Proton Radiation for Locally Advanced Breast Cancer: Feasibility and Early Outcomes for 20 Patients on Prospective Clinical Trial
Reporting Author: Abigail T. Berman, MD
Last Modified: June 10, 2013
Presenting Author: Shannon MacDonald, MD Presenting Author Affiliation: Massachusetts General Hospital, Radiation Oncology, Boston
Breast cancer is the leading cancer diagnosis of women in the United States, with 1 in 8 women diagnosed.
The options for treatment include breast conservation surgery (BCS) followed by radiation (RT) or mastectomy. While BCS is an excellent choice for many women, others with locally advanced disease must undergo mastectomy, and many of these will require post-mastectomy radiation (PMRT).
To date, little clinical data exit regarding breast cancer treatment with proton beam therapy.
For locally-advanced breast cancer (LABC), proton therapy after mastectomy can provide improved target coverage, cardiopulmonary sparing and homogeneity. In LABC, the regional nodes often need to be treated with the chest wall. This increased volume increases can increase the dose to the heart and lung. In addition, most LABC patients receive cardiotoxic chemotherapy, and therefore any sparing of heart dose is essential.
Many institutions offer immediate reconstruction, which has both psychologic benefits and avoids multiple surgeries; however this also increases the complexity of RT planning.
Dosimetric planning studies have described potential benefits for the use of proton radiation (RT) for locally advanced breast cancer.
This is a report of the acute toxicities and feasibility of proton delivery for twenty women treated with PMRT with or without reconstruction.
Materials and Methods
Twenty-five women were enrolled on an IRB-approved prospective clinical trial.
Primary endpoints were acute toxicity (skin toxicity and pneumonitis), and secondary endpoints were event-free survival (EFS), long-term cosmesis, and other toxicity.
Eligibility criteria included requirement of PMRT to the chest wall +/- lymph nodes (LN), no metastatic disease, and unfavorable cardiac anatomy. Unfavorable anatomy was defined as estimated volume receiving 20 Gy (V20) >5% and/or requiring manipulation or removal of permanent implant(s). The study did not permit patients treated with BCS or tissue expanders.
All patients underwent CT simulation with contours drawn according to the RTOG guidelines.
The dose to the chest wall was 50.4 cGy (RBE) and lymph nodes 45-50.4 cGy (RBE).
Patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after completion of therapy.
Strain echocardiograms and ultra-sensitive troponin were performed before RT and at 4 and 8 weeks after RT.
All patients consented to have photographs taken for documentation of skin toxicity during and after RT.
25 patients were enrolled from August 2011-January 2013
Twenty-four of 25 patients had left sided breast cancer.
One patient was treated for right-sided breast cancer with bilateral implants.
Median age was 45 years (only 3 patients over age of 50).
From the date of RT start median follow up is 5 months (range, 2-14).
Eleven women had permanent implants at the time of RT and 9 did not have immediate reconstruction.
All patients completed proton RT to a dose of 50.4 Gy (RBE) to the chest wall and 45-50.4 Gy (RBE) to the regional lymphatics delivered with passively scattered protons. One patient received 57.6 Gy (RBE) to the internal mammary nodes (IMN). No photon or electron component was used.
Maximum CTCAE skin toxicity during radiation was grade 2. Maximum CTCAE fatigue was grade 3.
There has been one case of grade 2 RT pneumonitis to date that resolved with a 10-day course of steroids. No cases of lymphedema or rib fracture. There has been one case of implant removal due to contracture.
Median V20 to the heart was 0.18%.
Median V20 to the ipsilateral lung was 12.1% and the mean lung dose was 5.59 Gy.
Proton RT for PMRT is feasible and well tolerated. This treatment may be warranted for select patients with unfavorable cardiac anatomy and/or immediate reconstruction that otherwise limits optimal RT delivery using standard methods.
Longer follow-up is needed.
This is the first report to our knowledge of proton beam therapy for PMRT. The authors describe that it is feasible and safe in patients whose unfavorable cardiac anatomy and/or immediate reconstruction limited the optimal RT delivery using standard methods.
In the final report of this study, it will be helpful to know what dosimetric parameters (mean heart dose, ipsilateral lung V20 and mean dose) were deemed unacceptable for standard radiotherapy.
Dosimetric studies comparing PBT and photon/electron RT to the lymphatic region have already shown that the proton/electron plan is similar to PBT with slightly inferior coverage and less high dose to the lung (MacDonald IJROBP 2009, Fontanilla PRO 2012). Other dosimetric studies have shown heart and lung sparing (Li IJROBP 2009 Feng IJROBP 2011).
This is a feasibility and acute toxicity report; it will be equally important to see the report of long-term cosmesis given that this is a primary outcome in breast cancer.
There is concern in many disease sites that the skin dose may be higher with PBT, particularly double scattering technology, and that, in the case of breast cancer, this could lead to worse cosmesis. In PMRT, the skin is in fact part of the target, so the higher skin dose may be acceptable. In addition, while this study used double scattering, pencil beam scanning (PBS) be better able to modulate entrance dose.
The report did not specifically state if the internal mammary nodes (IMN) were treated (except in one patient where presumably there was a gross node). The elective treatment of IMNs is controversial, supported by the fact that they were included on many of the large PMRT randomized trials (Danish, British Columbia) but refuted by the fact that clinical IMN recurrences occur in <1% of patients, and treatment can increase heart and lung dose (Chen R JCO 2008). The magnitude of dosimetric benefit for proton beam therapy may be greater if treating the IMNs, however this is not necessarily clinically warranted.
Apr 18, 2012 - For patients with nonmetastatic prostate cancer, treatment with intensity-modulated radiation therapy is associated with fewer complications than proton therapy or conformal radiation therapy, according to a study published in the April 18 issue of the Journal of the American Medical Association, a theme issue on comparative effectiveness research.