Reuters: APBI unsupported and driven by reimbursements

[mainsail]

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http://news.yahoo.com/s/nm/20101211/sc_nm/us_cancer_treatment_3

 

[Gfunk6]

This article is tremendously misleading and frankly, wrong. It makes the apparent assumption that APBI = brachytherapy = Mammosite.

Our institution has been enrolling patients for years in a multi-institutional, multi-national trial of APBI vs Whole Breast RT and the results were published in Lancet this year. I think we still need long-term data over 10 years or so to definitively conclude APBI is appropriate for low risk patients. However, I think the benefit to the patient is clear. One intra-op XRT during surgery > 5 weeks of adjuvant XRT. Also, this trial is really only valid for the device that we used (Intrabeam) and cannot simply be extrapolated to other forms of APBI.

Of course, there is also a current inter-group trial (RTOG 0413) that is looking at multiple modes of APBI (multi catheter or Mammosite or EBRT) vs WB RT.

Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial.

Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eiermann W, Keshtgar M, Dewar J, Kraus-Tiefenbacher U, Sütterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M.

Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London, UK. [email protected]
Abstract
BACKGROUND: After breast-conserving surgery, 90% of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients. We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy.

METHODS: Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy with Intrabeam, we launched the TARGIT-A trial on March 24, 2000. In this prospective, randomised, non-inferiority trial, women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres in nine countries. Patients were randomly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy. Neither patients nor investigators or their teams were masked to treatment assignment. Postoperative discovery of predefined factors (eg, lobular carcinoma) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy (in an expected 15% of patients). The primary outcome was local recurrence in the conserved breast. The predefined non-inferiority margin was an absolute difference of 2.5% in the primary endpoint. All randomised patients were included in the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00983684.

FINDINGS: 1113 patients were randomly allocated to targeted intraoperative radiotherapy and 1119 were allocated to external beam radiotherapy. Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group, 854 (86%) received targeted intraoperative radiotherapy only and 142 (14%) received targeted intraoperative radiotherapy plus external beam radiotherapy. 1025 (92%) patients in the external beam radiotherapy group received the allocated treatment. At 4 years, there were six local recurrences in the intraoperative radiotherapy group and five in the external beam radiotherapy group. The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1.20% (95% CI 0.53-2.71) in the targeted intraoperative radiotherapy and 0.95% (0.39-2.31) in the external beam radiotherapy group (difference between groups 0.25%, -1.04 to 1.54; p=0.41). The frequency of any complications and major toxicity was similar in the two groups (for major toxicity, targeted intraoperative radiotherapy, 37 [3.3%] of 1113 vs external beam radiotherapy, 44 [3.9%] of 1119; p=0.44). Radiotherapy toxicity (Radiation Therapy Oncology Group grade 3) was lower in the targeted intraoperative radiotherapy group (six patients [0.5%]) than in the external beam radiotherapy group (23 patients [2.1%]; p=0.002).

INTERPRETATION: For selected patients with early breast cancer, a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks.

FUNDING: University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research (BMBF).

 

[medgator]

This article is tremendously misleading and frankly, wrong. It makes the apparent assumption that APBI = brachytherapy = Mammosite.

Hate to say it GFunk, but the article does bring up some valid points. Unfortunately, in the PP world, things are sometimes done that are reimbursement-driven rather than data-driven. Breast surgeons receive a hefty payment for placing these catheters in patients and I've definitely heard plenty of stories of patients showing up to the rad onc office for an initial consult with a mammosite/savi etc. in place.

Until long-term 10+ yr data is available (particularly from the NSABP B-39 study), following the ASTRO APBI guidelines seems like the best approach IMO.

 

[qwert]

Not a great article. $ 23K including device cost and surgical charges I presume? Completely overlooks indirect cost benefits of balloon-based brachytherapy, such return to work sooner etc.

 

[deleted4401]

I wonder what % of the 10% treated are considered to be good candidates based on consensus guidelines (I'd venture to say 95%). I think APBI is one of those things that we've actually been very good about self-policing ourselves about.

The rates for IMRT for breast are closer to ~20k, they should have mentioned that.

Eh... I'm not positive about the indirect benefits - depends on the patient. For some people, 15 min qD for 6 weeks means they can still get to work. 20 min BID for a week may cause people take vaca days for a week.

Kind of a dumb article, though, I agree...

 

[G'ville Nole]

I agree with Simul that our self-policing seems pretty good. I'm sure there are some "Mammosite factories" out there, but I'd put our percentage of Mammosite/conventional tangents at 5-10%/90-95%.

I don't know if this was published to voice some anti-Mammosite sentiment, but as GFunk noted, there is more to APBI than just Mammosite. While the 5 year numbers for Mammosite are just coming to light over the last 2 years or so, we do have 10-12 year data for interstitial APBI, as well as 5 year data from a randomized trial (http://www.ncbi.nlm.nih.gov/pubmed/17531400), all showing comparable cancer outcomes and cosmesis to conventional therapy. I'm not sure if Dr. Sher is willfully ignoring or ignorant of these studies when he states that there is no data on APBI, but neither possibility reflects well upon him. If he's speaking only of Mammosite, fair enough, but it's wrong to paint other modalities such as interstitial/intra-op with the same brush.

As to whether we require a mountain of 10 year data to offer APBI outside a clinical trial, the longer term series out there don't see a substantial difference in LR from years 5-10 over that which is observed in the EBCTCG. Call me a cowboy, but I'm OK w/ using the ASTRO criteria and offering it to appropriately selected patients.

 

[Palex80]

For some people, 15 min qD for 6 weeks means they can still get to work. 20 min BID for a week may cause people take vaca days for a week.

Plus you don't necessarily need 6 weeks if you use a hypofractionated WBRT schedule. The START-data is quite good and we offer 3-4 weeks of WBRT to our older patients, provided they don't have very large breasts.

 

[medgator]

Plus you don't necessarily need 6 weeks if you use a hypofractionated WBRT schedule. The START-data is quite good and we offer 3-4 weeks of WBRT to our older patients, provided they don't have very large breasts.

Yeah, there is definitely good LT data with hypoFx. I think the big question for some is how do we integrate the boost into those regimens (or whether pts who would be eligible for hypoFx should get a boost at all...)

 

[medgator]

I agree with Simul that our self-policing seems pretty good. I'm sure there are some "Mammosite factories" out there, but I'd put our percentage of Mammosite/conventional tangents at 5-10%/90-95%.

Definitely true in my practice as well; however, there are those notorious surgeons and questionable device reps out there unfortunately...

As to whether we require a mountain of 10 year data to offer APBI outside a clinical trial, the longer term series out there don't see a substantial difference in LR from years 5-10 over that which is observed in the EBCTCG. Call me a cowboy, but I'm OK w/ using the ASTRO criteria and offering it to appropriately selected patients.

Agreed. The ASTRO guidelines are pretty conservative (to a fault, if you talk to the pro-APBI folks). Kuske from the Arizona Breast Ca group give his 2 cents on the matter last year at ASTRO or ACRO, can't remember.

 

[Wallachia]

Plus you don't necessarily need 6 weeks if you use a hypofractionated WBRT schedule. The START-data is quite good and we offer 3-4 weeks of WBRT to our older patients, provided they don't have very large breasts.

also can omit xrt in selected low risk elderly

 

[qwert]

START B trial (Lancet 2008) has already answered your question. Do electron boost 10Gy/5fx if indicated.

Yeah, there is definitely good LT data with hypoFx. I think the big question for some is how do we integrate the boost into those regimens (or whether pts who would be eligible for hypoFx should get a boost at all...)

 

[qwert]

I presume you're basing this recommendation on CALGB C9343 (Hughes et al). In that case, you need to consent patients for increased risk of an in-breast failure.

also can omit xrt in selected low risk elderly

 

[Gfunk6]

I presume you're basing this recommendation on CALGB C9343 (Hughes et al). In that case, you need to consent patients for increased risk of an in-breast failure.

True, but there was no statistical difference in salvage mastectomies between the two arms.

 

[medgator]

START B trial (Lancet 2008) has already answered your question. Do electron boost 10Gy/5fx if indicated.

Not enough long-term F/U IMO and only 40% or so received the boost. I'd be cautious in younger women with >10 yr life expectancy.

From the Lancet 2008 study:

A median follow-up of 5 years is too short to allow assessment of all the potential late normal tissue effects such as cardiac damage. Follow-up of all women within the trial is continuing in order to assess the long-term effects of the fractionation schedules

and the ASTRO task force isn't too clear on the issue either:

http://www.astro.org/Research/CommentForm/documents/FractionationDraft.pdf

When a boost is indicated, there was lack of consensus regarding the appropriateness of HF-WBI.

There is limited evidence from prospective randomized trials to define the toxicity and efficacy of a tumor-bed boost in patients treated with HF-WBI

Given the limitations of these data, the task force was unable to reach consensus on the integration of a tumor-bed boost and HF-WBI in clinical practice.

 

[qwert]

That's true.
Important consideration: these results were obtained on a trial (rigorous follow up). Elderly in general population are less likely to be compliant with f/u exams.

True, but there was no statistical difference in salvage mastectomies between the two arms.

 

[Palex80]

I don't know if any of you have access to SpringerLink, but there's a good article on APBI in the December issue of "Strahlentherapie und Onkologie":

http://www.springerlink.com/content/611479tg55585238/

 

[seper]

Here's an important new study on withholding WBRT in elderly:
Effectiveness of radiation for prevention of mastectomy in older breast cancer patients treated with conservative surgery.
http://www.ncbi.nlm.nih.gov/pubmed?term=22890779

True, but there was no statistical difference in salvage mastectomies between the two arms.

 

[seper]

1. It's true that a retrospective study constitutes a lower level of evidence than a prospective randomized trial, by definition. 2. Accuracy of recording radiation therapy in the linked SEER-Medicare data has been studied and reported, and it's very accurate. 3. To dispute the fact that in a community setting, omission of RT causes more mastectomies, is very short-sighted.

 

[deleted4401]

I think the point was the CALGB did not show a statistically signficant increased mastectomy rate - http://meeting.ascopubs.org/cgi/content/abstract/28/15_suppl/507
Also, I agree that the proliferation of SEER database analyses is somewhat unnerving. Although hypothesis generating, these papers should not be used to guide clinical judgement. They just don't have enough information as compared to large institutional series. It's rampant speculation from a bunch of incoherent data from multiple community and academic centers. You can't put together chicken **** and expect to get chicken salad...

 

[medgator]

I think the point was the CALGB did not show a statistically signficant increased mastectomy rate - http://meeting.ascopubs.org/cgi/content/abstract/28/15_suppl/507

It probably wasn't powered to do that, considering how low the recurrence rates are to begin with after lumpectomy in this group. The CALGB trial had 636 pts, compared to a SEER analysis looking at over 7400 patients. Yes, the study methodologies aren't the same, but the sheer numbers are.

 

[deleted4401]

It was a primary endpoint and was most certainly powered to do that.

 

[medgator]

It was a primary endpoint and was most certainly powered to do that.

Sounds like you're right.... found the original paper. If that's the case, why are people pursuing SEER studies?

http://www.nejm.org/doi/full/10.1056/NEJMoa040587#t=article

The primary study end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer–specific survival, the time to distant metastasis, and overall survival. Local or regional recurrence was defined as any recurrence in the supraclavicular, infraclavicular, and ipsilateral axillary nodes, as well as any recurrence in the ipsilateral breast.

The enrollment of 572 women over a period of 38 months was required for the study to have a statistical power of 90 percent to detect this difference, assuming a one-sided significance level of 5 percent and assuming that follow-up continued for 4 years after enrollment ended. P values and confidence intervals were determined with use of O'Brien–Fleming boundaries with a Lan–DeMets spending function on the basis of these four analysis points.

 

[seper]

Because that CALGB protocol treatment (specifically, rigorous f/u in elderly) may not be fully reproducible outside of a major center. Therefore, the hypothesis was that CALGB study results were not applicable to the general population. SEER-Medicare study supported that hypothesis. Should not withhold RT after lumpectomy based on CALGB Hughes results. Especially, since 16 fx WBRT regimen is now available.

Sounds like you're right.... found the original paper. If that's the case, why are people pursuing SEER studies?

http://www.nejm.org/doi/full/10.1056/NEJMoa040587#t=article

 

[deleted254819]

I never said that the SEER accuracy of radiation reporting was inaccurate. What I said is there is limited data to objectively look at clinical and pathologic factors that may be driving outcoems. When I commented on claims, I was referring to the fact that we dont know the ratioale for mastectomy. As someone who covers and academic center and a community practice, I don't dispute that the omission of RT increases local recurrences (CALGB, B21, etc) and therefore likely increases mastectomies as this is the standard for local recurrence. However, while i think this study is a start, I dont think that it is decisive in demonstrating the increased rates of mastectomy.

I can't speak for SEER-Medicare specifically, but certainly the inaccuracies of RT reporting in the SEER registry have been well documented
http://www.ncbi.nlm.nih.gov/pubmed/21717446

 

[medgator]

Because that CALGB protocol treatment (specifically, rigorous f/u in elderly) may not be fully reproducible outside of a major center. Therefore, the hypothesis was that CALGB study results were not applicable to the general population. SEER-Medicare study supported that hypothesis. Should not withhold RT after lumpectomy based on CALGB Hughes results. Especially, since 16 fx WBRT regimen is now available.

That's my feeling. There's a controversy, but given how many options there are outside of a standard 6-7 week course of RT which is what was studied in Hughes, it shouldn't be a black/white issue about Tx vs No Tx