High Marks for Proton-Beam RT in Breast Cancer

In Clinical Studies News by Barbara Jacoby

By: Charles Bankhead

From: medpagetoday.com

Women with locally advanced breast cancer requiring regional lymph node irradiation had similar disease control with less toxicity with proton-beam radiation therapy (RT) as compared with historical patients treated with conventional radiotherapy, investigators in a small prospective study reported.

The 69 evaluable patients had a 5-year locoregional failure rate of 1.5% and 5-year overall survival (OS) rate of 91%. No patient developed grade 3 pneumonitis (the primary endpoint) or any grade 4 toxicity, and no significant changes in cardiac function or cardiac biomarkers occurred after radiotherapy, according to Shannon M. MacDonald, MD, of Massachusetts General Hospital in Boston, and colleagues.

A third of the patients at risk of breast implant loss had unplanned repeat surgical intervention, they reported in the Journal of Clinical Oncology.

“In our prospective trial of women with locally advanced breast cancer who required treatment of the internal mammary nodes (IMNs), proton beam RT was safe and effective,” the authors concluded. “Future research will provide needed information about the potential long-term normal tissue-sparing benefits of this complex treatment modality compared with conventional radiation.”

The trial, the first of its kind, provided preliminary data from the ongoing phase III RadCOMP Consortium Trial comparing conventional photon RT and proton-beam RT in women with locally advanced breast cancer, the authors noted.

The preliminary data may bode well for the ongoing phase III trial, according to Benjamin Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“The findings from this trial support the ongoing prospective randomized trial,” said Smith, a clinical expert for the American Society for Radiation Oncology (ASTRO). “The outstanding local control and toxicity profile of proton therapy in this study support the notion that proton therapy is indeed both effective and safe for this indication and that continued enrollment to the RadCOMP trial is warranted.”

In women with high-risk early breast cancer or locally advanced disease, regional nodal irradiation decreases the risk of locoregional recurrence and improves disease-free survival (DFS). Two recent clinical trials, one originating in Canada and the other in Europe, demonstrated improved DFS with nodal irradiation versus whole-breast or chest-wall irradiation alone. In both trials, the treatment protocol included the IMNs, MacDonald and colleagues noted.

Clinical guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network suggest inclusion of the IMNs for at least some patients requiring regional nodal irradiation. However, IMN exposure to RT increases cardiopulmonary exposure as well, which has been associated with an increased risk of cardiac events, the authors continued.

Proton-beam RT might significantly reduce cardiopulmonary exposure. Multiple dosimetric-planning studies demonstrated superior targeting and delivery of radiotherapy with proton versus photon RT, reducing exposure to the heart and lungs. Because of these potential advantages, proton-beam RT is under investigation in breast cancer, although the RadCOMP trial is the first randomized comparison of proton and photon RT.

From 2011 to 2016, MacDonald and colleagues enrolled 70 patients for a prospective evaluation of proton-beam RT in patients with locally advanced breast cancer requiring regional lymph node irradiation. The patients were considered suboptimal candidates for conventional RT because of inadequate target coverage or increased radiation exposure to the heart or left anterior descending coronary artery (LAD).

The study’s primary endpoint focused on the short-term safety of proton-beam RT: incidence of grade ≥3 pneumonitis or any grade 4 toxicity within 3 months of RT. Secondary endpoints included 5-year incidence of locoregional failure and OS.

The radiotherapy protocol included a dose unit gray equivalent of 50.4 Gy in 28 fractions for the chest wall for patients who underwent mastectomy. For patients who had lumpectomy, the dose unit gray equivalent was 45.0 Gy in 1.8-Gy fractions, followed by a 14.4-Gy boost to the lumpectomy cavity. The prescribed dose to the IMN ranged between 45 and 50.4 Gy in fractions of 1.8 to 2.0 Gy. Additionally, maximum exposure limits were specified for the esophagus, heart, LAD, and ipsilateral lung.

The evaluable patients had a median age of 45, and the 62 surviving patients had a median follow-up of 55 months. All but six of the patients had left-sided breast cancer; five had right-sided breast cancer, and two had bilateral disease. All but four patients had stage II-III disease, all but one received chemotherapy, and 50 had immediate breast reconstruction.

Analysis of the primary endpoint showed a 0% incidence of grade ≥3 radiation pneumonitis and no grade 4/5 toxicity. Grade 3 toxicity consisted of acute dermatitis in two patients, and one case each of subacute/late seroma and infection. The most common grade 2 treatment-related toxicity was acute dermatitis (57, 83%) and acute fatigue (24, 35%). The most common subacute/late toxicities were grade 1 hyperpigmentation (36, 52%) and grade 1 telangiectasia (11, 16%).

In addition to the 5-year locoregional failure rate of 1.5% and OS rate of 91%, the distant metastasis-free survival rate was 86%.

A total of 53 patients had attempted reconstruction, 39 before RT and 14 afterward. The authors reported that 15 of the 53 had RT-related complications, and two had reconstructive loss associated with RT. In a subgroup of 48 patients at risk for pre-RT implant loss, the 5-year actuarial rate of unplanned surgical re-intervention was 33%.