The Impact of the COVID-19 Pandemic on the Number of Cancer Patients and Radiotherapy Procedures in the Warmia and Masuria Voivodeship.

(1) Background: It was suspected that the COVID-19 pandemic would negatively affect health care, including cancer treatment. The aim of the study was to assess the impact of the COVID-19 pandemic on the number of radiotherapy procedures and patients treated with radical and palliative radiotherapy in Poland. (2) Methods: The study was carried out in Warmia and Masuria voivodeship. The number of procedures and treated patients one year before and in the first year of the COVID-19 pandemic were compared. (3) Results: In the first year of the COVID-19 pandemic, the number of radiotherapy procedures and cancer patients treated with radiotherapy in Warmia and Masuria voivodeship in Poland was stable compared to the period before the pandemic. The COVID-19 pandemic has not affected the ratio of palliative to radical procedures. The percentage of ambulatory and hostel procedures significantly increased with the reduction of inpatient care in the first year of the COVID-19 pandemic. (4) Conclusion: No significant decrease in patients treated with radiotherapy during the first year of the pandemic in Warmia and Masuria voivodeship in Poland could indicate the rapid adaptation of radiotherapy centers to the pandemic situation. Future studies should be carried out to monitor the situation because the adverse effects of the pandemic may be delayed.

Correlation between quantitative HER-2 protein expression and risk for brain metastases in HER-2+ advanced breast cancer patients receiving trastuzumab-containing therapy.

BACKGROUND: Patients with human epidermal growth factor receptor (HER)-2+ breast cancer are at particularly high risk for brain metastases; however, the biological basis is not fully understood. Using a novel HER-2 assay, we investigated the correlation between quantitative HER-2 expression in primary breast cancers and the time to brain metastasis (TTBM) in HER-2+ advanced breast cancer patients treated with trastuzumab. METHODS: The study group included 142 consecutive patients who were administered trastuzumab-based therapy for HER-2+ metastatic breast cancer. HER-2/neu gene copy number was quantified as the HER-2/centromeric probe for chromosome 17 (CEP17) ratio by central laboratory fluorescence in situ hybridization (FISH). HER-2 protein was quantified as total HER-2 protein expression (H2T) by the HERmark® assay (Monogram Biosciences, Inc., South San Francisco, CA) in formalin-fixed, paraffin-embedded tumor samples. HER-2 variables were correlated with clinical features and TTBM was measured from the initiation of trastuzumab-containing therapy. RESULTS: A higher H2T level (continuous variable) was correlated with shorter TTBM, whereas HER-2 amplification by FISH and a continuous HER-2/CEP17 ratio were not predictive (p = .013, .28, and .25, respectively). In the subset of patients that was centrally determined by FISH to be HER-2+, an above-the-median H2T level was significantly associated with a shorter TTBM (hazard ratio, [HR], 2.4; p = .005), whereas this was not true for the median HER-2/CEP17 ratio by FISH (p = .4). Correlation between a continuous H2T level and TTBM was confirmed on multivariate analysis (HR, 3.3; p = .024). CONCLUSIONS: These data reveal a strong relationship between the quantitative HER-2 protein expression level and the risk for brain relapse in HER-2+ advanced breast cancer patients. Consequently, quantitative assessment of HER-2 protein expression may inform and facilitate refinements in therapeutic treatment strategies for selected subpopulations of patients in this group.

Correlation between MET gene copy number by silver in situ hybridization and protein expression by immunohistochemistry in non-small cell lung cancer.

PURPOSE: The MET receptor is involved in the pathogenesis and progression of non-small cell lung cancer (NSCLC). Clinical trials with MET inhibitors in NSCLC are planned with patient selection based on immunohistochemistry (IHC) and/or gene copy number assessment. Therefore, a detailed understanding of relationship between these markers and prognosis is essential. METHODS: This study included tumors from 189 patients with NSCLC who underwent pulmonary resection (median follow-up, 5.3 years). MET expression was evaluated by IHC on tissue microarrays and scored according to hybrid (H) score (range: 0-400) and by scoring system used in the MetMAb trial (≥ 50% of cells with moderate or strong staining). MET gene copy number was assessed by silver in situ hybridization (n =140 patients). RESULTS: Median MET IHC H score was 60 (range: 0-400; n =174). There were no associations between clinical and pathological characteristics, disease-free survival, and overall survival according to median value (p =0.36 and p =0.38, respectively), or other cut-points. According to MetMAb scoring criteria, IHC positivity rate was 25%, again with no associations to clinicopathological features or survival. In 140 tumors evaluable for MET copy number, 3 (2.1%) showed gene amplification and 14 (10%) had tumors with average of 5 or more copies per nucleus. There were no associations of MET copy number with clinical characteristics, disease-free survival, or overall survival with any analyzed cut-points. Correlation between MET copy number and protein expression was significant (Pearson's r =0.42, p < 0.0001). CONCLUSIONS: There is a significant correlation between MET protein expression and MET gene copy number in operable NSCLC, but neither is associated with prognosis.

Insulin-like growth factor receptor 1 (IGF1R) gene copy number is associated with survival in operable non-small-cell lung cancer: a comparison between IGF1R fluorescent in situ hybridization, protein expression, and mRNA expression.

PURPOSE: The purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non-small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis. PATIENTS AND METHODS: One hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181). RESULTS: IGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis. CONCLUSION: IGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.

Risk factors for brain relapse in HER2-positive metastatic breast cancer patients.

Brain relapse is a common occurrence in HER2-positive breast cancer patients. However, the factors determining the risk of brain metastasis in these patients remain to be established. The aim of this study was to assess the impact of particular clinical and pathological factors on the risk of brain relapse in HER2-positive advanced breast cancer patients. The study group included 264 consecutive HER-2 positive metastatic breast cancer patients, most of whom (210; 80%) were administered trastuzumab, usually in combination with chemotherapy. Time from the diagnosis to distant relapse ranged from 0 to 142 months (median 16 months). The most common dominant site of metastatic disease was viscera (80%), followed by soft tissue (11%) and bones (10%). After a median follow-up of 3.1 years, the symptomatic brain relapse occurred in 103 patients (39%). Median time from treatment dissemination to brain relapse was 15 months (range, 0-81 months), and the cumulative 1-year, 3-year and 5-year risk of brain relapse was 17, 42 and 55%, respectively. The average annual risk of brain relapse for surviving patients during consecutive 7 years of follow-up was 10.0% (95% CI, 6.6-13.5%). In the univariate analysis the only variable significantly related to the increased risk of brain relapse was time from initial diagnosis to distant relapse shorter than 2 years (HR = 1.55, 95% CI, 1.03-2.33, P = 0.034). Patients with dominant site of disease in soft tissue or bones tended to have lower risk of relapse (HR = 0.54 and 0.62; P = 0.098 and 0.203, respectively) compared to patients with visceral metastases. Treatment with trastuzumab was not associated with reduced risk of brain relapse (HR = 0.91, 95% CI, 0.47-1.77, P = 0.78). In the multivariate analysis, time from initial diagnosis to distant relapse shorter than 2 years remained the only significant variable related to increased risk of brain relapse (adjusted HR = 1.62, 95% CI, 1.07-2.44; P = 0.022). HER2-positive breast cancer patients remain at high and continuous risk of brain relapse for a prolonged period of time after diagnosis of disease dissemination. Short time from initial diagnosis to distant relapse is related to increased risk of brain relapse. Molecular predictors are sorely needed to better characterize patients with high probability of early brain relapse.