Breast Cancer Media Teleconference

Shortcomings of the New Study on Breast Cancer Brachytherapy (APBI): What Women Need to Know Now

On December 13, 2011, four of the world’s leading clinical researchers in breast brachytherapy gathered to provide statements and discuss a controversial new study on APBI presented at the 2011 San Antonio Breast Cancer Symposium.

• Robert Kuske, MD, (Scottsdale, AZ) Co-Principal Investigator, NSABP B-39 study comparing five-day APBI to six-week whole breast irradiation
• Peter D. Beitsch, MD, FACS, (Dallas, TX) Co-Principal Investigator of the American Society of Breast Surgeons’ MammoSite Registry
• Jayant Vaidya, MD, (London, U.K.), pioneer of targeted intraoperative radiotherapy (IORT)
• Rakesh Patel, MD, (Pleasanton, CA), Chairman, American Brachytherapy Society

Stream audio of teleconference

The study was based on Medicare billing claims for more than 130,000 patients over the age of 66 who were diagnosed with early stage breast cancer between 2000 and 2007 and received a lumpectomy and radiation.

Many members of the medical community have spoken out against the study since it was presented. In particular, many physicians object to mastectomy being considered a validated surrogate for local failure, contending that there are many indications for mastectomy unrelated to APBI, such as a new primary cancer or elsewhere failure, and that claims data do not provide sufficient clinical information to draw such conclusions. In addition, the study claimed brachytherapy was associated with higher rates of infection and increased toxicity which is contrary to results of several published clinical trials on brachytherapy.

Read statements of concern from the major medical societies involved in the research and use of APBI – American Society of Breast Surgeons, American Brachytherapy Society (PDF) and American Society of Radiation Oncology.

MD’s Criticize Breast Brachytherapy Study

A controversial study on breast brachytherapy (APBI) presented last week at the San Antionio Breast Cancer Symposium has prompted deep concern among APBI experts. They worry that breast cancer patients who are good candidates for APBI modalities such as SAVI, MammoSite and IORT will be scared off the therapy, by what the experts say is an inaccurate and misleading study.

Below are statements by three of these internationally know experts, prepared for a Dec. 13, 2011 teleconference they organized to challenge the study findings.

“Shortcomings of the New Study on Breast Cancer

Brachytherapy (APBI): What Women Need to Know Now”

  Robert Kuske, MD, FAACE:

 — Co-Principal Investigator, NSABP B-39 study comparing five-day APBI to six-week whole breast irradiation.

Partial breast irradiation (PBI) was begun in New Orleans in 1991 by myself and colleagues at the Ochsner Clinic, and has been one of the most studied treatments for breast cancer over the past 20 years.  Numerous publications have shown PBI to be safe and effective for select early stage breast cancer patients. As a result of promising phase 2 clinical trials and two favorable randomized prospective clinical trials (scientifically the “Gold Standard”), there has been growing interest in using PBI. Accelerated PBI (APBI) treats only the part of the breast affected by cancer and the treatment time is decreased from several weeks to four or five days. For decades, whole-breast irradiation (WBI), where radiation is delivered every day for five to eight weeks, has been the standard treatment for patients with early breast cancer treated with breast conserving surgery.

APBI has several benefits, including a decreased overall treatment time and a decrease in the radiation delivered to healthy tissue and adjacent organs.  To document its long-term safety and effectiveness compared to WBI, we await the results of the other 7 randomized trials comparing APBI with WBI.

I am concerned about the potential misinterpretation of data presented last week at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium regarding breast cancer patients who received brachytherapy, or accelerated partial breast irradiation (APBI). These data have serious limitations, and should not influence current treatment recommendations for women with early stage breast cancer fitting current eligibility criteria for PBI.

This study, based on Medicare claims data, demonstrated a small 1.8% increase in the rate of mastectomies in patients treated with APBI compared with those treated with conventional whole breast external beam irradiation. Note that the rate of documented recurrences of breast cancer after treatment is not reported.  In either case the rate of mastectomy is still very low (2.2 to 4%), and should be contrasted with the 35 to 40% recurrence rate after lumpectomy without any radiotherapy.

The data presented in San Antonio was drawn from records of patients varying risk factors and stage treated between 2000 and 2007. Doctors choose treatments for their patients based on cancer extent, grade, surgical margins, and other factors such as obesity, diabetes, and age.  This study failed to take these important tumor and patient issues into account, and is therefore biased. This study is a good example of why it is important to be selective in choosing which patients receive the accelerated treatment.

The PBI treatment given in this study is an antiquated balloon catheter with a single channel. Since that time, technology has dramatically improved including the use of newer multichannel applicators with tighter dose constraints. The side effects and toxicity seen with these modern technological advances are far better than the results presented in this study.

This study should encourage enrollment in clinical trials, especially NSABP B-39/RTOG 0413, a National Cancer Institute-sponsored, randomized prospective phase 3 trial. In the meantime, doctors and patients should not limit their options, and should continue to consider a 5-day alternative to conventional 6-7 weeks of whole breast irradiation to conserve the breast.

Peter Beitsch, MD, FACS:

Co-Principal Investigator of the American Society of Breast Surgeons’ MammoSite Registry.

The study presented by at the San Antonio Breast Cancer Symposium 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.

Jayant Vaidya, MD:

— Pioneer of targeted intraoperative radiotherapy (IORT).

We have performed a prospective randomized phase III trial, which is considered the highest level of scientific evidence.

We have shown with the TARGIT approach (risk-adapted partial breast radiotherapy with a single dose of radiotherapy during breast conserving surgery) that the local recurrence rate is very low (about 1% after 4 years). This rate is non-inferior to the standard approach, which was used in half of the more than 2000 patients.

This supports the concept of PBI in selected (e.g., older) patients with small tumors.

Also important was that the toxicity was not higher with the new approach. The rates of clinically relevant toxicity were about 3% in both treatment arms.  Toxicity is highly dependent on how radiation is delivered, i.e. treatment device, dose, dose rate, fractionation and target volume concept.

– End –

Breast Cancer Alert: Teleconference on 12/13

Shortcomings & Patient Concerns re: New Study of Breast Brachytherapy (APBI) –

What Women Need to Know Now

Tuesday, Dec. 13, 2011

Noon EST

Call-in number:  1-480-629-9712

Please join us via teleconference to hear statements and discussion by four of the world’s leading clinical researchers in breast brachytherapy (accelerated partial breast irradiation, or APBI).

These experts will highlight their concerns about a controversial — and potentially misleading — new study on APBI presented at last week’s San Antonio Breast Cancer Symposium. They will also provide perspective on what women need to know now about breast cancer radiation therapy.

The teleconference will feature:

Robert Kuske, MD, (Phoenix) Co-Principal Investigator, NSABP B-39 study comparing five-day APBI to six-week whole breast irradiation

Peter D. Beitsch, MD, (Dallas) Co-Principal Investigator of the American Society of Breast Surgeons’ MammoSite Registry

Jayant Viadya, MD, (London, U.K.), pioneer of targeted intraoperative radiotherapy (IORT)

Rakesh Patel, MD, (Pleasanton, Ca.), Chairman, American Brachytherapy Society

This event is open to the first 50 participants, including media and other interested parties.

(Note to media: To ensure your place on the call, please contact Liz Dowling, tel. 415-388-2794;

Problems with New Breast Cancer Radiation Study

There’s plenty of controversy about – and disagreement with – a new study from MD Anderson (MDA). One expert MD even said the study’s flaws were not trivial, but “huge.”

The study said women who got an older form of breast brachytherapy appear to have slightly higher rates of complications and subsequent mastectomy. Presented at this week’s San Antonio Breast Cancer Symposium, it was a “look-back” at Medicare records.

The MDA conclusions have prompted unusually strenuous objections from physicians who support and perform breast brachytherapy.

Breast brachytherapy, a form of accelerated partial breast irradiation (APBI), is increasingly popular because of its clinical efficacy for appropriate patients, and because it takes just 5 days.

By comparison, the standard course of external-beam, whole-breast irradiation (WBI) takes six or seven weeks. Many early-stage breast cancer patients increasingly express a preference for the far more convenient approach of APBI.

Follow-up radiation is recommended for women who have a lumpectomy as part of breast-conservation therapy. APBI now accounts for an estimated 13% of patients undergoing treatment in 2007, according to MDA’s Dr. Benjamin D. Smith, lead author of the study.

But are the study’s conclusions valid? And what are doctors saying to their patients about breast cancer treatment – especially given that the study data covers a period before more sophisticated APBI became available? (After all, even MD Anderson isn’t changing the way it offers APBI.)

“Criticism of the study surfaced almost immediately,” noted the respected radiology website “One critique was that the study is based on an analysis of Medicare billing codes rather than actual clinical outcomes.” Medicare claims data is often not a reliable measure of clinical effectiveness.

Also weighing in was the American Society of Breast Surgeons, which represents physicians who place the catheters that deliver breast brachytherapy.

ASBrS maintains a registry of 1440 patients treated by APBI with the balloon catheter device through 2004. It statement said numerous published studies have shown:

— A 5-year local cancer-recurrence rate of <5%, comparable to that of WBI;

— A low rate of other complications with APBI; and

— Good or excellent cosmetic results in approximately 90% of patients.

ASBrS noted that several randomized and nonrandomized studies using another technique of APBI — multiple interstitial catheters — have also seen rates of local cancer recurrence comparable to WBI.

For the record, Dowling & Dennis represents a company that makes one of those multiple interstitial catheters. It’s called SAVI – and it was developed to address the shortcomings of earlier brachytherapy technology, the one examined in the MDA study.

For more information on the experiences of women who’ve had SAVI treatment, see SAVI Sisters. Study data on SAVI is available here. In particular see the peer-reviewed, published results in the respected Red Journal (abstract available here.)

Other concerns about the MD Anderson study include:

— “Patients in this study received antiquated technology,” according to Robert Kuske, M.D., the principal investigator in a landmark trial comparing breast brachytherapy to traditional WBI. “Single-lumen balloons are being replaced with newer multichannel devices that allow much greater control of the radiation dose received by skin or ribs.”

— Said Dr. Frank Vicini, “All this study tells us is that when billing codes are analyzed, there appear to be differences in outcomes based upon billing-code surrogates for clinical outcomes. You can’t turn something nonclinical into clinical.”

Dr. Vicini is a Michigan radiation oncologist who publishes outcomes data comparing 199 APBI patients to 199 patients getting conventional treatment.

“Although the authors acknowledge the flaws in their study, these are not trivial,” he told AuntMinnie. “In my opinion, they are huge.”

So how should women and their families regard the controversial new study?

In urging breast cancer patients to participate in clinical studies when possible, the American Society of Breast Surgeons had this to say:

“The evidence in the MD Anderson study should be considered in pre-surgical counseling — but is not strong enough to preclude the use of APBI in properly selected patients.”