Appeal type: Other
Decision: Favorable

We decided that the Plan has to pre-approve proton beam radiation therapy (PBRT) services.
You asked the Plan to pre-approve PBRT. You say that the enrollee could not tolerate surgery and left with few options. You say that definitive proton therapy may offer local control based on published literature. You say that the benefits of a reduced secondary cancer risk, reduced probability of cardiac toxicity, and reduced lung toxicity demonstrate significant benefits from proton irradiation. The Plan denied your request. The Plan says that current medical literature indicates that the standard of care for radiation therapy for breast cancer is standard radiation therapy including Intensity modulated radiation therapy (IMRT). The Plan says that the requested PBRT is not medically necessary.
The Plan must follow Medicare rules. Medicare rules say that if there are no specific coverage rules for an item or service, then that item or service will be covered when it is medically necessary. 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 PBRT. Our reviewer says that PBRT is considered medically reasonable and necessary in this case. 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 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, 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 IMRT, Tomotherapy, prone breast radiation (although not feasible in the post-mastectomy setting), 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 often yield a better dose distribution. This patient reportedly has N2 disease though the treatment fields are not described. This patient had not been able to tolerate surgery, so presumably the plan is to treat the primary site and nodes. 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. 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. MSKCC 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." The most recent version of the NCCN guidelines (v3.2021) 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). An ASTRO model policy for proton therapy does not explicitly address proton therapy for breast cancer. The 2017 model policy includes breast cancer in its Group 2 (sites that are suitable for "Coverage with Evidence Development") category.
This policy includes generic indications for coverage including: "(1) The target volume is in close proximity to one or more critical structures and a steep dose gradient outside the target must be achieved to avoid exceeding the tolerance dose to the critical structure(s). (2) A decrease in the amount of dose inhomogeneity in a large treatment volume is required to avoid excessive dose "hot spot" within the treated volume to lessen the risk of excessive early or late normal tissue toxicity. (3) A photon-based technique would increase the probability of clinically meaningful normal tissue toxicity by exceeding an integral dose-based metric associated with toxicity. (4) The same or immediately adjacent area has been previously irradiated, and the dose distribution within the patient must be sculpted to avoid exceeding the cumulative tolerance dose of nearby normal tissue." Our physician reviewer found that proton therapy is not investigational, but rather whether or not it is superior to non-proton based IMRT, for routine use, is an investigational question. However, despite the uncertainty of any benefit of proton therapy for use in the general population, there is some understanding about acceptable heart exposure relative to risk of cardiac toxicity. The QUANTEC authors describe cardiac tolerances for patients with breast or lymphoma. They comment (for breast) "For partial irradiation, conservative (NTCP) model-based estimates predict that a V25Gy less than 10% (in 2 Gy per fraction) will be associated with a less than 1% probability of cardiac mortality more than 15 years after RT." From the cooperative group RTOG 1005 (NRG) protocol, for radiation to the intact breast, randomizing patients to receive standard versus concurrent boost whole breast radiation: the heart V20, V10 and mean dose should be less than 5%, 30% and 4 Gy respectively with acceptable variations of V25 of 5%, V10 of 35% and mean dose of 5 Gy respectively. The ipsilateral lung V20 requirement is less than 15% (with 20% acceptable); also, V10 less than 35% (40% acceptable) and V5 less than 50% (55% acceptable). The provided DVHs are not legible, though the mean heart dose is markedly reduced with the proton plan from more than 9 Gy to less than 1 Gy. 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 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. Nevertheless, the reduction in mean heart dose with proton therapy in this patient is significant, largely due to the intent to escalate the dose. 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. As no actual planning records are provided other than difficult to read DVHs an isodose lines, it is difficult to know what the proton plan is being compared to. Notably, with VMAT planning (a type of IMRT), the beam rotates around a 360-degree arc, which often unnecessarily increases the low to moderate dose exposure of the heart and lung. A well-designed IMRT plan (in which the beam angles are optimized) or VMAT plan in which the beam entry is restricted to more tangential entry points often achieves sufficient target coverage while properly minimizing dose to the heart and lungs. This complicates a review like this. However, the patient's volumes are likely complex, the prescribed dose is high, and the dosimetric advantage with proton therapy is substantial for this patient. Our physician reviewer found that proton therapy would be considered the accepted standard of medical practice for the enrollee's condition and circumstances.
We looked at this physician's review, the file, and Medicare rules. Based on this information, we decided that Medicare rules for coverage of PBRT have been met. Therefore, we decided that the Plan has to pre-approve proton beam radiation therapy (PBRT) services.
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.