Determining a musculoskeletal system's pre-stretched state using continuum-mechanical forward modelling and joint range optimization.

The subject-specific range of motion (RoM) of a musculoskeletal joint system is balanced by pre-tension levels of individual muscles, which affects their contraction capability. Such an inherent pre-tension or pre-stretch of muscles is not measureable with in vivo experiments. Using a 3D continuum mechanical forward simulation approach for motion analysis of the musculoskeletal system of the forearm with 3 flexor and 2 extensor muscles, we developed an optimization process to determine the muscle fibre pre-stretches for an initial arm position, which is given human dataset. We used RoM values of a healthy person to balance the motion in extension and flexion. The performed sensitivity study shows that the fibre pre-stretches of the m. brachialis, m. biceps brachii and m. triceps brachii with 91 % dominate the objective flexion ratio, while m. brachiradialis and m. anconeus amount 7.8 % and 1.2 % . Within the multi-dimensional space of the surrogate model, 3D sub-spaces of primary variables, namely the dominant muscles and the global objective, flexion ratio, exhibit a path of optimal solutions. Within this optimal path, the muscle fibre pre-stretch of two flexors demonstrate a negative correlation, while, in contrast, the primary extensor, m. triceps brachii correlates positively to each of the flexors. Comparing the global optimum with four other designs along the optimal path, we saw large deviations, e.g., up to 15 ∘ in motion and up to 40% in muscle force. This underlines the importance of accurate determination of fibre pre-stretch in muscles, especially, their role in pathological muscular disorders and surgical applications such as free muscle or tendon transfer.

Comparison of three equations for estimating glomerular filtration rate as predictors of cisplatin-related acute kidney injury in lung cancer patients with normal renal function.

OBJECTIVE: Cisplatin-associated acute kidney injury is a common clinical event that causes increased morbidity and mortality in cancer patients even if they are categorized as having normal functioning kidneys. We aimed to determine predictive factors that can predict acute kidney injury associated with cisplatin therapy in patients with normal renal function by comparison of pre-chemotherapy estimated glomerular filtration rates calculated separately by Cockcroft and Gault (CG), the Modification of Diet in Renal Disease (MDRD), and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and accompanying patient-associated factors. MATERIALS AND METHODS: A total of 200 patients diagnosed with lung cancer and determined to have normal functioning kidneys and considered cisplatin eligible by the attending physician before chemotherapy were included in this retrospective study. Acute kidney injury after cisplatin chemotherapy (c-AKI) was determined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03. Pre-chemotherapy serum laboratory parameters and clinico-histopathological characteristics of patients were recorded from the hospital electronic system. The optimal cut-off for eGFR methods was determined by the area under the receiver operating characteristic curve (ROC-AUC) analysis. Predictive factor analysis for c-AKI was performed by regression analyses. RESULTS: C-AKI developed in 39 (19.5%) patients. In the univariate analysis, a significant correlation was observed between c-AKI and high body mass index (BMI) before treatment, older age (>62.5), female gender, eGFR by MDRD (≤94.5 mL/min) and eGFR by CKD-EPI (≤91.5 mL/min). There was no relation between eGFR by CG and c-AKI. Two different multivariate models were established. Model 1 showed that female gender (odds ratio [OR] =4.90, 95% confidence interval [CI]: 1.52-15.79, P = 0.008) and eGFR by MDRD less than or equal to 94.5 mL/min (OR = 3.52, 95% CI: 1.68-7.38, P = 0.001) were predictive markers for c-AKI. In Multivariate Model 2, female gender (OR = 5.51, 95% CI: 1.70-17.83, P = 0.004) and eGFR by CKD-EPI less than or equal to 91.5 mL/min (OR = 3.52, 95% CI: 1.67-7.42, P = 0.001) were found to be predictive markers for c-AKI. CONCLUSIONS: This study revealed that eGFR calculated based on MDRD (≤94.5 mL/min/m2) or CKD-EPI (≤91.5 mL/min/m2) before chemotherapy indicates a strong tendency for c-AKI. In addition, we detected a high risk of c-AKI for females compared to their counterparts. Although eGFR 60 mL/min is considered the threshold level to accept patients as cisplatin-eligible, we recommend close follow-up of high-risk patients for cisplatin nephrotoxicity we detected in our models.

Efficacy of Neoadjuvant Chemotherapy in Lobular and Rare Subtypes of Breast Cancer.

OBJECTIVE: To determine the predictive factors for the pathological complete response (pCR) in patients with non-ductal invasive breast cancer (ND-BC) receiving neoadjuvant chemotherapy. STUDY DESIGN: Observational study. Place and Duration of the Study: Departments of Medical Oncology, Tekirdag Namik Kemal University, Sirnak State Hospital, Aydin Adnan Menderes University, Marmara University, Bakirkoy Sadi Konuk Hospital, Basaksehir Cam and Sakura Hospital, Sakarya University, Balikesir Ataturk Hospital, Turkiye, from April 2016 to December 2022. METHODOLOGY: A total of 222 non-metastatic breast cancer patients who received neoadjuvant chemotherapy were included in this retrospective multicentric study. The clinicopathologic data were obtained from the hospitals' electronic-record-system. The logistic regression models were used to identify predictive factors for pCR. RESULTS: One hundred and twenty-six patients (56.8%) had invasive lobular carcinoma and 28 patients (12.6%) had signet ring cell/mucinous carcinoma. A total of 45 patients (20.3%) achieved pCR. The pCR rate was 14.3% for lobular carcinoma and 17.9% for signet ring cell/mucinous carcinoma. The univariate analysis showed that estrogen receptor-negative tumours (p = 0.017), high Ki-67 (p = 0.008), high histologic grade (p<0.001), HER2+ expression (p<0.001), and non-lobular histologic type (p = 0.012) were predictive factors for pCR. The multivariate model revealed that HER2 expression (p<0.001) and Ki-67 (p = 0.005) were independent predictors. CONCLUSION: Neoadjuvant chemotherapy demonstrated effectiveness in ND-BC patients, leading to favourable pCR rates and enabling breast-conserving surgery. Predictive markers for pCR varied depending on histologic types, with HER2 expression, ER status, Ki-67, and histologic grade showing significance in non-ductal subtypes, while HER2 status alone was predictive in lobular carcinoma. KEY WORDS: Neoadjuvant chemotherapy, Non-ductal breast cancer, Lobular carcinoma.

PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study.

INTRODUCTION: In this study, the toxicities and management of palbociclib and ribociclib in older patients (≥65 years) with metastatic breast cancer patients were investigated. MATERIALS AND METHODS: Among older patients receiving palbociclib and ribociclib, Geriatric 8 (G8) and Groningen Frailty Index were used to evaluate frailty status. Dose modifications, drug withdrawal and other serious adverse events (SAEs) were recorded and analyzed according to baseline patient characteristics. RESULTS: A total of 160 patients from 28 centers in Turkey were included (palbociclib = 76, ribociclib = 84). Forty-three patients were ≥ 75 years of age. The most common cause of first dose modification was neutropenia for both drugs (97% palbociclib, 69% ribociclib). Liver function tests elevation (10%) and renal function impairment (6%) were also causes for ribociclib dose modification. Drug withdrawal rate was 3.9% for palbociclib and 6% for ribociclib. SAEs were seen in 11.8% of those taking palbociclib and 15.5% of those on riboclib. An ECOG performance status of ≥2 and being older than 75 years were associated with dose reductions. Severe neutropenia was more common in patients with non-bone-only metastatic disease, those receiving treatment third-line therapy or higher, coexistance of non-neutropenic hematological side effects (for ribociclib). Neutropenia was less common among patients with obesity. DISCUSSION: Our results show that it can be reasonable to start palbociclib and ribociclib at reduced dose in patients aged ≥75 years and/or with an ECOG performance status ≥2.

Decrease in estimated glomerular filtration rates in non-small cell lung cancer patients treated with crizotinib.

Introduction: Crizotinib is a tyrosine kinase inhibitor used in patients with non-small cell lung cancer, and there are uncertainties about its effect on kidney function. In this study, it was aimed to document the possible adverse effect of the drug on kidney functions. Materials and Methods: The estimated glomerular filtration rates (eGFRs) of the patients were calculated by creatinine-based Chronic Kidney Disease Epidemiology Collaboration and compared by months using the paired samples t-test. Kaplan-Meier survival method was used for progression-free survival and overall survival (OS) analysis. Results: Twenty-six patients who received crizotinib were included in the study, and the median progression-free survival time with crizotinib was 14.2 months and the median OS time was 27.4 months. There was a significant reduction of eGFR after the 1st month of crizotinib treatment when compared to the rate before treatment initiation (P < 0.001). The eGFR values at the end of the 1st month and the 2nd month of treatment and the 2nd and 3rd months of treatment were statistically similar (P = 0.086, P = 0.663; respectively). This decrease in eGFR values was reversible, and there was no difference detected between pretreatment and posttreatment discontinuation (P = 0.100). Conclusion: A reversible decrease in renal functions was detected in patients using crizotinib. When the literature data are examined, it is thought that the reason for this decrease may be related to the increase in renal inflammation or a pseudo decrease due to the decrease in creatinine excretion. When evaluating renal functions in these patients, using noncreatine-based (iothalamate, etc.) calculations can give more accurate results.

Tamoxifen or aromatase inhibitors: which one is the culprit of urinary incontinence in premenopausal breast cancer patients receiving adjuvant hormone therapy?

AIM: The primary aim of this study was to compare tamoxifen versus aromatase inhibitors (AI) in terms of urinary incontinence (UI) in premenopausal female patients receiving adjuvant hormone therapy for breast cancer. A secondary aim was to investigate the prevalence and the affecting factors of UI. METHODS: This study was designed as a multicenter, cross-sectional that included consecutive premenopausal breast cancer patients ≤50 years of age receiving tamoxifen (with/without LHRHa) or AI (with LHRHa) for at least 6 months, between June 2021 and September 2022. Patients with urinary incontinence before hormone treatments and metastatic patients were excluded from the study. Turkish validation of The International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form (ICIQ UI-SF) was used to determine the UI. Using logistic regression methods, we analyzed potential predictive factors for UI. RESULTS: A total of 206 breast cancer patients were included in this study. A total of 120 (58.2%) patients were receiving tamoxifen plus LHRHa, 40 (19.4%) patients were receiving aromatase inhibitor plus LHRHa, and 46 (22.3%) patients were receiving tamoxifen only. In this study, the prevalence of urinary incontinence was found to be 35.9% (n:74). 41% of the patients receiving tamoxifen and 15.0% of those receiving aromatase inhibitors had complaints of urinary incontinence. There was a statistically significant difference between patients receiving tamoxifen or aromatase inhibitor in terms of urinary incontinence (p=0.001). In the univariate analysis established to predict UI, parity (≥2 vs <2) (OR = 3.23, 95% CI: 1.62-6.46, p= 0.001), tamoxifen (vs AI) (OR = 3.97, 95% CI: 1.58-9.98, p= 0.003), age ( ≥40 vs. <40) (OR = 2.80, 95% CI: 1.37-5.71, p= 0.005), vaginal deliveries (≥2 vs. <2) (OR = 3.28, 95% CI: 1.44-7.46, p= 0.005), hypertension (OR = 3.59, 95% CI: 1.43-9.02, p= 0.007), diuretic use (OR = 2.55, 95% CI: 1.09-5.95, p= 0.031) ), and body mass index (≥25 vs <25) (OR = 1.94, 95% CI: 1.05-3.63), p= 0.034) was found to be predictive. Tamoxifen (OR = 4.71, 95% CI: 1.77-12.56, p= 0.002), hypertension (OR = 3.48, 95% CI: 1.27-9.52, p= 0.015), and age (OR = 2.35, 95% CI: 1.10-5.02, p= 0.027) remained independent predictors for incontinence in multivariate analyses. CONCLUSION: We found that tamoxifen had increased the risk of urinary incontinence compared to aromatase inhibitors in patients receiving hormone therapy for breast cancer. In addition, we showed that age and hypertension were also independent predictors for UI. In the context of quality of life, we recommend close follow-up of these patients, as drug adherence may be affected in the event of urinary incontinence.

A New Mortality Prediction Model in Advanced Stage Cancer Patients Requiring Hospitalisation while Receiving Active Systemic Therapy.

OBJECTIVE: To predict short and long-term mortality in patients who were admitted to the emergency department and then hospitalised unplanned in medical oncology-ward. STUDY DESIGN:  An observational study. Place and Duration of the Study: Department of Medical Oncology, Tekirdag Namik Kemal University Hospital, Tekirdag, Turkiye, from May 2021 to May 2022. METHODOLOGY: Consecutive patients admitted to the emergency department with unplanned hospitalisation in the oncology ward, were included. Patients receiving treatment with the curative intent, patients hospitalised for febrile neutropenia, and terminally ill patients requiring intensive care unit follow-up at admission  were  excluded  from  the study.  Univariate  and  multivariate  logistic  regression  analyses were used to identify predictive factors for short and long-term mortality-dependent variables. RESULTS: This study included 253 advanced cancer patients. The number of patients who died in the ward within 10 days (short-term mortality) was 28 (11.1%). Ninety patients (35.6%) died afterwards anytime in the ward during the study (long-term mortality). In the multivariate analysis established for short-term mortality, higher ALT (OR = 6.75, 95% CI: 2.09 - 21.85, p=0.001), rapid deterioration in performance status (OR = 5.49, 95% CI: 1.81-16.67, p=0.003), higher CRP (OR = 5.86, 95% CI: 1.20-28.53, p=0.029), higher procalcitonin (OR = 7.94, 95% CI: 0.99 - 63.82, p=0.051), and higher lactate (OR = 2.47, 95% CI: 0.94-6.51, p=0.067) showed significant predictive features. CONCLUSION: The decision of whether to continue treatment or not is challenging in cancer patients who require unplanned hospitalisation while receiving palliative systemic therapy. New mortality estimation models can be used in making the transition from life-long to palliative treatments. KEY WORD: Mortality prediction, Hospitalisation, Estimation of survival, Chemotherapy.

A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy.

OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034). CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.

Oxidase mimicking Co/2Fe MOF included biosensor for sialic acid detection.

A facile amperometric biosensor that included oxidase mimicking Co/2Fe metal-organic framework (MOF) for sialic acid (SA) detection was prepared. Amperometric SA biosensor was constructed on a gold screen-printed electrode via immobilization of Co/2Fe MOF and N-acetylneuraminic Acid Aldolase (NANA-Aldolase) enzyme, respectively. NANA-Aldolase enzyme converts free SA into pyruvate and N-acetyl-d-mannosamine. After this conversion, oxidase mimicking Co/2Fe bimetallic MOF converts pyruvate into acetylphosphate and O2 into H2O2. Investigation of analytical characteristics resulted with the linear range of 0.02 mM-1.00 mM of SA concentration with limit of detection value of 0.026 mM. Sample application studies with developed SA biosensor were carried out with GD3 ganglioside and HeLa cancer cell lines which have high SA concentrations while A549 cell lines were also used as control group. Before detecting free SA, the bound SA was freed from SA sources where every step was monitored via electron impedance spectroscopy. Then, free SA was successfully detected with the amperometric SA biosensor and as a result, more practical and accurate system was developed.

Comprehensive Analysis of Prognostic Factors in Advanced Gastric Cancer Patients Treated with Chemotherapy.

OBJECTIVE: To evaluate the strongest prognostic factors in advanced gastric cancer. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Tekirdag Namik Kemal University, Tekirdag, Turkey, between March 2012 and April 2022. METHODOLOGY: Adult patients with metastatic cancer who had completed at least two months of chemotherapy, without any other comorbidity were included. Using Kaplan-Meier methodology and Cox regression methods, potential prognostic factors were analysed for overall survival. Two different models were created for multivariate analysis by using statistically significant factors in univariate analysis. RESULTS: The median overall survival in 216 patients was 7.8 months. The univariate analysis showed that body-mass index, performance status, liver metastasis, albumin, gamma-glutamyl transferase, carcinoembryonic antigen, carbohydrate antigen (CA 19-9), neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index, albumin-to-alkaline phosphatase ratio, sodium-globulin ratio (SGR) prognostic nutritional index (PNI), albumin-bilirubin ratio, and albumin-globulin ratio were associated with survival. In Model 1, which included only laboratory indices, multivariate analyses revealed that NLR (p=0.001), SGR (p=0.025), and PNI (p=0.032) were prognostic for overall survival. In Model 2, established with all parameters, NLR (p=0.003), albumin (p=0.003), performance status (p<0.001), and CA 19-9 (p<0.001) were found to be independent prognostic factors. CONCLUSION: Pretreatment NLR, SGR, PNI, albumin, performance status, and CA 19-9 are strong prognostic factors in patients with advanced gastric cancer. These prognostic factors, which are easily accessible in clinical practice, may be utilised as useful tools for clinicians. KEY WORDS: Gastric cancer, Prognosis, Overall survival, Chemotherapy, Metastasis, Prognostic biomarkers.

Efficacy and safety of trastuzumab emtansine treatment in patients with metastatic HER-2 positive breast cancer: a single center study / Eficacia y seguridad del tratamiento con trastuzumab emtansina en pacientes con cáncer de mama metastásico HER-2 positivo: estudio de un solo centro

Introduction: Trastuzumab emtansine (T-DM1) is one of the effective treatment options in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. In this study, we aimed to find the effect of T-DM1 on survival, its tolerability and prognostic factors of T-DM1 treatment. Material and methods: The study was designed as a single-center, retrospective study that included patients treated in the oncology department of a university hospital in Turkey. HER2-positive patients with metastatic breast cancer who had a progression response to trastuzumab and taxane treatment and received T-DM1 treatment for at least 2 months between 2016-2022 were included in the study. Adverse events were defined according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE). Kaplan-Meier methodology and Cox proportional hazard modelling were used for survival analyses. Results: The median progression-free survival (mPFS) for T-DM1 was 10.4 months and the median overall survival (mOS) was 22 months. In the created univariate cox regression model, liver metastasis, ECOG performance status, and pre-treatment serum CA 15-3 were found to be factors associated with PFS. Liver metastasis (HR=2.54, p=0.019), ECOG performance status (HR=4.66, p=0.002), and serum CA 15-3 (HR= 2.55, p=0.041) maintained their statistical significance for PFS in the established multivariate analysis. In the regression analysis for OS, only ECOG performance status (HR= 2.61, p=0.023) was found to be prognostic. While toxicity occurred in 46 (82.1%) of the patients, grade 3-4 toxicity developed in 10 (17.9%) patients. The most common side effects were anemia, thrombocytopenia, fatigue and nausea. Conclusions: T-DM1 is a safe and tolerable agent that prolongs survival. Liver metastasis, ECOG performance status, and pre-treatment serum CA 15-3 levels are independent prognostic factors for patients using T-DM1. (AU)

Introducción: Trastuzumab emtansina (T-DM1) es una de las opciones de tratamiento eficaces en pacientes con cáncer de mama positivo para el receptor 2 del factor de crecimiento epidérmico humano (HER2). En este estudio, nuestro objetivo fue encontrar el efecto de T-DM1 en la supervivencia, su tolerabilidad y los factores pronósticos del tratamiento con T-DM1. Material y métodos: El estudio se diseñó como un estudio retrospectivo unicéntrico que incluyó pacientes tratados en el departamento de oncología de un hospital universitario en Turquía. Se incluyeron en el estudio pacientes HER2 positivas con cáncer de mama metastásico que tuvieron una respuesta progresiva al tratamiento con trastuzumab y taxanos y recibieron tratamiento con T-DM1 durante al menos 2 meses entre 2016 y 2022. Los eventos adversos se definieron de acuerdo con los Criterios de Terminología Común para Eventos Adversos v5.0 (CTCAE). Se utilizaron la metodología de Kaplan-Meier y el modelo de riesgos proporcionales de Cox para los análisis de supervivencia. Resultados: La mediana de supervivencia libre de progresión (mPFS) para T-DM1 fue de 10,4 meses y la mediana de supervivencia general (mOS) fue de 22 meses. En el modelo de regresión de cox univariable creado, se encontró que la metástasis hepática, el estado funcional ECOG y el CA 15-3 sérico previo al tratamiento son factores asociados con la SLP. La metástasis hepática (HR = 2,54, p = 0,019), el estado funcional ECOG (HR = 4,66, p = 0,002) y el suero CA 15-3 (HR = 2,55, p = 0,041) mantuvieron su significación estadística para la SLP en el estudio multivariable establecido. análisis. En el análisis de regresión para OS, solo se encontró que el estado funcional ECOG (HR= 2.61, p=0.023) era pronóstico. Si bien se produjo toxicidad en 46 (82,1 %) de los pacientes, se desarrolló toxicidad de grado 3-4 en 10 (17,9 %) pacientes. Los efectos secundarios más comunes fueron anemia, trombocitopenia, fatiga y náuseas. Conclusiones: . ... . (AU)

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

Soluble B7H3 level in breast cancer and its relationship with clinicopathological variables and T cell infiltration.

Aim of the study: Although early diagnosis of breast cancer (BC) is often associated with a good prognosis, there is currently no biomarker with high sensitivity serving this purpose. B7H3, a recently identified member of the B7 family, appears to inhibit antitumor immunity. We investigated the soluble B7H3 (sB7H3) level in BC and its relationship with clinicopathological variables and stromal tumor-infiltrating lymphocytes (sTILs). Material and methods: The study, which was designed as a cross-sectional trial between January 2020 and September 2021, included 93 BC patients, 20 patients with benign breast disease (BBD) and 14 healthy volunteers as the control group. Serum sB7H3 levels were measured using the ELISA (enzyme-linked immunosorbent assay) method and sTILs were measured by immunohistochemistry using Tru-cut biopsy materials. Results: sB7H3 levels in BC patients were significantly higher than those in patients with BBD and healthy volunteers. Receiver operating characteristic curve analysis results showed that sB7H3 level may be a potential biomarker for distinguishing patients with BC from those with BBD (AUC: 0.807; sensitivity: 0.786; specificity: 0.706) and from healthy volunteers (AUC: 0.731; sensitivity: 0.700; specificity: 0.692). Conclusions: To the best of our knowledge, the present study is the first to investigate the relationship between sB7H3 and disease parameters in BC. We found that sB7H3 may be a clinically practical and meaningful biomarker in differentiating BC from BBD. In order to evaluate the relationship of B7H3 with clinical variables in BC, and especially with sTILs, tissue-based studies with higher numbers of patients are needed.

Immunogenicity and safety of the CoronaVac vaccine in patients undergoing treatment for breast and lung cancer.

OBJECTIVE: To compare seroconversion for SARS-CoV-2 receptor-binding domain (RBD) specific IgG positivity against two doses of the CoronaVac vaccine in breast and lung cancer patients receiving systemic therapy, to determine the factors affecting seropositivity, and to observe long-term results up to a secondary booster vaccine. RESULTS: The analysis included 201 cancer patients (99 breasts, 102 lungs; median age: 59 years (range: 28-92), 42.3 % men) and 97 controls (median age: 62 years (range: 24-87), 38.1 % men). The seropositivity rate for RBD IgG after 2 doses of vaccine in the cancer group was 81.6 % (n=164) and 93.8 % (n=91) in the control group (p=0.005). The median IgG titer of cancer patients was significantly lower than in the control group (338 (IQR, 95-933) AU/mL vs 676 (IQR, 389-1270) AU/mL; p<0.001). Multivariate analysis of all the patients determined that having cancer (OR: 0.303, 95%CI: 0.123-0.750, p=0.010) and being over 60 years of age (OR: 0.447, 95%CI: 0.218-0.917, p=0.028) was associated with a reduced vaccine response. A subgroup analysis of cancer patients revealed that seroconversion was lower in men than in women (75.3 % vs 86.2 %, p=0.049) and lower in ≥60 patients than in <60 patients (75.9 % vs 89.4 %, p=0.014). DISCUSSION AND CONCLUSION: Cancer patients receiving an active systemic therapy with two doses of the CoronaVac vaccine had a lower antibody response than the non-cancer population, and deaths due to COVID-19 may occur in these patients despite the vaccine. Therefore, extensive protective measures should be taken to protect against COVID-19 in cancer patients aged 60 years and older, who have received two doses of the CoronaVac vaccine (Tab. 4, Fig. 4, Ref. 27).

Prospective comparison of the value of CARG, G8, and VES-13 toxicity tools in predicting chemotherapy-related toxicity in older Turkish patients with cancer.

BACKGROUND: In older patients with cancer, it is very important to choose the appropriate treatment because they are at high risk for chemotherapy toxicity. Our study investigated characteristics of Cancer and Aging Research Group (CARG), Geriatric 8 (G8), and Vulnerable Elders Survey (VES-13) screening tools for predicting chemotherapy-related toxicity (CRT) prospectively. MATERIALS AND METHODS: 208 patients aged ≥65 years old for whom chemotherapy was planned to treat non-haematological cancer between February 2021-September 2021 were included in the study. The CARG, G8, and VES-13 toxicity tools were completed by the oncologist through face-to-face interviews before starting the first chemotherapy treatment. CRTs during chemotherapy were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03. Logistic regression models, the area under the receiver operating characteristic curve (ROC-AUC), and correlation analyses were used for comparing questionnaires. RESULTS: Median age was 70.4 (range 65-86) years. Of the participants, 103 (49.5%) participants experienced grade 3-5 CRT (32.2% haematological, 28.4% non-haematological) during chemotherapy. ROC-AUC value of CARG was determined as 0.827 (95% CI [confidence interval]: 0.77-0.88, p < 0.001), it was determined as 0.744 (95% CI: 0.68-0.81, p < 0.001) for G8 and 0.726 (95% CI: 0.66-0.80, p < 0.001) for VES-13. In the univariate regression analysis, CARG (OR [odds ratio] = 13.57, 95% CI: 6.0-30.72, p < 0.001), G8 (OR = 3.19, 95% CI: 1.62-6.29, p = 0.001), and VES-13 (OR = 9.5, 95% CI: 5.01-17.89, p < 0.001) were found to be predictive for CRT. The multivariate analysis (included stage, Eastern Cooperative Oncology Group [ECOG] performance status, presence of comorbid disease, platinum-based treatment regimen, taxane-based treatment regimen, CARG, VES-13, G8) showed that CARG (OR = 12.08, 95% CI: 5.11-28.56, p < 0.001), VES-13 (OR = 10.06, 95% CI: 4.92-22.98, p < 0.001), and G8 (OR = 2.20, 95% CI: 1.04-4.69, p = 0.040) screening tools were strong predictors for CRT. The CARG and VES-13 questionnaires were predictive for reducing the initial treatment dose (p = 0.004, p = 0.004, respectively), interruption of treatment (p < 0.001, p < 0.001, respectively), discontinuing treatment (p = 0.002, p = 0.002, respectively), and unexpected hospitalisation (p = 0.012, p = 0.003, respectively). CONCLUSIONS: We showed that all three CARG, G8, and VES-13 questionnaires are helpful tools in the decision-making process for ideal chemotherapy to predict severe CRT; however, CARG and VES-13 questionnaires appear more useful in daily oncology practice than the G8 questionnaire.

The diagnostic contribution of magnetic resonance imaging in the detection of axillary metastasis after neoadjuvant chemotherapy.

Sentinel lymph node dissection (SLND) is a reliable method that provides axillary staging in clinical node-negative (cN0) breast cancer patients before neoadjuvant chemotherapy (NACT). However, it is not a standard method on its own due to the high false-negative rates (FNR) reported in initially clinical node-positive patients (cN1-cN3). The contribution of magnetic resonance imaging (MRI) to SLND after chemotherapy is not well understood. In our study, we aimed to investigate the contribution of post-NACT MRI to SLND in breast cancer patients receiving NACT. Between January 2014 and December 2020, patients who had MRI images including the axilla after NACT and had axillary lymph nodes evaluation performed simultaneously with SLND were included in the study. MRI images of all patients were re-evaluated by 2 experienced clinicians. MRI and SLND results were analyzed to detect axillary lymph node metastasis. 117 patients were included in the study. The median age of the patients was 49 years. Before chemotherapy, 108 patients (92.3%) had tumor metastases in their axilla pathologically confirmed by tru-cut biopsy. Axillary downstage was obtained in 48.1% (n=52) of the patients after NACT. Of the 56 patients with axillary node positivity, 3 patients had no metastasis in the SLND evaluation (FNR=5.4%). The sensitivity of post-NACT MRI in detecting node positivity was 69.6%, the specificity was 90.2%, the positive predictive value (PPV) was 86.7% and the negative predictive value (NPV) was 76.4. SLND together with MRI predicted all node-positive patients (FNR=0%). In summary, SLND may not detect a group of patients with residual axillary lymph node metastases after NACT. We have shown that MRI can contribute to identifying these patients. If no metastases are detected by both methods (SLND and MRI), avoidance of axillary dissection may be an acceptable choice.

The influence of visual objects and music on anxiety levels of breast cancer patients scheduled to experience chemotherapy for the first time: a prospective randomized clinical study.

OBJECTIVE: To investigate the influence of music together with visual objects as an ambiance in the waiting room on anxiety levels of breast cancer patients scheduled to receive chemotherapy in outpatient setting for the first time. MATERIAL AND METHOD: Breast cancer patients planned to receive adjuvant or neoadjuvant chemotherapy for the first time between November 1, 2020, and July 31, 2021, were included. Two designs, including a standard waiting room (StWR) and an intervention waiting room (IWR) that was created by adding music and visual objects to the standard room, were constructed. These 2 designs were repeated sequentially in monthly periods, and a total of 104 patients with 52 in each group were randomized. The State Trait Anxiety Inventory (STAI) and Hospital Anxiety and Depression Scale (HADs) were used for assessments. Results of the patients in StWR and IWR groups were compared. RESULTS: Both HADs anxiety and STAI-state anxiety scale scores were lower in patients who waited in IWR compared to those who waited in StWR (p = 0.041, p = 0.012, respectively). In patients in the IWR group, mean heart rate was lower by 7.6 bpm (p = 0.009). No difference was found between the groups with regard to HADs depression score and STAI-trait anxiety score (p = 0.305, p = 0.535, respectively). For all patients, HADs anxiety scale (r = 0.400, p = < 0.001) and STAI-state anxiety scale (r = 0.475, p = < 0.001) scores increased as the waiting time increased. DISCUSSION AND CONCLUSION: The present study is the first to investigate the influence of adding music together with visual objects to the standard ambiance of the chemotherapy waiting room on anxiety levels of breast cancer patients. We propose that introduction of paintings, artificial plants, and music to the ambiance of the waiting room has a significantly positive effect on alleviating anxiety levels of cancer patients waiting for chemotherapy.

Efficacy and safety of trastuzumab emtansine in older patients with HER2-positive advanced breast cancer: a real-world study.

INTRODUCTION: Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate and its survival advantage has been shown in advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, clinical trials underrepresent patients ⩾65 years of age, leading to a lack of information in this population. We analyzed the real-world outcomes of older women who were treated with T-DM1 therapy. METHODS: We performed a multicenter, observational, retrospective analysis of patients aged ⩾65 years treated with T-DM1. A total of 93 patients from 10 cancer centers were involved in the study. Our goal was to determine the survival, response rates, and toxicity profile in T-DM1-treated patients, as well as the factors that influence survival. RESULTS: Median follow-up was 12.2 months. Objective response rate was 29%. Median progression-free survival (PFS) and overall survival (OS) were 8.47 and 15.0 months, respectively. In multivariate analysis, Eastern Cooperative Oncology Group Performance Score 2 was found to be an independent prognostic factor for worse PFS (hazard ratio [HR] 1.81, p = 0.032) and OS (HR 2.33, p = 0.006). Any adverse event (AE) was seen in 92.5% of patients; grade 3 or 4 AEs were seen in 30.1%. Dose reduction or treatment discontinuation rates were 11.8% and 6.5%, respectively. CONCLUSION: The efficacy of T-DM1 was acceptable and it was generally well-tolerated among older patients with advanced HER2-positive breast cancer.

Breast cancer in young and very young women; Is age related to outcome?

BACKGROUND: Breast cancer in young women is associated with aggressive biology. We analyzed histopathological and clinical properties of breast cancer patients diagnosed at ≤40 years of age. METHODS: Breast cancer patients who were admitted between 2015 and 2019 were included. Baseline characteristics of the patients with treatment-related outcomes were assessed. The study group was divided into two subgroups; <35 years old as "very young" and ≥35 years old as "young." RESULTS: The data of 137 patients (60 patients <35 years) were reviewed. The mean age was 34.7 years. The mean follow-up duration was 44.45 ± 26.39 months, and the mean disease-free survival was 36.17 ± 21.97 months. 11.4% of the patients were diagnosed with Stage 4 disease. Pathologic subtype was invasive ductal carcinoma in 86% of patients. 16.8% of the patients were luminal A, 38.7% luminal B, 30.5% were human epidermal growth factor receptor-2-positive type, and 15.3% were triple-negative. Only 5 (3.3%) patients had given birth after chemotherapy. During the follow-up period of early-staged diagnosed patients, metastatic disease occurred in 24.6%. The rate of distant metastasis development was statistically higher in the very young group (31% vs. 11%; P = 0.004). Thirteen patients (10.7%) died due to disease progression. Thirty-seven percent of the patients had a positive family history for either breast or ovarian cancer. CONCLUSIONS: Very young breast cancer patients seem to have a more aggressive disease course. The low rate of childbearing in this young patient population is conspicuous. An interdisciplinary approach for the management of this special patient population should be taken into consideration.

Mindfulness Among Medical Oncology Doctors and Its Relation With Burnout: Turkish Oncology Group (TOG) Study.

PURPOSE: Medical oncology physicians have been identified as one of the main risk groups for the development of burnout. Mindfulness as being aware of the moment nonjudgmentally seems to be a protective factor against burnout. We aimed to reveal mindfulness levels among medical oncology doctors and the potential impact of mindfulness on burnout syndrome. METHODS: In this cross-sectional study, the data of 285 medical oncology doctors were analyzed. The Mindful Attention Awareness Scale was used for mindfulness evaluation, and the Maslach Burnout Inventory was used for burnout assessment. After defining mindfulness levels among medical oncology doctors, the relationship between mindfulness and burnout was analyzed by the Pearson correlation and bivariate logistic regression tests. RESULTS: The mean Mindful Attention Awareness Scale score of participants was 54.52 ± 13.77. Mindfulness was associated with age (P < .001), having a hobby (P = .008), regular exercise (P = .001), professional title (P = .02), and professional experience (P = .02). As the level of mindfulness increased, emotional exhaustion and depersonalization decreased, whereas personal accomplishment increased significantly (all P < .001). In the regression analysis, mindfulness was significantly associated with all three subscales of burnout (all P < .01). CONCLUSION: We have demonstrated for the first time on such a large scale that higher levels of mindfulness were related with lower burnout among medical oncology physicians. These findings suggest the potential benefits of mindfulness-based interventions in reducing burnout levels in medical oncologists.