Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

Differentiation of lung and breast cancer brain metastases: Comparison of texture analysis and deep convolutional neural networks.

PURPOSE: Metastases are the most common neoplasm in the adult brain. In order to initiate the treatment, an extensive diagnostic workup is usually required. Radiomics is a discipline aimed at transforming visual data in radiological images into reliable diagnostic information. We aimed to examine the capability of deep learning methods to classify the origin of metastatic lesions in brain MRIs and compare the deep Convolutional Neural Network (CNN) methods with image texture based features. METHODS: One hundred forty three patients with 157 metastatic brain tumors were included in the study. The statistical and texture based image features were extracted from metastatic tumors after manual segmentation process. Three powerful pre-trained CNN architectures and the texture-based features on both 2D and 3D tumor images were used to differentiate lung and breast metastases. Ten-fold cross-validation was used for evaluation. Accuracy, precision, recall, and area under curve (AUC) metrics were calculated to analyze the diagnostic performance. RESULTS: The texture-based image features on 3D volumes achieved better discrimination results than 2D image features. The overall performance of CNN architectures with 3D inputs was higher than the texture-based features. Xception architecture, with 3D volumes as input, yielded the highest accuracy (0.85) while the AUC value was 0.84. The AUC values of VGG19 and the InceptionV3 architectures were 0.82 and 0.81, respectively. CONCLUSION: CNNs achieved superior diagnostic performance in differentiating brain metastases from lung and breast malignancies than texture-based image features. Differentiation using 3D volumes as input exhibited a higher success rate than 2D sagittal images.

Prognostic significance of HER2 loss after HER2-targeted neoadjuvant treatment in patients with HER2-positive locally advanced breast cancer.

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25-30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

Is the Duration of Temozolomide Predictive for Sequential Bevacizumab Treatment Responses in the Glioblastoma Multiforme Cancer Setting?

OBJECTIVE: To evaluate the predictive significance of the duration of temozolomide (TMZ) in patients with glioblastoma multiforme (GBM) who were treated with bevacizumab (Beva) as second-line setting. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Bezmialem Vakif University School of Medicine Hospital, Istanbul, Turkey, from January 2014 to September 2020. METHODOLOGY: A total of 109 patients, 47 (43.1%) females and 62 (56.9%) males, were retrospectively included in the study. All patients received TMZ as first-line and Beva as second-line treatment. Kaplan-Meier method and Cox regression model were performed for survival and univariate/multivariate analyses, respectively. RESULTS: Patients treated with first-line TMZ were divided into two groups according to the PFS. Group 1 is <9 months and group 2 is ≥9 months. Overall survival (OS) of group 1 and group 2 patients was evaluated  after the initiation of second-line bevacizumab treatment. The OS in group 1 was 7.8 months (6.9-8.6, 95% CI), and group 2 was eight months (6.4-9.5, 95% CI), but it was statistically non-significant (p = 0.837). CONCLUSION: Duration of first-line TMZ treatment was not a predictor for OS of the GBM patients, who were treated with Beva as second-line setting. Key Words: Bevacizumab, Duration of treatment, Glioblastoma multiforme, Predictive score, Temozolomide.

Relationship with Programmed Cell Death Ligand 1 (PD-L1) and DTI Features in Brain Metastases of Non-small Cell Lung Cancer: A Preliminary Study.

OBJECTIVE: The purpose of the study was to determine DTI properties of brain metastases in subjects with Non-Small Cell Lung Carcinoma (NSCLC) to evaluate whether there was a correlation between DTI findings and Programmed Cell Death Ligand-1 (PD-L1). METHODS: The study population (n:22) was assigned to PD-L1 negative (Group 1: PD-L1 expression<% 50) (n=11) or positive (Group 2: PD-L1 expression ≥%50) (n=11). We compared ADC and FA values measured from the enhanced solid metastases and peritumoral edema area with PD-L1 protein status. RESULTS: The mean ADC values were lower in group 2 compared to group 1. The peritumoral ADC values were higher in group 2 compared to group 1. Mean peritumoral edema FA values were lower in group 2 compared to group 1. The peritumoral edema nADC values were higher in group 2 compared to group 1. As PD-L1 expression frequency increased, ADC values in the peritumoral edema area increased and FA values decreased. CONCLUSION: We thought that the existence of PD-L1 protein does not affect ADC and FA values of brain metastasis (BM) originating from NSCLC. DTI characteristics of the peritumoral edema area could be a guide in determining the PD-L1 protein status of brain metastases of NSCLC. The relationship between PD-L1 expression status and DTI features in BM from NSCLC could help us to have an idea regarding the response to immunotherapy.

Is lymph node dissection necessary for staging while undergoing nephrectomy in patients with renal cell carcinoma?

OBJECTIVE: The essential treatment for patients with renal cell carcinoma is nephrectomy. As no lymph node dissection (LND) could be performed in the majority of these patients, healthy staging could not be carried out. In this study, we investigated the impact of LND during nephrectomy on patient survival. METHODS: A total of 181 patients-58 (32%) were female and 123 (68%) were male-were included in the study. Median follow-up period was 48 months. The patients were separated into 4 groups according to their stage during diagnosis; group 1 (T1-3N0M0), group 2 (T1-3NXM0), group 3 (T1-3N1M0), and group 4 (T1-4N0/XM1). The disease-free survival of nonmetastatic patients and the overall survival of all groups were calculated. RESULTS: Mean age was 58.4 ± 12.0 years. Median survival for Group 1 could not be reached. Median survival was 89 months in Group 2, 50 months in Group 3, and 39 months in Group 4 (P <0.001). There was no statistically significant difference between the N1 and M1 groups (P = 0.297). For the NX patient group without LND, median survival was 89 months, which is worse than the N0 group and better than the N1 group (P = 0.002). CONCLUSIONS: Our study presumes that the patients without LND are not staged sufficiently, NX patients have worse survival rates when compared with N0 patients, node-positive patients have poor survival rates as do the metastatic patients, and it should be defined as TNM stage4.