Head-to-Head Comparison of [18F]PSMA-1007 and [18F]FDG PET/CT in Patients with Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) exhibits high aggressiveness and a notably poorer prognosis at advanced stages. Nuclear medicine offers new possibilities, not only for diagnosis but also potentially promising therapeutic strategies. This prospective study explores the potential of prostate-specific membrane antigen (PSMA) as a diagnostic and therapeutic target in TNBC. METHODS: the research investigates PSMA expression in vivo among TNBC patients using [18F]PSMA-1007 PET/CT and compares it head-to-head with the standard-of-care [18F]FDG PET/CT. RESULTS: The study involves 10 TNBC patients, revealing comparable uptake of [18F]PSMA-1007 and [18F]FDG in primary and metastatic lesions. Nodal metastases were found in eight patients, showing similar SUVmax values in both modalities. Two patients had uncountable lung metastases positive in both [18F]FDG and [18F]PSMA-1007 scans. PET-positive bone metastases were identified by 18F-PSMA in four patients, while elevated [18F]FDG uptake was found only in three of them. Distant metastases displayed higher SUVmax values in the [18F]PSMA-1007 PET/CT, as compared to [18F]FDG. Additionally, brain metastases were exclusively detected using [18F]PSMA-1007. CONCLUSIONS: the findings provide valuable insights into the expression of PSMA in TNBC and underscore the potential clinical significance of [18F]PSMA-1007 PET/CT in enhancing both diagnostic and therapeutic approaches for this aggressive breast cancer subtype.

Impact of copy number variant and single nucleotide polymorphism of the programmed death-ligand 1 gene, programmed death-ligand 1 protein expression and therapy regimens on overall survival in a large group of Caucasian patients with non-small cell lung carcinoma.

Anti-programmed death-1 or anti-programmed death-ligand 1 (PD-L1) blockade may be ineffective in some patients with non-small cell lung cancer (NSCLC) with high percentage of tumor cells with PD-L1 expression. In addition, immunotherapy may provide great benefits in patients without PD-L1 expression. The present study assessed PD-L1 protein expression by immunohistochemistry, copy number variation (CNV) of PD-L1 and two single nucleotide polymorphisms (SNPs), rs822335 and rs822336, in the promoter of PD-L1 by quantitative PCR in 673 patients with NSCLC. Overall survival time of patients with NSCLC depending on the assessed predictive factors (PD-L1 CNV or SNP) and the treatment methods (immunotherapy in first/second line of treatment or chemotherapy) was analyzed. The present study revealed significantly higher PD-L1 copies number in patients with ≥10% and ≥50% of tumor cells with PD-L1 expression compared to patients with lower percentage of PD-L1-positive tumor cells (P=0.02 and P=0.0002, respectively). There was a significant positive correlation (R=0.2; P=0.01) between number of PD-L1 copies and percentage of tumor cells with PD-L1 protein expression. Percentage of tumor cells with PD-L1 expression was lower in patients with TT genotype of the rs822335 polymorphism compared to those with CC genotype (P=0.03). The present study observed significantly higher risk of death in patients treated with chemotherapy compared to those treated with immunotherapy (P<0.0001; hazard ratio=2.4768; 95% confidence interval, 2.0120-3.0490). The present study demonstrated a close relationship between PD-L1 copies number, genotype of rs822335 PD-L1 polymorphism and PD-L1 protein expression on tumor cells. However, the impact of CNV and SNPs of PD-L1 on overall survival of patients with NSCLC requires further investigation.

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland.

INTRODUCTION: Osimertinib is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated efficacy in the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC) in prospective clinical trials. MATERIAL AND METHODS: This retrospective analysis evaluated the outcomes of 32 pretreated patients with EGFR T790M mutation who received osimertinib in clinical practice at seven centers in Poland within the Expanded Drug Access Program. Osimertinib was used in the second line in 59% of patients and in later lines in 41%. RESULTS: Objective response was attained in 16 patients (50%), and 12 subjects (38%) had stable disease. Median progression -free survival was 11.3 months in the overall population, 12.6 months in patients with EGFR exon 19 mutation and 7.5 months in patients with EGFR exon 21 mutation (p = 0.045). Median overall survival (OS) was 18.3 months. Overall, 58.4% and 45.6% of patients remained in follow-up after 12 and 24 months, respectively. Median OS appeared longer for patients without cerebral metastases than for those with cerebral metastases (27.4 vs 9.4 months, respectively; p = 0.078), and for patients with the Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 than those with ECOG PS 2 (27.4 vs 11.8 months, respectively; p = 0.189), although neither result reached statistical significance. Median OS of patients with partial response, stable disease and progressive disease was 27.4, 12.7 and 4.5 months, respectively (p < 0.001). Age, comorbidities, line of treatment with osimertinib, and type of activating EGFR mutation did not impact on OS. Adverse events of any grade or grade 3/4 were reported in 38% and 9% of patients, respectively. One person discontinued due to interstitial pneumonia. CONCLUSION: These results confirm the value of osimertinib in patients with previously treated EGFR T790M-mutant NSCLC. Clinical benefit was evident in patients with cerebral metastases and moderate performance status.

Tissue MicroRNA Expression as a Predictor of Response to Immunotherapy in NSCLC Patients.

INTRODUCTION: Expression of PD-L1 protein on tumor cells, which is so far the only validated predictive factor for immunotherapy, is regulated by epigenetic and genetic factors. Among the most important ones that regulate gene expression are microRNAs. MATERIALS AND METHODS: The study included 60 patients with NSCLC who underwent first or second line immunotherapy with pembrolizumab or nivolumab. FFPE materials were collected before the start of immunotherapy. We examined relative expression of microRNAs (miR-141, miR-200a, miR-200b, miR-200c, miR-429, miR-508-3p, miR-1184, miR-1255a) and PD-L1 mRNA expression. Copy number variation (CNV) of PD-L1 gene by qPCR and FISH methods were assessed. Two single nucleotide polymorphisms (SNPs) in promoter region of PD-L1 gene (rs822335 and rs822336) were examined. Expression of PD-L1 protein on tumor cells was assessed by immunohistochemistry (IHC). The response rate to immunotherapy and progression free survival (PFS) measured in weeks and overall survival (OS) measured in months from the start of immunotherapy were evaluated. RESULTS: Response to immunotherapy was observed in nine patients (15%, including one complete response), disease stabilization in 22 patients (36.7%), and progression in 29 patients (48.3%). Significantly higher (p=0.015) expression of miR-200b and significantly lower (p=0.043) expression of miR-429 were observed in responders compared to patients who did not respond to immunotherapy. The median PFS in the whole group of patients was 16 weeks, and the median OS was 10.5 month. In univariate analysis, the median PFS was significantly higher in patients with high miR-200b expression (HR=0.4253, 95%CI: 0.1737-1.0417, p=0.05) and high miR-508 expression (HR=0.4401, 95%CI: 0.1903-1.0178, p=0.05) and with low expression of miR-429 (HR=0.1288, 95%CI: 0.01727-0.9606, p=0.0456) compared to patients with low and high expression of these molecules, respectively. The median OS was higher in patients with low expression of miR-429 (HR=0,6288, 95%CI: 0,3053-1,2949, p=0.06) compared with patients with high expression of this microRNA. In multivariate analysis, we found that patients with PD-L1 expression on ≥1% of tumor cells compared to patients without PD-L1 expression on cancer cells had a significantly lower risk of progression (HR=0.3857, 95%CI: 0.1612-0.9226, p=0.0323) and death (HR=0.377, 95%CI: 0.1636-0.8688, p=0.022). CONCLUSION: The miR-200b and miR-429 molecules in tumor cells seem to have greatest impact on the effectiveness of immunotherapy in NSCLC patients.

The comparison of acute toxicity in 2 treatment courses: Three-weekly and weekly cisplatin treatment administered with radiotherapy in patients with head and neck squamous cell carcinoma.

The most appropriate cisplatin treatment schedule delivered with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to compare the acute toxicity and its impact on the course of the treatment, administered cisplatin and radiation doses, the length of hospitalization and supportive drugs administration in patients with HNSCC receiving 2 different cisplatin treatment schedules administered with radiotherapy.In this retrospective analysis, 104 patients with HNSCC were enrolled. Patients received radiation concurrently with 100 mg/m cisplatin administered 3-weekly (n = 50; group A) or 35 to 40 mg/m cisplatin administered weekly (n = 54; group B). Chemoradiotherapy was performed in locally and/or regionally advanced disease (stage III-IV), in a definitive radical upfront setting (71.1%) or after surgical resection in patients with high-risk factors (28.8%).Both study groups were equally distributed in terms of age, gender, stage of the disease, Eastern Cooperative Oncology Group performance score, chronic diseases and primary tumor site. The schedule of cisplatin dosing did not influence the duration of hospitalization, the number of additional supportive drugs (antibiotics, opioids) administered or total doses of received radiotherapy. However, postponement of radiotherapy due to adverse events was significantly more frequent in patients treated with 35/40 mg/m (55.56% vs 32%; P = .015). Furthermore, patients treated with weekly treatment schedule received lower total cisplatin dose (160 mg/m) in comparison to those treated with the 3-weekly schedule (200 mg/m). Grade 3 and 4 mucositis occurred more frequently in patients treated in group A (70% vs 50%; P = .037). Leukopenia was also observed more frequently in group A (88% vs 72.2%; P = .04), however there was no difference in grade 3/4 leukopenia between both study arms. There was no statistically significant difference in any other adverse effects.These results do not demonstrate the advantage of modified weekly schedule over standard 3-weekly cisplatin treatment plan. However, severe mucositis occurred more frequently in patients receiving 3-weekly cisplatin, both chemotherapy schedules seemed to present similar toxicity. Due to conflicting efficacy and toxicity, the results and compliance of weekly and 3-weekly cisplatin schedules should be evaluated in further randomized, controlled trials and retrospective studies.