Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Breast Cancer
Treatment: Proton Beam Therapy, Pre-service
The insurer denied the Proton Beam Therapy, Pre-service.
The denial is overturned.

The patient is a woman with invasive ductal carcinoma of the right breast, cT2mN1. She is s/p (status post) neoadjuvant chemotherapy followed by bilateral mastectomy with immediate reconstruction.

Pathology showed partial response Stage 1 tumor, stage 1a lymph nodes (ypT1cpN1a).

Proton beam therapy is being requested to deliver adjuvant radiation therapy to the right chest wall and regional nodes.

Proton beam therapy is provided on IRB (institutional review board)-approved prospective chart review of patients treated with proton beam therapy, REG001-09, WIRB (Western Institutional Review Board) protocol-20091082.

Yes, the health plan should cover the Proton beam therapy.

The ASTRO (American Society for Radiation Oncology) Proton Beam Therapy Model Policy states that Proton beam therapy is an advanced type of external-beam radiation therapy that uses proton rather than photon beams to deliver radiation doses to a tumor. Proton therapy offers a high degree of precision, which allows radiation oncologists to target an escalated dose of radiation directly on a tumor and spare nearby healthy tissue. Proton therapy is particularly beneficial for patients with tumors that are near critical structures, such as lung tumors near the heart.

Based on new evidence published since the original policy was issued, the updated model policy outlines two categories of appropriate clinical indications, or diagnoses, for proton beam therapy. For indications in Group 1, coverage is recommended; for Group 2, coverage is recommended if additional requirements (outlined below) are met. Disease sites were assigned to one of the two categories based on evidence in published clinical data and current Medicare coverage.

Group 1 indications, or the clinical scenarios that frequently support the use of proton therapy based on medical necessity and published clinical data, were updated with five additions and one modification. Group 1 indications, with additions marked by asterisks, include:

1) Malignant and benign primary central nervous system (CNS) tumors* 2) Advanced (e.g., T4 [Type 4 tumor]) and/or unresectable head and neck cancers* 3) Cancers of the paranasal sinuses and other accessory sinuses* 4) Non-metastatic retroperitoneal sarcomas* 5) Reirradiation cases where cumulative critical structure dose would exceed tolerance dose* 6) Hepatocellular cancer (no longer required to be treated in a hypofractionated regimen*) 7) Ocular tumors, including intraocular melanomas 8) Tumors that approach or are located at the base of skull, including but not limited to chordoma and chondrosarcomas 9) Primary or metastatic tumors of the spine where the spinal cord tolerance may be exceeded with conventional treatment or where the spinal cord has previously been irradiated 10) Primary or benign solid tumors in children treated with curative intent and occasional palliative treatment of childhood tumors when one of the criteria noted above apply 11) Patients with genetic syndromes making total volume of radiation minimization crucial, such as but not limited to NF-1 (neurofibromatosis type 1) patients and retinoblastoma patients.

The policy recommends coverage for Group 2 indications if the patient is enrolled in either an IRB-approved study or in a multi-institutional registry adhering to Medicare requirements for Coverage with Evidence Development (CED). These indications also represent the disease sites for which evidence is accumulating and may support future Group 1 coverage. While the policy specifies that no indications are deemed inappropriate for CED, it also specifies several systems for Group 2 indications:

1) Non-T4 (Type 4 tumor) and resectable head and neck cancers (previously all head and neck malignancies*) 2) Non-metastatic prostate cancer (previously grouped with genitourinary carcinomas*) 3) Breast cancer* 4) Thoracic malignancies, including non-metastatic primary lung and esophageal cancers 5) Abdominal malignancies, including non-metastatic primary pancreatic, biliary and adrenal cancers 6) Pelvic malignancies, including non-metastatic rectal, anal, bladder and cervical cancers

The requested proton beam RT (radiation therapy) is provided on IRB-approved prospective chart review of patients treated with proton beam therapy, REG001-09, WIRB protocol-20091082.

Therefore, the requested proton beam RT is consistent with the ASTRO model policy for proton beam RT, and the health plan should cover the proposed treatment.

Yes, published studies suggest that proton beam radiation offers superior dosimetry to photon radiation treatment dosimetry, and side effects of proton beam therapy offer potentially less local side effects compared to photons in several types of malignancy.

According to Mihailidis DN, "Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT (radiation therapy) delivery using standard methods."

Additionally, from Braunstein LZ & Cahlon O, "With advances in the overall treatment paradigm for breast cancer, most patients with localized disease now exhibit long-term disease control and, consequently, may manifest the late toxicities of aggressive treatment. As a result, there is increasing emphasis on the mitigation of iatrogenic morbidity, with particular attention to heart and lung exposure in those receiving adjuvant radiotherapy. Indeed, recent landmark analyses have demonstrated an increase in significant cardiac events that is linked directly to low-dose radiation to the heart. Coupled with practice-changing trials that have expanded the indications for comprehensive regional nodal irradiation, there exists significant interest in employing novel technologies to mitigate cardiac dose while improving target volume coverage. Proton radiotherapy enjoys distinct physical advantages over photon-based approaches and, in appropriately selected patients, markedly improves both target coverage and normal tissue sparing." 

Finally, Orecchia R, et al states, "Proton therapy is able to optimize the dose to the target and to reduce the irradiation of the healthy tissues. Clinical studies are expected to show a decreased risk of late side effects with potential improvement of the quality of life of breast cancer patients."      

Proton beam therapy is currently the subject of an ongoing clinical trial for this patient's condition: Phase 2 Trial: Proton Radiation for Stage II/III Breast Cancer (ClinicalTrials.gov Identifier: NCT01758445). The purpose of this study is to look at the rates of acute and long-term adverse events of postoperative proton radiotherapy for complex loco-regional irradiation in women with loco-regionally advanced breast cancer.

ASTRO guidelines are the standard guidelines in the radiation oncology community. Despite the therapy being currently the subject of an ongoing clinical trial for the patient's condition, it is consistent with the standard of care when performed in a manner that meets ASTRO Proton Beam Therapy Model Policy, as is being done in this case. Thus, the proton beam therapy should be covered by the health plan in this case.