Background Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or HER2 status during the evolutionary course of metastatic breast cancer and the effect of tumor classification subtype switching remain understudied and underappreciated in brain metastasis patients. Methods Using PRISMA guidelines, a systematic review of series published prior to April 2020 obtained from the Medline database of biopsied or resected breast cancer brain metastasis (BCBM) was performed. Weighted random effects models were used to calculate pooled estimates. Results 15 full-text articles were included with receptor expression analyses on 1373 patients who underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. Primary tumor receptor expression immunophenotypes were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding BCBM immunophenotypes were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. On primary/BCBM comparison, 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordant on ER, 23.0% (95% CI: 18.0%-30.0%) discordant on PR, and 12.0% (95% CI: 8.0%-16.0%) discordant on HER2 status. The most common receptor conversions found in BCBM were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%). Conclusions BCBM exhibit significant receptor expression discordance in comparison to primary tumors in approximately 40% of patients. Classification patterns need to be analyzed to determine factors predictive of BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.
Purpose: The objectives of this study were to evaluate the implementation, device usage rates, clinical outcomes, and treatment-related toxicities associated with TTFields and pemetrexed plus platinum-based chemotherapy in patients with unresectable MPM, outside the initial trial results. Methods: Consecutive patients with unresectable MPM were enrolled onto an FDA-required HDE protocol from 2019 to 2021. All patients were treated with a protocol-defined regimen of continuous TTFields (150 kHz) and pemetrexed plus platinum-based chemotherapy. Results: Five patients with unresectable MPM were enrolled. The median number of 4-week TTFields cycles was 5 (range: 2–7 cycles). Median TTFields device usage in the first 3 months was 12.5 h per day (range: 5–16.8 h), representing 52% (21–70%) of the potential daily duration. The median follow-up was 5.4 months (range: 1.1–20.9 months). Treatment-related dermatitis was the only side effect associated with TTFields and was reported as grade 1–2 in all patients; no patient had grade 3+ device-related toxicities. Conclusions: This study represents the first results of real-world implementation of TTFields for MPM. In comparison to the initial clinical trial (STELLAR), compliance rates were lower, although skin-related toxicities appeared similar. Further initiatives and guidelines should be developed to manage treatment-related dermatitis and improve device usage.
Background Novel immunotherapeutic strategies targeting the PD-1/PD-L1 axis are often administered when metastatic tumors show PD-L1 positivity, even in the setting of lung cancer brain metastasis (LCBM). However, biological differences exist between primary tumors and metastatic sites. The objective of this study was to analyze rates of PD-L1 receptor discordance between primary tumors and LCBM. Methods A systematic review of studies of biopsied or resected LCBM evaluating PD-L1 discordance published in the Medline database was performed using PRISMA guidelines. Weighted random effects models were used to calculate pooled estimates. Results Six full-text articles (n=230 patients) with a median of 32 patients in each study (range: 24-73) reported PD-L1 receptor expression analyses of both primary lung tumors and brain metastases and met inclusion criteria. The pooled estimate for tumor cell (TC) PD-L1 receptor discordance between primary tumors and LCBM was 19% (95% CI: 10%-27%). For PD-L1 receptor expression in tumor infiltrating lymphocytes (TIL), the weighted pooled estimate for discordance was 21% (95% CI: 8%-44%). For primary versus LCBM, the positive rates by expression levels of <1%, 1-50%, and >50% were 52% (95% CI: 30-73%) vs. 56% (95% CI: 34-76%), 30% (95% CI: 22-40%) vs. 20% (95% CI: 10-35%), and 15% (95% CI: 6-36%) vs. 22% (95% CI: 15-31%) (p=0.425), respectively. Conclusions PD-L1 discordance occurs in ~20% of LCBM, with the greatest discordance in the 1-50% expression category. Although controversial, confirming discordance might be important for selection of immune checkpoint inhibitor therapy and in the analysis of patterns of failure after treatment.
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