RFA > SBRT for early stage HCC, yeah right

[Gfunk6]

http://ascopubs.org/doi/10.1200/JCO.2017.75.3228

How the hell can you publish a retrospective study in JCO when there is a > 10-fold imbalance between the two groups!?

You have 3,600 patients in RFA group and < 300 in SBRT group. This is one of the worst cases of selection bias that I have seen. I love their conclusion that " . . . we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending local ablative therapy for localized unresectable HCC."

Garbage.

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[medgator]

Definitely reduced my opinion of jco a bit.

Just look at the data on rfa vs sbrt for nsclc. Somehow the IR guys conned the NCCN into finally including them into the footnotes

 

[Gfunk6]

One of my colleagues recently had an IR doc refuse to put in hepatic fiducials for SBRT tracking because "it's not worth [his] time" and if he was going to block procedure time for it, "[he] may as well do RFA."

 

[medgator]

One of my colleagues recently had an IR doc refuse to put in hepatic fiducials for SBRT tracking because "it's not worth [his] time" and if he was going to block procedure time for it, "[he] may as well do RFA."

Maybe see if that's something an interventional GI doc might be interested in doing...

 

[scarbrtj]

My own gestalt is that the standard deviation of tumor control probability with SBRT would be higher than RFA due to the heterogeneity of SBRT approaches (dose, especially... I know *my* dose is different than *your* dose) vs RFA approaches. And, even though I'm no statistician, I play one on TV. And when I see a 10:1 intervention-1:intervention-2 sample size retrospective study, and the 95% confidence intervals overlap... which they do in this study (5-year overall survival was 29.8%; CI 24.5% to 35.3% in the RFA group, versus 19.3%; CI 13.5% to 25.9%)... I see a trend, but lackluster evidence, statistically. Regardless the p-value. But, I'm a bit of a heretic.

 

[Ray D. Ayshun]

Not that it’s necessarily relevant, but they state that those receiving sbrt were more commonly white, which isn’t even true. Oddly, though, this doesn’t match with my experience where those referred for sbrt generally have a higher Charleston-deyo score, which is even stranger here being that the sbrt population was older. And of course, Tnm staging doesn’t account for location necessarily (And the distribution and numbers in the fibrosis comparator!). Also, didn’t see that they excluded those who were previously treated (Nvm, saw primary treatment, which makes me ven less-inclined to believe they properly captured comorbidities. When do the robust ones start with sbrt?). This is clearly an area where the subtleties necessitate an rct, which I think are currently accruing. There was no reason to publish this.

 

[littleemma]

There are a lot good NCDB studies, but this one is the one of the worst I have even seen, and on JCO!

Highly selective group of patients, 300 RFA vs 3600 SBRT. Propensity matching does not work: there are 12 matching FRA for each SBRT.

Do not know if it was ever reviewed by a radiation oncologist:
out of the 275 pt got SBRT: 60 pt got dose > 50 Gy, but fx unknown; 40 pt got brachy, dose unknown;

No control for AFP, meld score, child-pugh score.

 

[DrfluffyMD]

Just being an advocate for the IR side, let’s not lose sight of the forest. Ablative therapy, when targeting a small enough lesion, denature the biological material within the target area and as far as I am aware have similar outcome data to surgery.

One can debate the methodology, but the intuitive thought is that this is a comparison between radiation therapy (which is quite good, I am sure) and a modality that evacuate a void of living tissue that happen to encompass the tumor.

 

[Gfunk6]

Just being an advocate for the IR side, let’s not lose sight of the forest. Ablative therapy, when targeting a small enough lesion, denature the biological material within the target area and as far as I am aware have similar outcome data to surgery.

One can debate the methodology, but the intuitive thought is that this is a comparison between radiation therapy (which is quite good, I am sure) and a modality that evacuate a void of living tissue that happen to encompass the tumor.

In case you don’t know, SBRT is by definition ablative.


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[medgator]

In case you don’t know, SBRT is by definition ablative.


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Hence the alternative moniker of "SABR", which many in the field choose to refer to it as

 

[DrfluffyMD]

Hence the alternative moniker of "SABR", which many in the field choose to refer to it as

Sure. But if I understand correctly, surgery, RFA and SBRT all have different mechanism of “ablation”. Surgery take it out. RFA induce heat and coagulation/necrosis due to protein denaturing, and SBRT cause extensive DNA damage.

It seems conceivable that different method can lead to difference in outcomes.

I believe there is certainly a need to investigate this issue farther by a well designed trial. Focusing on how a journal shouldn’t publish the study in the OP to me, in my humble opinion as a trainee, is missing the forest (possible outcome differences) for the tree (indivdual methodology of that study).

 

[medgator]

Sure. But if I understand correctly, surgery, RFA and SBRT all have different mechanism of “ablation”. Surgery take it out. RFA induce heat and coagulation/necrosis due to protein denaturing, and SBRT cause extensive DNA damage.

It seems conceivable that different method can lead to difference in outcomes.

I believe there is certainly a need to investigate this issue farther by a well designed trial. Focusing on how a journal shouldn’t publish the study in the OP to me, in my humble opinion as a trainee, is missing the forest (possible outcome differences) for the tree (indivdual methodology of that study).

Sabr causes ablation afaik and has a distinctly different mechanism than conventional EBRT which induces DNA double stranded breaks to exert its effect.

Someone closer to their radbio training than me can probably explain/verify it better

The issue with RFA is how it addresses larger diameter lesions, exerting its effects inside out rather from the outside in....

 

[evilbooyaa]

Man, this is the quality of NCDB stuff that gets published in JCO nowadays?

Look at Table A2 (last page)

How do 40(14%) patients with unknown radiation dose translate to "lol definitely SBRT". 22% got < 40Gy? That's not SBRT for primary HCC. That means that for 36% of patients the dose could have been non-SBRT. Sensitivity analysis to exclude those patients and re-run the data?

One patient got brachy - clearly no QA of the database (at least from a radiation perspective) from the authors in regards to this.

I honestly don't think non-radiation oncologists should be able to write about radiation, especially in the NCDB, because they invariably have no idea about the technical differences that NCDB can routinely provide on radiation (dose, technique, etc.)

It's clear that a radiation oncologist was not involved in the review of this paper.

 

[seper]

NCDB data are inherently inaccurate; I'm surprised the JCO editor was not aware of that.

 

[littleemma]

NCDB data are inherently inaccurate; I'm surprised the JCO editor was not aware of that.

That is not necessary true. NCDB does have the inherent bias, but there are many high quality NCDB studies published on JAMA, JAMA ONC and JCO.

It totally depends on your study question, how you perform your study and how you control the variables.

This study is one the worst.

 

[DrfluffyMD]

Can someone explain to me how SBRT ablates in mechanism besides DNA damage? One of the poster alluded that SBRT does more than DNA damage.

 

[radtothebone]

Can someone explain to me how SBRT ablates in mechanism besides DNA damage? One of the poster alluded that SBRT does more than DNA damage.

The prevailing thought is that that the vascular supply to the tumor is also damaged with the ablative doses of SBRT.

http://www.rrjournal.org/doi/full/10.1667/RR2773.1?code=rrs-site

This current study is garbage. The radiation information is poor, no child-pugh, crazy imbalance. Every comparison I seen before suggest RFA is more or less equal to SBRT for local contol, with SBRT doing better on larger tumors. Local failure is not what kills these patients, and I don't think treatment toxicity is what would drive the observed survival difference.

 

[Burt Radnolds]

Can someone explain to me how SBRT ablates in mechanism besides DNA damage? One of the poster alluded that SBRT does more than DNA damage.

The thought is that there may be more than just cell kill due to tumor DNA damage, but also an effect due to vascular damage and creating an overall inhospitable environment for continued local tumor growth. These effects would also still be due to DNA damage however.

 

[seper]

I was referring to accuracy of radiotherapy ascertainment in NCDB. I'm hearing from multiple people it's 70% or so.

That is not necessary true. NCDB does have the inherent bias, but there are many high quality NCDB studies published on JAMA, JAMA ONC and JCO.

It totally depends on your study question, how you perform your study and how you control the variables.

This study is one the worst.

 

[medgator]

http://www.redjournal.org/article/S0360-3016(17)34233-5/fulltext?elsca1=etoc&amp;elsca2=email&amp;elsca3=0360-3016_20180315_100_4_&amp;elsca4=Radiology/Imaging|Radiation Oncology|Oncology

Treatment with SBRT or RFA is well tolerated and provides excellent and similar local control for intrahepatic metastases <2 cm in size. For tumors ≥2 cm in size, treatment with SBRT is associated with improved FFLP and may be the preferable treatment.

 

[DrfluffyMD]

http://www.redjournal.org/article/S0360-3016(17)34233-5/fulltext?elsca1=etoc&amp;elsca2=email&amp;elsca3=0360-3016_20180315_100_4_&amp;elsca4=Radiology/Imaging|Radiation Oncology|Oncology

Can’t access the journal. Can someone post an abstract?

 

[evilbooyaa]

Can’t access the journal. Can someone post an abstract?

It's an update of a 2015 single institution retrospective review that got into JCO

Purpose
Stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) are widely used therapies for the treatment of intrahepatic metastases; however, direct comparisons are lacking. We sought to compare outcomes for these 2 modalities.

Methods and Materials
From 2000 to 2015, 161 patients with 282 pathologically diagnosed unresectable liver metastases were treated with RFA (n = 112) or SBRT (n = 170) at a single institution. The primary outcome was freedom from local progression (FFLP). The effect of treatment and covariates on FFLP was modeled using a mixed-effects Cox model with application of inverse probability treatment weighting to adjust for potential imbalances in treatment modality.

Results
The median follow-up period was 24.6 months. Patients receiving SBRT had larger tumors than those treated with RFA (median, 2.7 cm vs 1.8 cm; P < .01). On univariate analysis, tumor size was associated with worse FFLP for RFA (hazard ratio

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; 1.57; 95% confidence interval [CI], 1.15-2.14; P < .01) but not for SBRT (HR, 1.38; 95% CI, 0.76-2.51; P = .3). The 2-year FFLP rate was 88.2% compared with 73.9%, favoring SBRT (P = .06). For tumors ≥2 cm in diameter, SBRT was associated with improved FFLP (HR, 0.28; 95% CI, 0.09-0.93; P< .01). On multivariate analysis, treatment with SBRT (HR, 0.21; 95% CI, 0.07-0.62; P = .005) and smaller tumor size (HR, 0.65; 95% CI, 0.47-0.91; P = .01) were associated with improved FFLP. The 2-year overall survival rate was 51.1%, with no difference between groups (P = .8). Grade ≥3 treatment-related toxicity was rare, with no difference between SBRT (n = 4) and RFA (n = 3).

Conclusions
Treatment with SBRT or RFA is well tolerated and provides excellent and similar local control for intrahepatic metastases <2 cm in size. For tumors ≥2 cm in size, treatment with SBRT is associated with improved FFLP and may be the preferable treatment.