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.

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.

The correlation between skeletal muscle index and anxiety in patients with lung cancer on the first day of chemotherapy.

Aim: To evaluate the relationship between anxiety and skeletal muscle index (SMI) levels in lung cancer patients on the first day of chemotherapy. Materials & methods: This cross-sectional study included 108 patients. We analyzed patient characteristics, SMI levels, pain status and predicted anxiety factors. Results: Anxiety was detected in 61% of patients. SMI levels were significantly lower in the high anxiety group than the low anxiety group (p < 0.001). A significant correlation was observed between anxiety and SMI levels (r = -0.292; p = 0.002). Anxiety levels were significantly correlated with trait anxiety (r = 0.618; p < 0.001) and visual analog scale-pain (r = 0.364; p < 0.001). SMI (odds ratio: 0.94), trait anxiety (odds ratio: 1.12) and visual analog scale pain (odds ratio: 1.28) were independent risk factors for anxiety after adjusting for sex, stage and Eastern Cooperative Oncology Group performance status. Conclusion: Our study highlighted that higher anxiety scores were significantly correlated with lower SMI levels. We found that SMI, pain and trait anxiety were independent risk factors for anxiety.

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.

Breast Cancer Patients with Brain Metastases: A Cross-Sectional Study.

The prognosis of breast cancer patients with brain metastasis is poor. It was aimed to define the clinicopathological features of breast cancer patients with brain metastases and to determine the risk factors and survival outcomes associated with brain metastasis. This is a single-center, retrospective, cross-sectional study. A total number of 127 patients diagnosed with breast cancer and who developed brain metastasis between January 2011 and March 2021 were retrospectively analyzed. The survival and clinicopathological data of these patients according to 4 biological subtypes were evaluated (luminal A, luminal B, HER-2 overexpressing, and triple-negative). The median overall survival for all patients was 45.6 months. The median time from the diagnosis of breast cancer to the occurrence of brain metastasis was 29.7 months, and the median survival time after brain metastasis was 7.2 months. The time from the diagnosis of breast cancer to brain metastasis development was significantly shorter in HER-2 overexpressing and triple-negative subtypes than in luminal A and B subtypes. The median time from breast cancer diagnosis to brain metastasis was 33.5 months in luminal A, 40.6 months in luminal B, 16.8 months in HER-2 overexpressing, and 22.8 months in the triple-negative groups (p=0.003). We found the worst median survival after brain metastasis in the triple-negative group with 3.5 months. Early and close surveillance of high-risk patients may help early diagnosis of brain metastasis and may provide to perform effective treatments leading to longer overall survival times for this patient population.

The real-life efficacy and safety of osimertinib in pretreated advanced non-small cell lung cancer patients with T790M mutation: a Turkish Oncology Group Study.

INTRODUCTION: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose disease progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation. MATERIALS AND METHODS: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. RESULTS: Of 163 patients, 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13-month follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. CONCLUSION: Osimertinib is a highly effective option in second- or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.

A case report of fulminant hepatitis due to ribociclib with confirmed by liver biopsy in breast cancer.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer in women worldwide. Ribociclib is now frequently used in the treatment of metastatic hormone-positive and human epidermal growth factor receptor 2 (HER 2)-negative breast cancer. CASE REPORT: A 54-year-old woman with breast cancer presented at a clinic in November 2017 with multiple lung and bone metastases. After receiving multiple lines of treatment due to disease progression, ribociclib and fulvestrant were initiated. Grade 4 toxicity was observed due to ribociclib during follow-up, and ribociclib was discontinued permanently.Management & Outcome: Given that liver transaminases and bilirubin elevation persisted despite discontinuation of the treatment, other reasons for liver toxicity were investigated. Abdominal MRI showed no liver metastases, although there was acute hepatitis. A liver biopsy was performed to determine the etiology. The pathology result was compatible with drug-induced acute fulminant toxic hepatitis. After liver biopsy, prednisolone treatment was initiated, after which the laboratory findings normalized. DISCUSSION: Although there are reported cases showing improvement in liver enzymes after ribociclib discontinuation, in our case, no recovery from hepatotoxicity was noticed. The treatment was changed to another hormonal pathway therapy option, exemestane. To the best of our knowledge, this is the first case in the literature reporting this rare side effect of ribociclib, which is a liver biopsy-proven fulminant hepatitis.

Metastatic Breast Carcinoma Mimicking Urothelial Carcinoma.

Besides being the most frequently diagnosed cancer in women, breast cancer is the main cause of cancer-related deaths in this group of patients. Breast cancer frequently metastasizes to bone, lung, brain, and liver. Renal metastasis from the breast is extremely rare. Here we aimed to report a case of breast cancer with metastasis to bone and left renal pelvis. A 58-year old woman with a mass lesion in the left renal pelvis that mimicked urothelial carcinoma was referred to our clinic. The left nephroureterectomy procedure was performed, and the pathology revealed that a renal pelvis metastasis secondary to breast cancer.

Anxiety levels of breast cancer patients in Turkey during the COVID-19 pandemic.

Aim: To assess the anxiety levels of breast cancer patients during the COVID-19 pandemic. Materials & methods: A total of 298 patients completed the State-Trait Anxiety Inventory (STAI-S and STAI-T) and the Visual Analogue Scale for Anxiety (VAS) and VAS for Anxiety in COVID-19 (VAS-CoV). Results: 144 patients were in the high anxiety category for STAI-S, and 202 patients were in the high anxiety category for STAI-T. STAI-T score was significantly high in the metastatic group (p = 0.017). VAS-CoV score in the hormonotherapy group was significantly higher than in the no-treatment group (p = 0.023). There was a positive correlation between VAS-CoV and VAS levels (r = 0.708, p < 0.001), VAS-CoV and STAI-S and STAI-T scores (r = 0.402, p < 0.001; r = 0.185, p = 0.001, respectively), and a negative correlation between education years and STAI-T scores (r = -0.172, p = 0.003). Conclusion: The COVID-19 pandemic is related to high anxiety levels in breast cancer patients.

Lay abstract COVID-19 pandemic is related to rapidly rising anxiety levels worldwide. Because of the high mortality of COVID-19 in cancer patients, changing treatment routines and disruptions of the healthcare system, cancer patients are the most affected population in this situation. Anxiety among females and breast cancer patients tend to be high, although anxiety levels in cancer patients during the pandemic period varies according to the cancer type, treatment status and sociodemographic factors. This study assessed the effect of the COVID-19 pandemic on breast cancer patients' anxiety levels according to treatment status and stage of the disease. A total of 298 breast cancer patients completed the universally validated anxiety questionnaires. Results demonstrated high trait anxiety in breast cancer patients, particularly in the metastatic group. The current findings highlighted the importance of intensive assessment and close monitoring of breast cancer patients' psychological situations. It is crucial to provide psychological support to breast cancer patients to contribute to both treatment and follow-up processes during the pandemic.

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.

Systemic Inflammatory Markers for Prediction of Bevacizumab Benefit in Glioblastoma Multiforme.

OBJECTIVE:  To evaluate the predictive significance of systemic inflammation markers (SIMs) in patients with glioblastoma multiforme (GBM), who were treated with bevacizumab (Beva). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The study was conducted at the Bezmialem Vakif University School of Medicine Hospital, Istanbul, Turkey, from January 2014 to September 2019. METHODOLOGY: A total of 107 patients, 49 (45.8%) female and 58 (54.2%) male, were retrospectively included in the study. The cut-off values for the SIMs-C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte (NLR) platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIII))-were defined by receiver operating characteristic (ROC) analysis. Overall survival (OS) was plotted using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was performed for univariate and multivariate analyses. RESULTS: ROC analysis was performed to determine the optimal prognostic value of each parameter. CAR: 1.32, NLR: 2.9, PLR: 159, and SIII: 785 were determined as cut-off values for predicting OS based on the areas under the curve (AUC) in the ROC analysis. CAR at 0.626, had sensitivity of 67%, and specificity of 71% (p=0.129); NLR at 0.725 had sensitivity of 67%, and specificity of 79% (p=0.007); PLR at 0.675 had sensitivity of 67%, and specificity of 64% (p=0.036); and SIII at 0.685, had sensitivity of 56%, and specificity of 71% (p=0.026). A multivariate analysis demonstrated that CAR (p=0.006) and PLR (p=0.024) were independent prognostic factors for OS in patients with GBM, treated by Beva. CONCLUSION:  The present study's findings suggest that pretreatment CAR and PLR might be an independent predictive marker for patients with GBM, who are treated by Beva. Key Words: C-reactive protein-to-albumin ratio (AR), Glioblastoma multiforme, Neutrophil-to-lymphocyteratio (NLR), Platelet-to-lymphocyte ratio (PLR), Predictive score.

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.