Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases.

PURPOSE: Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). METHODS AND MATERIALS: We prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. RESULTS: Patients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. CONCLUSIONS: These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.

Molecular and Kinetic Analyses of Circulating Tumor Cells as Predictive Markers of Treatment Response in Locally Advanced Rectal Cancer Patients.

Neoadjuvant chemoradiation (NCRT) followed by total mesorectal excision is the standard treatment for locally advanced rectal cancer (LARC). To justify a non-surgical approach, identification of pathologic complete response (pCR) is required. Analysis of circulating tumor cells (CTCs) can be used to evaluate pCR. We hypothesize that monitoring of thymidylate synthase (TYMS) and excision repair protein, RAD23 homolog B (RAD23B), can be used to predict resistance to chemotherapy/radiotherapy. Therefore, the aims of this study were to analyze CTCs from patients with LARC who underwent NCRT plus surgery for expression of TYMS/RAD23B and to evaluate their predictive value. Blood samples from 30 patients were collected prior to NCRT (S1) and prior to surgery (S2). CTCs were isolated and quantified by ISET®, proteins were analyzed by immunocytochemistry, and TYMS mRNA was detected by chromogenic in situ hybridization. CTC counts decreased between S1 and S2 in patients exhibiting pCR (p = 0.02) or partial response (p = 0.01). Regarding protein expression, TYMS was absent in 100% of CTCs from patients with pCR (p = 0.001) yet was expressed in 83% of non-responders at S2 (p < 0.001). Meanwhile, RAD23B was expressed in CTCs from 75% of non-responders at S1 (p = 0.01) and in 100% of non-responders at S2 (p = 0.001). Surprisingly, 100% of non-responders expressed TYMS mRNA at both timepoints (p = 0.001). In addition, TYMS/RAD23B was not detected in the CTCs of patients exhibiting pCR (p = 0.001). We found 83.3% of sensitivity for TYMS mRNA at S1 (p = 0.001) and 100% for TYMS (p = 0.064) and RAD23B (p = 0.01) protein expression at S2. Thus, TYMS mRNA and/or TYMS/RAD23B expression in CTCs, as well as CTC kinetics, have the potential to predict non-response to NCRT and avoid unnecessary radical surgery for LARC patients with pCR.

Tumor control, eye preservation, and visual outcomes of ruthenium plaque brachytherapy for choroidal melanoma.

PURPOSE: To evaluate outcomes in patients with posterior choroidal melanoma treated with ruthenium ((106)Ru) brachytherapy. METHODS AND MATERIALS: A retrospective single institutional analysis of 83 of 94 consecutive patients who underwent (106)Ru brachytherapy was performed. Disease was mainly staged as small- and medium-sized nonmetastatic melanoma. The main parameters evaluated were tumor control (local control [LC] and progression-free survival [PFS]) and ocular preservation (enucleation-free survival [EFS]). Besides, functional evaluation was performed and complications were described. RESULTS: The median follow-up was 39 (6-83) months. The median values of height and maximal basal diameter were 4.3 and 9.3mm, respectively. Median apical and basal doses were 100 and 307Gy, respectively. The actuarial 2-year LC, PFS, and EFS were 96.2%, 96.2%, and 95.5%, respectively. Actuarial 5-year LC, PFS, and EFS were 93.6%, 93.6%, and 84.1%, respectively. Preinsertion visual acuity (VA) maintenance was 34% (equal or better than before treatment). Approximately 56% of patients stayed with a minimum functional VA of 0.1 or more, from whom more than half stayed with 0.5 or more. Cataract was seen in 16% of treated eyes, and glaucoma was the rarest complication, with an incidence of 3%. CONCLUSIONS: Small- and medium-sized choroidal melanomas can be adequately treated with (106)Ru brachytherapy, with high rates of tumor control and ocular preservation. Moreover, acceptable incidence of complications such as glaucoma and cataract are seen, and a reasonable part of patients stay with a minimum functional VA.