients vs. 5.7% for WBI patients. This is puzzling since no diagnosis was given for hospitalization nor was there information on the time period over which patients were hospitalized. Was hospitalization APBI-related (doubtful) or related to first chemotherapy cycle (perhaps) or other unrelated health issues? (It’s worth noting that APBI is often used in older, sicker patients who may not be candidates for six to seven weeks of WBI).

In summary, this retrospective study of an inherently inaccurate database (no data on tumor characteristics and margin status -- both known to be significant determiners of local recurrence), with questionable outcomes (admission rate) and non-validated “surrogate endpoints” (subsequent mastectomy=local recurrence) should be looked at with appropriate skepticism in the face of 20 years of retrospective studies and two prospective randomized trials to the contrary.

Brachytherapy is radiation therapy delivered at a close distance - brachy means arm's length. Many cancers can be treated with brachytherapy including prostate cancer (implanted seeds), cervical cancer, and breast cancer. There any many techniques but most involve a shortened course (intra-operative single dose to two treatments per day for 5 days) and only treat the part of the breast at highest risk (the lumpectomy cavity). The term for this is Accelerated Partial Breast Irradiation (APBI) and is most commonly done with a device inserted into the lumpectomy cavity through a small skin nick. These devices (Contura, Mammosite Multi-Lumen, and SAVI) have multiple catheters bundled together that separate within the lumpectomy cavity (think egg beater). A small radiation seed (~size of a grain of rice) is inserted into each catheter and 'dwells' at a certain position for a certain amount of time to deliver the radiation dose prescribed by the radiation oncologist.

Let me start by saying that brachytherapy is safe and effective in properly selected patients. We have 20 years of studies that have analyzed patient outcome data and 2 prospective randomized trials (the true gold standard) that have shown that brachytherapy (accelerated partial breast irradiation [APBI]) is equally effective to whole breast irradiation (WBI).

There was a recent presentation at the San Antonio Breast Cancer Symposium from radiation oncologists from MDAnderson Cancer Center that has creasted some controversy. They retorspectively analyzed a large Medicare Claims-SEER database that showed equivalent survival rates between APBI and WBI. The controversial part of their presentation that they chose to emphasize was the slightly higher breast cancer local recurrence rate (as assessed by mastectomy rates) for APBI patients (4%) compared to WBI patients (2.2%). The difficulty with emphasizing this one point was that it struck fear in many patients. Frankly, both rates are very low and acceptible but to make a 'big deal' out of this clinically very small difference is unfair to APBI.

Brachytherapy is a more inclusive name for radiation that is delivered at a 'short distance' (the name 'brachy' means arm's length). Brachytherapy techniques include the Mammosite balloon technique. Mammosite is a balloon with a single catheter running down the middle. http://www.mammosite.com/ A small radiation seed (about the size of a grain of rice) is then run down the catheter and stops at various positions along the way to deliver the prescribed radiation dose. Other brachytherapy techniques include using multiple catheters that pierce the skin (interstial brachytherapy - used rarely now but was the original technique pioneered by Robert Kuske, MD) and single entry/multiple catheter devices (SAVI, Mammosite Multi-Lumen, and Contura). The radiation seed goes down each catheter (just as in the single catheter Mammosite) for a set time to deliver the prescribed dose.

I feel very comfortable offering properly selected patients - accelerated partial breast irradiation (5 days instead of 6-7 weeks) usually with one of the single entry/multicatheter devices.

There is always some leeway in these criteria including discussing all radiation options with the patient but generally
age >45
tumor size < 3 cm
Margins - neg
Lymph nodes - neg

Here is the link to the American Society of Breast Surgeons Offical Statment.
https://www.breastsurgeons.org/statements/PDF_Statements/APBI.pdf

Good question. Advantages of HDR breast brachytherapy for partial breast irradiation (PBI) include shorter treatment time, radiation exposure to less normal tissue, and that may translate into fewer side effects (not yet proven). Anecdotally, external beam PBI has had an issue with rib fractures so I've leaned toward HDR for PBI, though it can occue with either.

That's a good lead-in to disadvantages. The dose each treatment is higher and given twice a day, so there is the potential for higher injury to that more focused area of tissue. The other issue is concern that by not irradiating the entire breast, some cancer cells might not be treated and lead to a higher risk of cancer coming back within that breast.

The conservative gold standard remains whole breast radiation because of the overall low toxicity and highly effective results to prevent cancer recurrence. The strongest current argument for HDR PBI is convenience, and many doctors want to wait for data from a clinical trial underway now, NSABP B-39/RTOG 0413, before being comfortable to offer it as an alternative standard option.

The use of radiation therapy has been a standard treatment option for women undergoing lumpectomy since publication of NSABP B-06, a clinical trial conducted about 30 years ago. At that time external beam radiation (also called teletherapy) was used to treat the whole breast. While there have been some tweaks, whole breast radiation therapy remains the current evidence-based gold standard.

There has been interest if focusing radiation more on the surgivcal area only, the lumpectomy cavity. This is called partial breast irradiation and is currently under study, though promising results suggest it a reasonable option. High-dose rate brachytherapy (brachy meaning close) is a way to deliver higher doses to a more focused area.

Criteria for using HDR brachytherapy on clinical trials NSABP B-39 are listed here: http://bit.ly/r8rED1 . Currently, off study there are patients who are considered suitable based upon consensus guidelines from 2009:

Patient Factors: Women 60+ years; no BRCA mutations.
Tumor Factors: 2 cm or less invasive ductal cancer; ER+; negative margins (2mm or more); no lymphovascular invasion; no involved nodes.

Here's a link to a screenshot from the article. http://i.imgur.com/2YxQt.jpg
There are also some technical considerations.

However, not everyone agrees. William Beaumont has tended to be more willing to consider HDR brachytherapy and PBI for some patients deemed unsuitable in the 2009 consensus paper (link = http://1.usa.gov/qPYTv0). It's a controversial area that's still evolving, and varies beyond just the criteria above for each patient. So worth a long discussion if you're thinking about lumpectomy for the pros/cons of whole breast vs partial breast radiation.