[PAPILLARY THYROID CARCINOMA RESPONDS TO CDK 4/6 INHIBITORS].

INTRODUCTION: Breast cancer and thyroid malignancy are very common tumors in women. These tumors have high curative rates, therefore, a significant probability of both exists during a life-span. Epidemiological studies support the presence of some common risk factors. These data raise questions about biological mechanisms and changes at the molecular level of breast and thyroid cancer cells that may be a target for biological therapy in a common pathway. Here, we present a clinical case of a patient who had metastatic breast cancer and at the time of diagnosis another primary malignant tumor was revealed in the thyroid gland. The issue of treatment choice during two simultaneous active malignancies is always a challenging theme. Surprisingly, both tumors responded to a treatment protocol tailored to a single one. The treatment chosen was not chemotherapy but a special biological treatment combined with hormonal therapy. Further to the case presentation, we discuss molecular changes appearing in both tumors, malignant cell activity mechanisms accordingly, and a basis for biological treatment that may affect two processes simultaneously.

[INTRAOPERATIVE RADIOTHERAPY (IORT) IN EARLY BREAST CANCER - 500 PATIENTS, ONE CENTER'S EXPERIENCE].

AIMS: To present our Institute's experience with intraoperative radiotherapy in this selected population by collecting and analyzing clinical data, including long-term follow-up. BACKGROUND: Breast-conserving therapy is the standard treatment for early-stage breast cancer. The treatment includes tumor resection and a whole breast irradiation. Intraoperative radiotherapy is a single dose of irradiation given to the tumor bed immediately after it is removed. This treatment is suitable for a selected population of patients with early stage breast cancer, which constitutes about 20% of all breast cancer patients and is supposed to replace the standard whole breast radiation treatment. METHODS: Between the years 2006-2017, 737 women with early breast cancer were treated in Carmel Medical Center with intraoperative radiotherapy. We herein report the results of the first 500 patients who were treated until 2015. RESULTS: In 13.8% of the patients, additional breast treatment was recommended due to poor pathological characteristics of the disease in final pathological examination. During a median follow-up period of 74 months (1-136), recurrence was observed in 22 patients (4.4%), and in 7 patients (1.4%) recurrence was observed in regional lymph nodes; 13 patients (2.6%) developed metastatic disease. Risk factors for regional recurrence were identified: tumor size greater than 2 cm, lack of adjuvant therapy and poor genetic profile of the disease. CONCLUSIONS: Intraoperative radiotherapy is feasible and may offer an alternative to the standard whole breast radiotherapy, in low risk early breast cancer patients. The patients should be selected according to known risk factors.

BRAF Mutant Lung Cancer: Programmed Death Ligand 1 Expression, Tumor Mutational Burden, Microsatellite Instability Status, and Response to Immune Check-Point Inhibitors.

INTRODUCTION: The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown. METHODS: Multi-institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (group A, n = 21) and non-V600E (group B, n = 18). Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB) and microsatellite instability status were assessed in 29 (74%), 11 (28%), and 12 (31%) patients, respectively. Objective response rate, progression-free survival (PFS) with ICPi, and overall survival were analyzed. RESULTS: High (≥50%), intermediate (1-49%), and no (<1%) PD-L1 expression was observed in 8 of 19 (42%), 6 of 19 (32%), 5 of 19 (26%), and 5 of 10 (50%), 1 of 10 (10%), and 4 of 10 (40%) cases in groups A and B, respectively. Two tumors in group A showed high TMB (25%); none were microsatellite instability status-high. Twenty-two patients (group A, n = 12; group B, n = 10) received ICPi. Objective response rate with ICPi was 25% and 33% in groups A and B, respectively (p = 1.0). Median PFS with ICPi was 3.7 months (95% confidence interval [CI]: 1.6-6.6), and 4.1 months (95% CI: 0.1-19.6) in groups A and B, respectively (log-rank test = 0.81, p = 0.37). Neither BRAF mutation type nor PD-L1 expression affected the response probability/PFS. Median overall survival was not reached (95% CI: 13-NR) and comprised 21.1 months (95% CI: 1.8-NR) for patients who were and were not exposed to ICPi, respectively (log-rank test = 5.58, p = 0.018). CONCLUSIONS: BRAF mutant NSCLC is associated with high level of PD-L1 expression, low/intermediate TMB and microsatellite-stable status. ICPi have favorable activity both in BRAF V600E and BRAF non-V600E mutant NSCLC.