This study addressed an important question of the efficacy of hypofractionated radiotherapy in postmastectomy patients. 820 patients with primary T3-4 disease or at least 4 positive axillary LNs were randomized to receive 50 Gy in 25 fractions over 5 weeks or 43.5 Gy in 15 fractions over 3 weeks. The primary endpoint was 5-year locoregional recurrence, and 5% margin was used to establish non-inferiority design. The median follow-up was 58.5 months. The 5-year cumulative incidence of locoregional recurrence was 8.3% (hypofractionation) vs 8.1% (conventional fractionation), with p < 0.0001 for non-inferiority. Patients receiving hypofractionated radiotherapy had higher chance of grade 3 acute skin toxicity (8%) than those receiving conventional radiotherapy. This study concluded that postmastectomy hypofractionated radiotherapy was non-inferior to conventional fractionated radiotherapy with similar toxicity profile.

Reference (PubMed Link): Wang SL, Fang H, Song YW, et al. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: A randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 2019;20:352-360.

Key Institution: Chinese Academy of Medical Sciences and Peking Union Medical College
Keywords: Postmastectomy radiotherapy, hypofractionation, high-risk breast cancer, locoregional recurrence 

Regional nodal irradiation (RNI) is often recommended for patients following surgery for breast cancer who have risk factors for regional relapse. RNI often includes the internal mammary nodes (IMNs). However, treating the IMNs with radiotherapy increases the dose to the heart and lungs and may increase the long-term risk of toxicity. Proton beam radiation therapy may be able to spare cardiopulmonary radiation exposure although previously there had been no prospective studies showing a benefit.

In the present study, 70 patients completed proton beam radiation including RNI coverage between 2011 and 2016. 91% of these patients had left-sided breast cancers and 94% had stage II or stage III disease. 99% received chemotherapy. On assessment of radiation delivery, the authors found that the median dose to the chest wall/breast was 49.7 Gy and 48.8 Gy to the IMNs. For the 62 surviving patients, the 5-year rates for locoregional relapse and overall survival were 1.5% and 91%, respectively. Only one patient developed grade 2 radiation pneumonitis and no patients developed grade 3 or higher pneumonitis. No grade 4 or higher toxicities occurred. There was no evidence of changes in echocardiograms or cardiac biomarkers.

In conclusion, proton beam radiation therapy for breast cancer including RNI coverage was associated with low toxicity and comparable survival outcomes compared to what would be expected in terms of historical data.

Randomized studies are needed to directly compare protons vs photons, but these are encouraging preliminary findings.

Reference (PubMed Link): Jimenez RB, Hickey S, DePauw N, et al. Phase ii study of proton beam radiation therapy for patients with breast cancer requiring regional nodal irradiation. J Clin Oncol 2019;37:2778-2785.

Key Institution: Massachusetts General Hospital
Keywords: Proton therapy, breast cancer, regional nodal irradiation

The purpose of this study was to determine if 40 Gy in 10 daily fractions is a tolerable dose schema for accelerated partial breast irradiation (APBI) as compared to more traditional twice-daily regimens that have produced mixed cosmetic results in trials. 

There were 106 patients enrolled in the study. Median age was 62 years. All patient received lumpectomy for in-situ or early invasive disease. A 3-D conformal RT technique was used. 

Median follow-up was 58 months. Regarding recurrence outcomes, there were in total 3 recurrences: 2 local, 1 distant. Regarding cosmesis, 15% experienced grade 2 or greater skin toxicity with only two cases of grade 3 skin toxicity. The planning target volume (PTV) and breast volume receiving 20 Gy (V20) were found to be predictors of skin toxicity. The authors suggest that limiting breast V20 to less than 45% may limit skin toxicity, as 62% of patients who developed skin complications had a breast V20 greater than 50%. 

Given these results, 40 Gy in 10 daily fractions may be an appropriate APBI regimen in patients with early stage breast cancer. PTV and V20 may also be accurate predictors of skin toxicity and may be useful constraints in guiding treatment planning. More follow-up will be needed to determine the toxicity profile and safety of this regimen in the long-term. 

Reference (PubMed Link): Braunstein LZ, Thor M, Flynn J, et al. Daily fractionation of external beam accelerated partial breast irradiation to 40 gy is well tolerated and locally effective. Int J Radiat Oncol Biol Phys 2019;104:859-866.

Key Institution: Memorial Sloan Kettering Cancer Center
Keywords: Accelerated Partial Breast Irradiation, APBI, Skin Toxicity, Breast Cancer 

This randomized study was conducted in 537 patients from 22 surgical practices, randomly assigned online to the iCanDecide interactive and tailored Web site (intervention) or the iCanDecide static Web site (control). The aim was to determine the effect of iCanDecide, an interactive and tailored breast cancer treatment decision tool, on the rate of high-quality patient decisions—both informed and values concordant—regarding locoregional breast cancer treatment and on patient appraisal of decision making. The tailored and interactive iCanDecide Web site, which focused on knowledge building and values clarification, positively affected high-quality decisions largely by improving knowledge compared with static online information.

Harnessing available technology to improve oncology outcomes is a largely untapped avenue for clinical research and/or commercial enterprise. Decision making tools such as iCanDecide will become increasingly common in the next decade in a nationwide and global effort to bring quality control to diverse clinical settings. Experiences such as this study will serve to advance this aspect of oncology care. 

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Journal & Date: JCO, 2018
Key Institution: Multicenter
Keywords: Clinical decision making, breast cancer, oncologic surgery, technology, patient decision making, patient centered care