Predictors of recurrence in breast cancer patients with pathological partial response.

OBJECTIVE: Patients with residual disease after neoadjuvant chemotherapy have a relative risk of developing recurrence. This study investigates the risk factors for recurrence in locally advanced breast cancer patients with residual disease and evaluates survival analysis. METHODS: This is a retrospective, single-center study. Breast cancer patients who failed to achieve a pathological complete response after neoadjuvant chemotherapy were included. Demographic, clinicopathological, and treatment characteristics were evaluated to identify predictive factors of recurrence and survival analysis. RESULTS: We included 205 patients in this study. After a median of 31 months of follow-up, 10 patients died, and 20 developed distant metastasis. Disease-free survival and disease-specific survival were 73.8% and 83.1%, respectively. Lymphovascular invasion and non-luminal subtype were independent predictors of locoregional recurrence. In situ carcinoma, lymphovascular invasion, ypTIII stage, and non-luminal molecular subtypes were independent predictors of disease-free survival. The only independent factor affecting disease-specific survival was cNII-III. The number of involved lymph nodes was an independent predictor of disease-free survival in patients without complete axillary response. CONCLUSION: Factors affecting disease-specific survival and disease-free survival were cNII-III and the number of involved lymph nodes, respectively. Patients with non-luminal, large residual tumors with in situ carcinoma, lymphovascular invasion, clinically positive axilla, and residual nodal involvement have a high relative risk for recurrence and may benefit from additional treatments.

The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters.

Background: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers. Aim: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas. Materials and Methods: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs. Statistical Analysis: Data was analyzed with t-tests and Chi-square tests. Kaplan-Meier and Log-rank tests were used for survival analysis. Results: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs. Conclusions: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.

The roles of 68 Ga-PSMA PET/CT and 18 F-FDG PET/CT imaging in patients with triple-negative breast cancer and the association of tissue PSMA and claudin 1, 4, and 7 levels with PET findings.

AIM: Aim of study is to compare the results of Gallium-68-prostate-specific membrane antigen ( 68 Ga-PSMA) and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography(PET)/computed tomography (CT), to evaluate the correlation between PET findings and the level of PSMA, Claudin (Clau) 1, 4, and 7 receptors obtained by immunohistochemical (IHC) analysis, and to determine potential predictive and prognostic values in TNBC. METHODS: Forty-seven lesions of 42 subjects diagnosed TNBC both underwent PET/CT scan for preoperative staging/restaging were prospectively included study. PSMA, Clau 1, 4, and 7 expressions were IHC evaluated from the biopsy samples of the primary tumor (PT). Maximum standardized uptake value(SUV max) of the PT, lymph node, and distant organ metastases (DOMs) on 18 F-FDG and 68 Ga-PSMA PET/CT were compared with PSMA, Clau 1, 4, and 7 receptor expressions. RESULTS: IHC analyses on 29 BC lesions to demonstrate Clau expression showed 86% (25/29) Clau 1, 86% (25/29) Clau 4, 45% (13/29) Clau 7, and 48% (14/29) PSMA-positive. The mean DOM (SUVmax) was 15.5 ± 11.6 for 18 F-FDG and 6.0 ± 2.9 for 68 Ga-PSMA. Axial diameter of BC PT had a significant positive correlation with 18 F-FDG SUVmax, 68 Ga-PSMA SUVmax, and PSMA scores. BC lesions 68 Ga-PSMA SUVmax had a significant negative correlation with the Ki-67 index. Axial diameter of the primary tumor had significant negative correlation with Clau 7 scores ( r = -0.409, P = 0.034). Absence of Clau 1 expression found to significantly increase the rate of DOM (100% vs. 28%) ( P = 0.014). All patients with axillary lymph node (ALN) metastases ( n = 17, 100%) exhibited Clau 4 positivity ( P = 0.021). The presence of PSMA expression observed to significantly increase the rate of ALN metastases (64.7% vs. 25%) ( P = 0.035). CONCLUSION: Confirming PSMA expression with PET imaging would be significant as PSMA, a theranostic agent, may be a considerable potential agent for radionuclide treatment strategies, in addition to its additional diagnostic contribution to FDG, especially in patients with metastatic TNBC, which is an aggressive, heterogeneous disease.

Radiomics of locally advanced rectal cancer: machine learning-based prediction of response to neoadjuvant chemoradiotherapy using pre-treatment sagittal T2-weighted MRI.

PURPOSE: Variable response to neoadjuvant chemoradiotherapy (nCRT) is observed among individuals with locally advanced rectal cancer (LARC), having a significant impact on patient management. In this work, we aimed to investigate the potential value of machine learning (ML)-based magnetic resonance imaging (MRI) radiomics in predicting therapeutic response to nCRT in patients with LARC. MATERIALS AND METHODS: Seventy-six patients with LARC were included in this retrospective study. Radiomic features were extracted from pre-treatment sagittal T2-weighted MRI images, with 3D segmentation. Dimension reduction was performed with a reliability analysis, pair-wise correlation analysis, analysis of variance, recursive feature elimination, Kruskal-Wallis, and Relief methods. Models were created using four different algorithms. In addition to radiomic models, clinical only and different combined models were developed and compared. The reference standard was tumor regression grade (TRG) based on the Modified Ryan Scheme (TRG 0 vs TRG 1-3). Models were compared based on net reclassification index (NRI). Clinical utility was assessed with decision curve analysis (DCA). RESULTS: Number of features with excellent reliability is 106. The best result was achieved with radiomic only model using eight features. The area under the curve (AUC), accuracy, sensitivity, and specificity for validation were 0.753 (standard deviation [SD], 0.082), 81.1%, 83.8%, and 75.0%; for testing, 0.705 (SD, 0.145), 73.9%, 81.2%, and 57.1%, respectively. Based on the clinical only model as reference, NRI for radiomic only model was the best. DCA also showed better clinical utility for radiomic only model. CONCLUSIONS: ML-based T2-weighted MRI radiomics might have a potential in predicting response to nCRT in patients with LARC.

Factors affecting pathological complete response after neoadjuvant chemotherapy in breast cancer: a single-center experience.

OBJECTIVE: The aim of this study was to examine the characteristics of patients admitted to our hospital with a diagnosis of breast cancer who reached pathological complete response after being operated following eight cycles of neoadjuvant chemotherapy. METHODS: Between 2015-2020, patients with pathological complete response who were operated on after neoadjuvant chemotherapy and sent to our clinic for radiotherapy were evaluated. RESULTS: The median age of the patients was 51 years. The most common histological type was invasive ductal cancer. The number of pathological complete response patients was 74 (28%), and the number of non-pathological complete response patients was 188 (72%). Patients with pathological complete response had a smaller tumor diameter than the non-pathological complete response group (p=0.001). For pathological complete response, T1 stage, N1 stage, NG 3, Ki-67 >20%, negative estrogen receptor, negative progesterone receptor, positive Cerb-B2, and adding trastuzumab to chemotherapy were statistically significant (p<0.05). Before neoadjuvant chemotherapy, stage T1-T2 (p=0.036), LN0-1 (p=0.026), Cerb-B2 positivity (p=0.025), and an initial nuclear grade of three (p=0.001) were found to be the factors affecting pathological complete response. CONCLUSIONS: With neoadjuvant chemotherapy, the size of locally advanced tumors decreases, allowing breast conserving surgery. The neoadjuvant chemotherapy response can be used as an early indicator of the prognosis of patients with breast cancer. Today, neoadjuvant chemotherapy is also used for patients with early-stage, operable breast cancer because it has been shown in many studies that reaching pathological complete response is associated with positive long-term results. If we can identify patients who have reached pathological complete response before neoadjuvant chemotherapy, we think we can also determine a patient-specific treatment plan at the beginning of treatment.

The Expression of Galectin-3 in Tumor and Cancer-Associated Fibroblasts in Invasive Micropapillary Breast Carcinomas: Relationship with Clinicopathologic Parameters.

OBJECTIVE: Galectin-3 affects tumor progression and cell surface polarization by expressing from the tumor and cancer-associated fibroblasts (CAFs). Therefore, it may have a role on micropapillary carcinomas (IMPC), which have characteristic morphological features. The aim was to investigate the expression levels of Galectin-3 within tumor and peritumoral CAFs in IMPC, and to compare with expression in invasive ductal carcinomas (IDC). MATERIALS AND METHODS: Hematoxylin and Eosin-stained preparations of resection materials examined between 2010-2016 were re-evaluated. Thirty-four IMPC cases and 34 IDC cases with similar molecular subtype distribution to IMPC were compared. Galectin-3 levels were evaluated with a calculated H-score in tumor and semi-quantitatively in CAFs. RESULTS: While tumoral Galectin-3 expression levels were higher in IMPCs compared to IDCs, there was no difference for Galectin-3 expression in CAFs between the two histologic types. However, there was no significant relationship between tumoral Galectin-3 expression and clinicopathological parameters in IMPCs. When the subjects were divided into two groups, depending on their Galectin-3 status regardless of histological types, the loss of Galectin-3 expression in tumor was found to be related to larger tumor size/advanced pT stage and a greater number of metastatic nodes. Additionally, expression of Galectin-3 in CAFs was found to be associated with distant metastasis. CONCLUSION: IMPC showed prominent Galectin-3 expression in tumor compared to IDC. However, independent from the histological type, whereas the loss of Galectin-3 expression in tumor showed an association with larger tumor size and higher number of metastatic axillary lymph nodes, the presence of Galectin-3 expression in CAFs showed an association with distant metastasis.

Factors affecting pathological complete response after neoadjuvant chemotherapy in breast cancer: a single-center experience

SUMMARY OBJECTIVE: The aim of this study was to examine the characteristics of patients admitted to our hospital with a diagnosis of breast cancer who reached pathological complete response after being operated following eight cycles of neoadjuvant chemotherapy. METHODS: Between 2015-2020, patients with pathological complete response who were operated on after neoadjuvant chemotherapy and sent to our clinic for radiotherapy were evaluated. RESULTS: The median age of the patients was 51 years. The most common histological type was invasive ductal cancer. The number of pathological complete response patients was 74 (28%), and the number of non-pathological complete response patients was 188 (72%). Patients with pathological complete response had a smaller tumor diameter than the non-pathological complete response group (p=0.001). For pathological complete response, T1 stage, N1 stage, NG 3, Ki-67 >20%, negative estrogen receptor, negative progesterone receptor, positive Cerb-B2, and adding trastuzumab to chemotherapy were statistically significant (p<0.05). Before neoadjuvant chemotherapy, stage T1-T2 (p=0.036), LN0-1 (p=0.026), Cerb-B2 positivity (p=0.025), and an initial nuclear grade of three (p=0.001) were found to be the factors affecting pathological complete response. CONCLUSIONS: With neoadjuvant chemotherapy, the size of locally advanced tumors decreases, allowing breast conserving surgery. The neoadjuvant chemotherapy response can be used as an early indicator of the prognosis of patients with breast cancer. Today, neoadjuvant chemotherapy is also used for patients with early-stage, operable breast cancer because it has been shown in many studies that reaching pathological complete response is associated with positive long-term results. If we can identify patients who have reached pathological complete response before neoadjuvant chemotherapy, we think we can also determine a patient-specific treatment plan at the beginning of treatment.

Effective of Pre-operative 2-Deoxy-2-[fluorine-18] fluoro-d-glucose/Positron Emission Tomography/Computed Tomography in the Determination of Boost Volume in Adjuvant Radiotherapy after Breast-conserving Surgery.

OBJECTIVES: Determining boost volume (BV) during breast radiotherapy can be challenging at times. Therefore, surgical clips are now being widely used. At times, when surgical clips are inadequate in determining the BV, other additional imaging methods are required. In the present study, we aimed to demonstrate that pre-operative positron emission tomography/computed tomography (PET-CT) can be used to determine the BV after a breast-conversing surgery. METHODS: We selected thirty patients who underwent breast-conserving surgery with surgical clips and had preoperative Fluorine-18-Fluorodeoxyglucose PET (18 FDG PET/CT). The BV in planning tomography (CT) and primary tumor volume (TV) in pre-operative F-18 FDG PET/CT was contoured by a radiation oncologist. These two volumes were superposed using rigid image fusion. In every patient, two BVs were measured. The mean shift between the two volumes by the calculation of the center of mass and percentage of the PET-CT TV (PET-CT TV) in planning the BV (planning target volume [PTV]-BV) was calculated. RESULTS: The median age was 52 years (range 25-72 years). The pre-operative PET-CT TV median was 8.89 cm3 (range 1.00-64.30 cm3). The median PTV-BV was 62.92 cm3 (12.57-123.07 cm3). The median shifts between the center of volumes were 1.76 cm (range 0.90-3.50) in X(coronal), 1.73 cm (range 0.60-3.60) in the Y(axial), and 1.20 cm (0.40-2.80) in the Z(sagittal) directions, respectively. The shifts in these three planes were determined to be statistically significant (p<0.001). The percent volume of PET-CT TV included PTV TV, ranging from 35% to 100% (mean 54%, standard deviation 29.53) and 100% in two out of 31 patients. CONCLUSION: Our study has shown that pre-operative PET-CT cannot be used to determine the BV in patients who replaced surgical clips and had undergone breast-conserving surgery. To define a more accurate BV, surgical clips should be placed in four planes, and more PTV margins should be given in treatment planning.

Alternative volumetric PET pjmirometers for evaluation of breast cancer cases with 18F-FDG PET/CT imaging: Metabolic tumour volume and total lesion glycolysis.

INTRODUCTION: We aimed to investigate the prognostic and clinical values of two volumetric PET pjmirometers used in conjunction with SUVmax at different thresholds in invasive ductal carcinoma (IDC). METHODS: A total of 139 metastatic IDC BC who underwent 18F-FDG PET/CT imaging were included to study. MTV and TLG (40%, 50%, 60% and 70%) used in conjunction with primary tumour SUVmax . Nodal involvement, distant metastasis, ER, PR, Ki-67 expression and survival data evaluated by comparing FDG PET pjmirometers. RESULTS: Mean ± SD SUVmax of lesions (n = 139) was 13.97 ± 9.21. Primary tumour 18F-FDG uptake associated increased tumour diameter (>2 cm), high Ki-67 (>15%) and distant organ metastasis (DOM) (P = 0.015, 0.005 and 0.016, respectively). There was significant association between molecular subtypes and SUVmax (P = 0.002). High MTV associated with tumour diameter (MTV 40-70%), axillary lymph node (ALN) diameter (MTV 40-70%), and distant nodal metastasis (DNM) (MTV 50-70%). High TLG associated with tumour diameter (TLG 40-70%), high Ki-67 (TLG 40-70%), ALN metastasis (TLG 40%), ALN diameter (TLG 40-70%) and DNM (TLG 40-70%). Median survival found shorter in DOM patients (P = 0.030, Log Rank = 0.110). CONCLUSION: We think evaluation of MTV and TLG at different thresholds in addition to SUVmax would enhance diagnostic and prognostic value of 18F-FDG PET/CT, and thus contribute to disease management.

The Effect of Indicators of Systemic Inflammatory Response on Survival in Glioblastoma Multiforme.

AIM: To evaluate the prognostic value of preoperative neutrophil-to-lymphocyte ratio and platelet-lymphocyte ratio in glioblastoma multiforme patients. MATERIAL AND METHODS: A total of 75 patients retrospectively analysed. The complete blood count of the patients was analysed before surgery. In our study, cut-off values for PLR 150 (platelet-lymphocyte ratio) and NLR 4 (neutrophil-to-lymphocyte ratio) were found to be significant by creating the ROC curve. Overall survival (OS) was calculated from surgery to death or the last contact. Progression-free survival (PFS) was calculated from surgery to progression. The last follow-up was November 2018. RESULTS: The median OS was significantly shorter in PLR > 150 patients (p=0.005; 10 vs 17 months). And the median OS was significantly shorter in NLR > 4 patients too (p=0.010; 11 vs 17 months). In multivariate analysis, Karnofsky performance score < 70 (HR:2.96, 95% CI:1.68-5.21; p < 0.001), type of surgical resection (HR:2.32, 95% CI:1.35-3.98; p=0.002) were statistically significant for PFS. In multivariate analysis, KPS < 70 (HR:2.72, 95% CI:1.30-5.67; p < 0.007), type of surgical resection (HR:2.09, 95% CI:1.10- 3.95; p=0.023), NLR > 4 (HR:2.14, 95% CI:1.11-4.14; p=0.023) were statistically significant for OS were found to be independent prognostic factor. CONCLUSION: The presence of 70 < KPS and type of surgical resection in patients with GBM had a negative effect on PFS. NLR > 4, 70 < KPS, type of surgical resection were independent prognostic factors that negatively affect for the OS.