Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis:  Recurrent and metastatic endometrial cancer.
Treatment:  Proton treatment delivery; intermediate and Proton treatment delivery; complex.
The insurer denied proton treatment delivery; intermediate and proton treatment delivery; complex.  The denial is overturned.

Yes, the health plan should cover the requested proton beam radiation therapy and is likely to be more beneficial.

The patient is a female with a history of endometrial carcinoma, s/p (status post) TLH-BSO (total laparoscopic hysterectomy- bilateral salpingo-oophorectomy) and pelvic noodle dissection followed by adjuvant vaginal brachytherapy.  She subsequently presented with metastatic recurrence in the cervical, retroperitoneal, pelvic nodes and omentum s/p systemic therapy.  The patient has progressive symptoms from her disease.  Additional radiation treatment was recommended, and proton beam radiation therapy was requested.

Proton beam radiation therapy is a type of very precise external radiation treatment in which protons are used to treat cancer and other conditions.  Compared to photon, a proton beam that is delivered with sufficient energy has a low "entrance dose."  A proton beam also has a high-dose "Bragg peak" region, which is designed to cover the entire tumor, and there is no "exit dose" beyond the tumor involved in proton radiation therapy.  Because of this unique property, proton beam therapy is highly successful in minimizing damage to normal tissue and surrounding organs, resulting in fewer side effects.  It is an FDA-approved procedure, and it is not subject to IRB (institutional review board) review.

Recurrent endometrial cancer that requires repeat radiation to the abdomen and pelvis is rare, and clinical data in the literature is limited.  However, there are studies that show that proton therapy is superior in sparing the surrounding tissue as compared to photon-based techniques.  A 2012 study compared 3D, IMRT (intensity modulated radiation therapy) and proton therapy techniques for retroperitoneal sarcomas.  The bowel and kidney dose was significantly reduced with proton therapy compared to photon therapy, and the authors concluded that "Based on Quantitative Analysis of Normal Tissue Effects in Clinic benchmarks, the dosimetric advantage of proton therapy may be less gastrointestinal and genitourinary toxicity."  

Another 2017 study evaluated patient with recurrent pancreatic cancer following definitive radiation that received reirradiation using proton therapy.  There was a rate of 13% acute greater than or equal to grade 3 toxicities attributed to proton therapy.  The median overall survival (OS) was 16.7 months and OS at 1 year was 67%.  The authors concluded that "PRT was well tolerated, resulted in prolonged clinical outcomes compared to historical controls, and should be considered as a treatment option with concurrent chemotherapy in selected patients with locally-recurrent pancreatic cancer." 
 
In order to provide a better chance of local control and symptomatic relief, additional radiation therapy was necessary.  In this case, the patient already had a prior course of radiation therapy, and additional radiation to the same area may cause excessive pelvic toxicity.  In addition, the patient has a horseshoe kidney, which is in close proximity to the treatment target of the paraaortic nodes.  A proton therapy/IMRT comparison plan was done.  The mean horseshoe kidney dose was 18.6Gy with IMRT (which exceeded tolerance), and 13.7Gy with proton therapy (within tolerance).  Proton beam radiation therapy would be able to spare the horseshoe kidney, while the photon plan would have a high risk of causing kidney damage.  The requested proton therapy, therefore, is medically appropriate.