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Immune checkpoint inhibitors activate T cells to reject tumors. Unique tumor mutations are key Tcell targets, but a comprehensive understanding of the nature of a successful antitumor T-cell response is lacking. To investigate the T-cell receptor (TCR) repertoire associated with treatment success versus failure we used a well-characterized mouse carcinoma that is rejected by CD8 T cells in mice treated with radiotherapy (RT) and anti-CTLA-4 in combination, but not as monotherapy, and comprehensively analyzed tumor-infiltrating lymphocytes (TILs) by highthroughput sequencing of the TCRB CDR3 region. The combined treatment increased TIL density and CD8/CD4 ratio. Assessment of the frequency of T cell clones indicated that anti-CTLA-4 resulted in fewer clones and a more oligoclonal repertoire compared to untreated tumors. In contrast, RT increased the CD8/CD4 ratio and broadened the TCR repertoire, and when used in combination with anti-CTLA-4, these selected T cell clones proliferated. Hierarchical clustering of CDR3 sequences showed a treatment-specific clustering of TCRs that were shared by different

Risk-reduction interventions for BRCA-related breast cancer are relevant not only for clinical decisions in breast cancer patients but also for healthy subjects who are potential candidates to undergo similar interventions. The literature on the impact of different surgical options and adjuvant systemic approaches aimed towards risk reduction for ipsilateral and contralateral breast cancer recurrences is briefly reviewed. Breast-conserving surgery is associated with a higher probability of local recurrence, but is counterbalanced by effectiveness of chemotherapy in reducing this risk. Consistent support for the hypothesis that antiestrogens are effective in reducing contralateral breast cancer risks is available from the literature. On the other hand, data on chemoprevention approaches for healthy subjects are too preliminary to draw any conclusions. Studies including conventional and newer hormonal drugs are needed to demonstrate the benefit of chemoprevention approaches. These may also deepen our knowledge on possible differences in the likelihood of clinical benefit to be expected among BRCA1- and BRCA2-altered tumours.

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Purpose: Challenges for radiation therapy in developing countries include unreliable infrastructure and high patient load. We propose a system to treat whole breast in the prone position without computed tomography and/or planning software. Methods: Six parameters are measured using calipers and levels with the patient prone in the treatment position. (1) The largest separation; (2) the angle that separation makes with the horizontal; (3) the separation 2 cm posterior to the nipple; (4) the vertical distance between these two separations; (5) the sup/inf length and (6) angle of the desired posterior field edge. The data in (5) (6) and (2) provide field length, collimator and gantry angles. Isocenter is set to the midpoint of (1), anterior jaw setting is 20cm (half‐beam setup), and the dose is prescribed to a point 1.5 cm anterior to isocenter. MUs and wedge angles are calculated using an MU calculator and by requiring 100% dose at that point and 100‐105% at the midpoint of (3). Measurements on 30 CT scans were taken to obtain the data 1‐6. To test the resulting MU/wedge combinations, they were entered into Eclipse (Varian) and dose distributions were calculated. The MU/wedge combinations were recorded and tabulated. Results: Performing a dose volume histogram analysis, the contoured breast V95 was 90.5%, and the average V90 was 94.1%. The maximum dose never exceeded 114.5%, (average 108%). The lung V20 was <5% for 96.7%, and the heart V5 was <10% for 93.3% of our sample. Conclusion: A method to provide prone whole breast treatment without CT‐planning was developed. The method provides reasonable coverage and normal tissue sparing. This approach is not recommended if imaging and planning capabilities are available; it was designed to specifically avoid the need for CT planning and should be reserved to clinics that need to avoid that step.