Appeal type: Practitioner Services
Decision: Favorable

 
We decided that the Plan has to pre-approve Proton Beam Radiation Therapy (PBRT). 
 
You asked the Plan to pre-approve Proton Beam Radiation Therapy (PBRT). You say that the requested PBRT 
is medically necessary. The Plan denied your request. The Plan says that the requested PBRT is not medically 
necessary. 
 
The Plan must follow Medicare rules. Medicare rules say that items and services that are not medically 
necessary are not covered.  
 
We asked our physician reviewer to carefully review the case file and apply the relevant Medicare rules to 
determine if the Plan was correct in denying the request to pre-approve Proton Beam Radiation Therapy 
(PBRT). Our reviewer says that the requested PBRT is medically necessary. Our physician reviewer found a 
proton is the charged nucleus of a hydrogen atom (hydrogen atom minus an electron).  Charged particles (such 
as protons and carbon) can be used to deliver therapeutic radiation. Standard radiation is delivered with a 
linear accelerator (LINAC), which delivers photon therapy (akin to high energy light), while protons (and other 
charged particles) are generated from a cyclotron. The difference between proton and photon irradiation is that 
the protons (or charged particles) stop abruptly in the tissue (Bragg peak) so there is less exit dose through 
normal tissue. 
 
The use of proton therapy is an accepted radiation technology, that has proven efficacy and tolerability. Certain 
conditions- such as base of skull chordomas and chondrosarcomas, and pediatric Central Nervous System 
(CNS) malignancies are probably best treated with proton therapy, due to the sharp dose fall off, allowing high 
dose delivery to the tumor, while relatively sparing the neighboring normal tissue. 
 
While small studies have demonstrated the ability of proton therapy to reduce lung and cardiac (for left sided 
breast cancer) dose exposure (reference 1-3), it is not clear if such reductions are clinically meaningful for 
proton therapy to be recommended for general use. Many other technologies allow for reduction in normal 
tissue dosing, including Intensity-modulated radiation therapy (IMRT), Tomotherapy, prone breast radiation, 
motion management (breath hold, gating, tracking/monitoring).  
 
When treating patients with complex target volumes and/or when needing to treat internal mammary, 
supraclavicular and axillary nodes, proton therapy may yield a better dose distribution that is clinically 
meaningful. 
 
In a dosimetric comparison study of 10 women with Stage III breast cancer who were treated to the breast and 
regional nodes (including internal mammary), proton therapy (vs. 3DRT and IMRT) most reduced the cardiac 
dose exposure (reference 8).  The authors emphasized that the proton therapy plans enabled treatment of the internal mammary nodes and 
provided better cardiac sparing than non-proton plans that did not encompass the internal mammary nodes.  
 
Memorial Sloan Kettering Cancer Center (MSKCC) (reference 9) reported early outcomes in 30 patients 
treated with proton therapy, of whom 93% underwent internal mammary node radiation. Their median mean 
heart dose was 0.88 Gy and median ipsilateral lung V20 was 16.5%. They conclude: Further follow-up is 
necessary to assess for clinical outcomes and cardiopulmonary toxicities 
 
Unlike the patients in those studies, this patient is not undergoing nodal radiation other than encompassing the 
low axilla (which would be included in high tangent fields). 
 
The most recent versions of the National Comprehensive Cancer Network (NCCN) guidelines do not address 
proton therapy for breast cancer (as they do for some other sites such as lung cancer, head and neck cancer and 
prostate cancer).   
 
Thus, I do not think that proton therapy is investigational, but rather whether or not it is superior to non-proton 
based IMRT, for routine use, is an investigational question. 
 
One study showed a ~7.4% increase in risk per Gy of mean heart dose (Darby et al. NEJM 2013: 987-98).  
Other studies have shown similar findings (Taylor et al. JCO 2017: 1641-9 and Jacobse et al. IJROBP 2019: 
595-604). How these findings translate into mean cardiac dose exposure with more modern radiation planning 
remains unknown and is an area of active investigation. More modern studies have examined dose to the 
coronary arteries which may be more relevant than mean cardiac dose or overall heart dose-volume exposure. 
This is being studied in the aforementioned Radiotherapy Comparative Effectiveness (RADCOMP) study, 
planned to accrue 1,716 patients. Using mean dose with modern treatment planning may not be meaningful as 
risks from modern treatment planning tend to be low (reference 12). 
 
A study (cited in the appeal  Zureick et al  reference 14) suggested that dose to the left anterior descending 
(LAD) artery correlated with cardiac events with the authors identified a threshold LAD Dmean EQD2 of 2.8 
Gy (area under the ROC curve, 0.69), above which the risk for any cardiac event was higher (P = .001). Similar 
results were seen when stratifying by LAD Dmax EQD2 of 6.7 Gy (P = .005) and heart Dmean EQD2 of 0.8 
Gy (P = .01). 
 
Another study (reference 10) has shown that even when accounting for motion using deep inspiration breath 
hold, proton therapy can reduce dose to the left anterior descending artery for left-sided breast cancer. 
Nevertheless, a dosimetric comparison is generally needed to justify proton therapy for situations for which 
routine use is not standard.   
 
Despite the uncertainty of any benefit of proton therapy for use in the general population, there is some 
understanding about acceptable lung and heart exposure relative to risk of toxicity. Either the QUANTEC 
reports or the cooperative group studies such as NRG 1005 can provide guidance for acceptable normal tissue 
exposure.  
 
In the NCCN guidelines for prostate cancer, they note that These studies suffer from the biases and talents of 
the investigators ... [and] dosimetric studies ... can suggest that the right treatment planning can make an 
IMRT plan beat a proton therapy plan and vice versa, they do not predict accurately clinically meaningful 
endpoints.  This applies to breast cancer as well which complicates reviews like this.   
 
For this enrollee, the records describe a comparison plan with proton therapy vs. Volumetric modulated arc 
therapy (VMAT) (not specified if with using deep inspiration breath hold or why an IMRT with optimal 
selection of beam angles was not attempted).  Screen captures show isodose lines. Dose-volume histograms are 
also included as is a summary table.   
The lung and heart dosimetry for both plans meet the NRG 1005, QUANTEC and RADCOMP constraints. So, 
the heart and lung dose exposures with the non-proton-based plan do not meet the RTOG 1005 constraints, 
though do meet the RADCOMP exposures. It is not immediately clear why the non-proton-based plan 
exposures are so high though I suspect that a non-optimized VMAT plan was designed for comparison. I would 
expect that the heart and lung exposures could be reduced with a deep inspiration breath hold and a better 
designed VMAT plan, or an IMRT plan in which tangential beam angles were selected as opposed to VMAT in 
which the beams enter and exit around an arc that will unnecessarily increase heart and lung exposures simply 
because the beam enters and exits in such a manner to do so.  
 
The appeal letter describes complex anatomy but does not really specify as to what this means; nothing in the 
consultation note describes this either. The letter describes a cavity close to the chest wall over the heart, which 
is not a highly unusual situation. No actual planning records are provided, just a summary table. There is also a 
meaningless screen capture of a case control that I would assume a physician did not write or review since it 
points to unnecessary radiation to the heart on a computed tomography (CT) slice that does not show the heart. 
The letter also cites new ASTRO guidelines that are outdated. So, this case is very challenging in that the 
appeal letter is a template/boilerplate letter with the only meaningful information being the plan comparison 
table, with no actual planning records.  
 
Nevertheless, if her tumor cavity is above the heart, it is possible that proton therapy would result in clinically 
meaningful benefits. The reduction in heart and lung exposures with proton therapy seem clinically 
meaningful, and the potential benefit is plausible.  
 
In a review like this it is not possible to ascertain if a better VMAT/IMRT plan would be appropriate. As the 
comparison plan data are inappropriate for VMAT/IMRT (by NRG, albeit not RADCOMP criteria) the need 
for proton therapy can be asserted. 
 
We looked at this physician's review, the file, and Medicare rules. Based on this information, we decided that 
Medicare rules for coverage of Proton Beam Radiation Therapy (PBRT) have been met. Therefore, we decided 
that the Plan has to pre-approve Proton Beam Radiation Therapy (PBRT).  
 
If the Plan does not agree with our decision, they can ask us to open a case again. We only open a case again 
if we believe there was a mistake or if there is new information to review. The Plan has to show us the mistake 
and/or send us the new information. This does not happen often. If we decide to open the case again, we will 
send you a letter.