Tumor-Infiltrating Lymphocytes in Low-Risk Patients With Breast Cancer Treated With Single-Dose Preoperative Partial Breast Irradiation

Abstract

Preoperative partial breast irradiation (PBI) has the potential to induce tumor regression. We evaluated the differences in the numbers of preirradiation tumor infiltrating lymphocytes (TILs) between responders and nonresponders after preoperative PBI in low-risk patients with breast cancer. Furthermore, we evaluated the change in number of TILs before and after irradiation. Methods and Materials: In the prospective ABLATIVE study, low-risk patients with breast cancer underwent treatment with single-dose preoperative PBI (20 Gy) to the tumor and breast-conserving surgery after 6 or 8 months. In the preirradiation diagnostic biopsy and postirradiation resection specimen, numbers of TILs in 3 square regions of 450 Â 450 mm were counted manually. TILs were visualized with CD3, CD4, and CD8 immunohistochemistry. Differences in numbers of preirradiation TILs between responders and nonresponders were tested using Mann-Whitney U test. Responders were defined as pathologic complete or near-complete response, and nonresponders were defined "as all other response." Changes in numbers of TILs after preoperative PBI was evaluated with the Wilcoxon signed rank test. Results: Preirradiation tissue was available from 28 patients, postirradiation tissue from 29 patients, resulting in 22 pairs of preirradiation and postirradiation tissue. In these 35 patients, 15 had pathologic complete response (43%), 11 had a nearcomplete response (31%), 7 had a partial response (20%), and 2 had stable disease (6%). The median numbers of CD3 þ TILs, CD4 þ TILs, and CD8 þ TILs in the preirradiation tumor tissue were 49 (interquartile range [IQR], 36-80), 45 (IQR, and 19 (IQR,, respectively. The number of preirradiation TILs did not differ significantly between responders and

Preoperative robotic radiosurgery for early breast cancer: Results of the phase II ROCK trial (NCT03520894)

“…The differences in the numbers of pre-irradiation tumour infiltrating lymphocytes (TILs) between responders and non-responders after preoperative PBI in low-risk patients with breast cancer was also evaluated (22 pairs of pre-irradiation and post-irradiation tissue available). After preoperative PBI in this limited cohort, the number of TILs in tumour tissue decreased, although no differences in numbers of pre-irradiation TILs between responders and non-responders were observed [20] .…”

“…High dose gradient techniques, such as stereotactic body radiation therapy (SBRT), have been routinely implemented in clinical practice thanks to their widespread availability, and are currently used as a curative treatment in several diseases (i.e., non-small cell lung cancer, prostate cancer) [14] , [15] . Several studies assessed the feasibility of PBI using multiple techniques in the preoperative setting followed by standard BCS [16] , [17] , [18] , [19] , [20] . Cyberknife® (Accuray Incorporated, Sunnyvale, CA, USA) is a frameless robotic stereotactic radiosurgery system, providing continuous motion tracking during respiratory movement.…”

Accelerated Partial Breast Irradiation

“…A 5-fraction schedule is the standard regimen and probably the appropriate compromise in terms of efficacy, safety, and HRQoL,10 also considering the negative results of most intraoperative single-fraction PBI trials 11–16. A new frontier is now open on the potential benefit of preoperative PBI delivery,17 although concerns remain on the optimal dose, fractionation, and technique 18–23. Therefore, postoperative PBI still represents the gold-standard of treatment.…”

“…[11][12][13][14][15][16] A new frontier is now open on the potential benefit of preoperative PBI delivery, 17 although concerns remain on the optimal dose, fractionation, and technique. [18][19][20][21][22][23] Therefore, postoperative PBI still represents the gold-standard of treatment. One of the most exciting perspectives is based on trials evaluating the optimization of all adjuvant treatments for lowrisk breast cancer, including but not limited to RT.…”

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial - a study protocol

“…In the ABLATIVE trial, 67% of patients with rCR had a pCR and 33% had near pCR after 6 to 8 months (22). Additionally, the prediction of pCR after pre-operative systemic therapy using liquid biopsies and biomarkers in tumor tissue, such as tumor-in ltrating lymphocytes (TILs), have been evaluated, and to a much lesser extent after pre-operative RT (22,(30)(31)(32). The ABLATIVE trial showed presence of TILs preirradiation and 6 to 8 months post-irradiation (30).…”