Sensitivity of frozen section analysis in patients with ovarian adult granulosa cell tumor, a multi-center study.

INTRODUCTION: We aimed to demonstrate the sensitivity of frozen section for patients with adult granulosa cell tumor (AGCT) and analyze the clinico-pathological factors that may be associated with sensitivity. MATERIAL METHODS: This is a multicenter study including data of 10 Gynecological Oncology Departments. Frozen-section results of patients who had ovarian AGCT at the final pathology report were retrospectively analyzed. The relation between clinico-pathological characteristics such as age, tumor size, Ca-125 level, presence of ascites, omental metastasis, menopausal status and peritoneal cytology, and the sensitivity of frozen section in patients with AGCT were evaluated. The sensitivity of frozen section diagnosis was determined by comparing the frozen section result with the final pathological diagnosis. RESULTS: Frozen section results of 274 patients with AGCT were obtained. The median age of the patients was 52 years (range, 17-82 years). Totally, 144 (52.7%, n = 273) patients were postmenopausal. The median tumour size was 90 mm (range, 9-700 mm). The median preoperative Ca-125 level was 23 IU/mL (range, 2-995 IU/mL). The sensitivity of frozen section for detecting AGCT was 76.3%. Any association between the sensitivity of frozen section and menopausal status, presence of ascites, positive cytology, omental metastasis, tumor size, Ca-125 level, age could not be shown. CONCLUSION: It is important to know the diagnosis of AGCT intraoperatively, and we demonstrated the sensitivity of frozen-section for these tumors as 76.3%.

Efficacy and safety of G-CSF prophylaxis in patients with extensive-stage small cell lung cancer receiving chemoimmunotherapy.

OBJECTIVES: We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC). METHODS: This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. RESULTS: Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group (p = 0.33), and the DCR was 85.4% versus 70.0%, respectively (p = 0.46). Median PFS was 8.3 months (95% CI, 6.8-9.8) in the G-CSF group and 6.8 months (95% CI, 6.2-7.5) in the non-G-CSF group (p = 0.24). Median OS was 13.8 months (95% CI, 9.6-18.1) for the G-CSF group and 10.6 months (95% CI, 7.9-13.3) for the non-G-CSF group (p = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p = 0.12). CONCLUSION: G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.

The Comparison of FLOT and DCF Regimens as Perioperative Treatment for Gastric Cancer.

INTRODUCTION: Locoregional gastric cancer is a still serious problem and perioperative treatments may improve the success of management. Different regimens were examined. The present study purposed to compare the efficacy of fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) and docetaxel-cisplatin-fluorouracil (DCF) regimens. METHODS: A retrospective multicenter study assessed the patients with locoregional gastric cancer. There are 240 patients (137 DCF, 103 FLOT). Survival rates were compared. RESULTS: Demographic features were similar between the two groups, but the time period was different. The FLOT group had 7.8% pathological complete response, while the DCF group did not. Disease-free survival was longer in the FLOT than in the DCF group (median not reached - 13.94 months, respectively). Median overall survival was similar (30.9 vs. 37.8 months), but median follow-up affected the analysis. Survival for 36 months was 63% for the FLOT group and 40% for the DCF group (log-rank; p = 0.015). CONCLUSION: FLOT regimen was superior to DCF regimen for response and survival rates. DCF is a historical approach. Long-term follow-up period is needed for FLOT treatment.

Efficacy of cumulative cisplatin dose on survival in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy: multicenter study by Turkish Oncology Group.

OBJECTIVE: To investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy. METHODS: A retrospective analysis was conducted on 654 patients with stage IB3-IVA disease treated with definitive chemoradiotherapy. Radiotherapy was applied as external beam pelvic with or without para-aortic radiotherapy and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3 weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were used to assess factors influencing progression free survival and overall survival. RESULTS: The median cumulative cisplatin dose was 210 mg (range 40-320), and ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months (range 1-150). The 5 year progression free survival and overall survival rates were 66.9% and 77.1%, respectively. Multivariate analysis identified poor performance status, non-squamous cell histology, presence of lymph node metastases, and hemoglobin <10 g/dL before chemoradiotherapy as poor prognostic factors for both progression free survival and overall survival in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose <200 mg was found to be a significant poor prognostic factor in overall survival (hazard ratio 1.79, 95% confidence interval 1.1 to 3.0, p=0.031). CONCLUSION: Our study showed that a cumulative cisplatin dose >200 mg, particularly in patients with lymph node metastases, significantly improved overall survival. Factors such as anemia, toxicity related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer.

Does neoadjuvant chemotherapy reduce surgical complexity in patients with advanced-stage epithelial ovarian cancer?

BACKGROUND: This study aimed to determine the effect of neoadjuvant chemotherapy (NACT) on the complex surgical procedures required in addition to staging surgery for the need to achieve a residual tumor 1 cm or less in a population of stage IIIC-IV epithelial ovarian cancer patients. METHODS: Patients were referred for NACT if preoperative imaging and/or intraoperative evaluation confirmed that it was not possible to achieve a residual tumor size of 1 cm or less with cytoreductive surgery or if the patient had a poor performance status and a high American Society of Anesthesiologists (ASA) score. Surgical complexity was defined as complex or non-complex. RESULTS: One hundred and twenty-six patients with stage IIIC-IV ovarian cancer were included in the study. Primary cytoreductive surgery was performed in 67 patients, and interval cytoreductive surgery was performed in 59 patients after NACT. At least one complex surgery was performed in 74.6% of the patients in the primary cytoreductive surgery group and in 61% of the patients in the NACT group, with no statistically significant difference between the groups. However, the NACT group showed significantly decreased rates of low-rectal resection, diaphragmatic peritoneal stripping, and peritonectomy. CONCLUSIONS: The analyses showed no reduction in the requirement for at least one complex surgical procedure in the group of patients who underwent NACT. Nevertheless, this group exhibited a significant decrease in low-rectal resection, diaphragmatic peritoneal stripping, and peritonectomy due to their effectiveness in reducing peritoneal disease.

Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG).

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. MATERIALS AND METHODS: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. RESULTS: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. CONCLUSION: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

Effect of HER2/CEP17 ratio on survival in metastatic HER2-positive gastric cancer, multicenter study.

AIM: HER2-positive metastatic gastric cancer is still a highly fatal disease despite advances. We aimed to investigate the relationship between HER2/CEP17 ratio and survival in patients with HER2-positive metastatic gastric cancer. METHODS: A total of 99 patients from 8 different centers in Turkey were included in the study. Patients with HER2-positive metastatic gastric cancer and whose HER2/CEP17 ratio was examined were included in the study. Patients were divided into two groups according to HER2/CEP17 values, and survival analysis was performed. RESULTS: The median age was 64 (24-83) years. There were 74 (74.8%) male and 25 (25.2%) female patients. OS in the high HER2/CEP17 ratio group was 21.97 months (95% CI: 16.36-27.58), and in the low ratio group was 16.17 months (95% CI: 10.95-21.38) (p = 0.015). OS was 17.7 months (95% CI: 7.02-28.37) in the high HER2 gene copy number group and 10.13 months (5.55-14.71) in the group with low copy number (p = 0.03). PFS was 10.94 months (95% CI: 7.55-14.33) in the group with high HER2 gene copy number and 7.56 months (4.62-10.49) in the low copy number group (p = 0.06). CONCLUSION: Patients with both high HER2 gene amplification and high HER2/CEP17 ratio had better OS. The PFS of the group with high HER2 gene amplification was also better. To our knowledge, this is the first study in the literature showing that the HER2/CEP17 ratio affects survival in patients with metastatic gastric cancer.

Retrospective Analyses of PD-L1, LAG-3, TIM-3, OX40L Expressions and MSI Status in Gastroenteropancreatic Neuroendocrine Neoplasms.

We investigated expressions of PD-L1, LAG-3, TIM-3, and OX40L as immune checkpoint proteins, and MSI (repetitive short-DNA-sequences due to defective DNA-repair system) status were analyzed with immunohistochemistry from tissue blocks. Of 83 patients, PD-L1 expression was observed in 18.1% (n = 15) of the patients. None of the patients exhibited LAG-3 expression. TIM-3 expression was 4.9% (n = 4), OX40L was 22.9% (n = 19), and 8.4% (n = 7) of the patients had MSI tumor. A low-to-intermediate positive correlation was observed between PD-L1 and TIM-3 expressions (rho: 0.333, p < 0.01). Although PD-L1 expression was higher in grade 3 NET/NEC, MSI status was prominent in grade 1/2 NET.

Defining the relationship between ovarian adult granulosa cell tumors and synchronous endometrial pathology: Does ovarian tumor size correlate with endometrial cancer?

OBJECTIVE: The main feature of adult granulosa cell tumors (AGCT) is their capacity to secrete hormones, with nearly all of them capable of synthesizing oestradiol. The primary goal of this study is to identify synchronized endometrial pathologies, particularly endometrial cancer, in AGCT patients who had undergone a hysterectomy. MATERIALS AND METHODS: The study cohort comprised retrospectively of 316 AGCT patients from 10 tertiary gynecological oncology centers. AGCT surgery consisted of bilateral salpingo-oophorectomy, hysterectomy, peritoneal cytology, omentectomy, and the excision of any suspicious lesion. The median tumor size value was used to define the relationship between tumor size and endometrial cancer. The relationship between each value and endometrial cancer was evaluated. RESULTS: Endometrial intraepithelial neoplasia, or hyperplasia with complex atypia, was detected in 7.3% of patients, and endometrial cancer in 3.1% of patients. Age, menopausal status, tumor size, International Federation of Gynecology and Obstetrics stage, ascites, and CA-125 level were not statistically significant factors to predict endometrial cancer. There was no endometrial cancer under the age of 40, and 97.8% of women diagnosed with endometrial hyperplasia were over the age of 40. During the menopausal period, the endometrial cancer risk was 4.5%. Developing endometrial cancer increased to 12.1% from 3.2% when the size of the tumor was >150 mm in menopausal patients (p = 0.036). CONCLUSION: Endometrial hyperplasia, or cancer, occurs in approximately 30% of AGCT patients. Patients diagnosed with AGCT, especially those older than 40 years, should be evaluated for endometrial pathologies. There may be a relationship between tumor size and endometrial cancer, especially in menopausal patients.

Cabozantinib-induced heart failure.

INTRODUCTION: Cabozantinib is a multikinase inhibitor agent used in the treatment of hepatocellular, renal, and thyroid cancers. The development of heart failure after cabozantinib initiation is an extremely rare side effect, with only four case reports published in the literature. We describe a case of cabozantinib-induced cardiac failure in a patient with thyroid cancer refractory to standard treatment. CASE REPORT: Fifty-seven-year-old woman had no history of cardiovascular disease. Echocardiography prior to chemotherapy revealed normal cardiac function. However, she developed pretibial edema and shortness of breath after 2 months of cabozantinib treatment. Ejection fraction was found to be 30% in the echocardiography of the patient, and global hypokinesia was detected in cardiac functions. MANAGEMENT AND OUTCOME: Cabozantinib treatment of the patient was discontinued. After discontinuation of treatment, the patient's cardiac functions did not return to normal. Heart failure due to cabozantinib treatment was thought to be permanent. DISCUSSION: There are only four cases on this subject in the literature. Although the use of cabozantinib rarely causes heart failure, this side effect can have extremely serious consequences. Even if it is a rare condition, cardiological evaluations should be performed before and after cabozantinib therapy because it can be reversible after discontinuation of the treatment.

Is adjuvant chemotherapy necessary for 2014 FIGO stage IC adult granulosa cell tumor?: Multicentric Turkish study.

AIM: The aim of our study is to examine the clinical, surgical, and pathological factors of stage 1C adult granulosa cell tumor (AGCT) patients and to investigate the effects of adjuvant therapy on recurrence and survival rates in this patient group. METHODS: Out of a total of 415 AGCT patients treated by 10 tertiary oncology centers participating in the study, 63 (15.2%) patients with 2014 FIGO stage IC constituted the study group. The FIGO 2014 system was used for staging. Patient group who received adjuvant chemotherapy was compared with patient group who did not receive adjuvant chemotherapy in terms of disease-free survival (DFS), and disease-specific survival. RESULTS: The 5-year DFS of the study cohort was 89%, and the 10-year DFS was 85%. Those who received adjuvant chemotherapy and those who did not were similar in terms of clinical, surgical and pathological factors, except for peritoneal cytology. In the univariate analysis, none of the clinical, surgical or pathological factors were significant for DFS. Adjuvant chemotherapy and type of treatment protocol had no impact on DFS. CONCLUSION: Adjuvant chemotherapy was not associated with improved DFS and overall survival in stage IC AGCT. Multicentric and randomized controlled studies are needed for early stage AGCT in order to confirm these results and reach accurate conclusions.

Prognostic factors of adult granulosa cell tumors of the ovary: a Turkish retrospective multicenter study.

OBJECTIVE: To define the clinical, histopathological features and the prognostic factors affecting survival in patients with adult granulosa cell tumors of the ovary (AGCT). METHODS: A 322 patients whose final pathologic outcome was AGCT treated at nine tertiary oncology centers between 1988 and 2021 participated in the study. RESULTS: The mean age of the patients was 51.3±11.8 years and ranged from 21 to 82 years. According to the International Federation of Gynecology and Obstetrics 2014, 250 (77.6%) patients were stage I, 24 (7.5%) patients were stage II, 20 (6.2%) patients were stage III, and 3 (7.8%) were stage IV. Lymphadenectomy was added to the surgical procedure in 210 (65.2%) patients. Lymph node involvement was noted in seven (3.3%) patients. Peritoneal cytology was positive in 19 (5.9%) patients, and 13 (4%) had metastases in the omentum. Of 285 patients who underwent hysterectomy, 19 (6.7%) had complex hyperplasia with atypia/endometrial intraepithelial neoplasia, and 8 (2.8%) had grade 1 endometrioid endometrial carcinoma. It was found that 93 (28.9%) patients in the study group received adjuvant treatment. Bleomycin, etoposide, cisplatin was the most commonly used chemotherapy protocol. The median follow-up time of the study group was 41 months (range, 1-276 months). It was noted that 34 (10.6%) patients relapsed during this period, and 9 (2.8%) patients died because of the disease. The entire cohort had a 5-year disease-free survival (DFS) of 86% and a 5-year disease-specific survival of 98%. Recurrences were observed only in the pelvis in 13 patients and the extra-abdominal region in 7 patients. The recurrence rate increased 6.168-fold in patients with positive peritoneal cytology (95% confidence interval [CI]=1.914-19.878; p=0.002), 3.755-fold in stage II-IV (95% CI=1.275-11.063; p=0.016), and 2.517-fold in postmenopausal women (95% CI=1.017-6.233; p=0.046) increased. CONCLUSION: In this study, lymph node involvement was detected in 3.3% of patients with AGCT. Therefore, it was concluded that lymphadenectomy can be avoided in primary surgical treatment. Positive peritoneal cytology, stage, and menopausal status were independent prognostic predictors of DFS.

Retrospective Evaluation of the Efficacy of Gemcitabine-Based Therapies After FOLFIRINOX Failure in Advanced Pancreatic Cancer, Multi-Center Real-Life Data.

OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.

Efficacy of adjuvant CDK4/6 inhibitors in hormone receptor-positive breast cancer: a systematic review and meta-analysis.

BACKGROUND: The combination of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and standard endocrine therapy (ET) in the adjuvant treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) has yielded conflicting results. We performed a pooled analysis of the adjuvant efficacy of CDK4/6 inhibitors by including data from the NATALEE trial, the most recent trial on this topic. METHODS: We searched major databases and congress proceedings until 7 June 2023 to identify randomized controlled trials (RCT) comparing adjuvant CDK4/6 inhibitor plus ET combination versus ET in HR-positive/HER2-negative early-stage BC. RESULTS: Four RCTs involving a total of 17,749 patients were included. According to the pooled analysis of these four studies, significant improvement in invasive disease-free survival (iDFS) was observed with the addition of CDK4/6 inhibitors to standard ET (HzR: 0.81, 95% CI 0.67-0.97). IDFS benefit was irrespective from menopausal status, Ki-67 index, tumor grade, and previous chemotherapy. CDK4/6 inhibitors plus ET had a significant improvement in iDFS in stage 3 whereas there was a trend toward better iDFS in stage 2 (HzR for stage 3: 0.67, 95% CI 0.58-0.78; HzR for stage 2: 0.74, 95% CI 0.55-1.01). CONCLUSIONS: Addition of CDK4/6 inhibitors to standard ET in the adjuvant treatment of HR-positive/HER2-negative early-stage BC improves iDFS.

The Prognostic and Functional Impact of Sprouty 2 Expression in Non-small Cell Lung Cancer.

OBJECTIVE: We represent Sprouty 2 (Spry2) expression analysis and its association with key driver mutations and clinical features of patients with non-small cell lung cancer as the largest ex vivo data. METHODS: The strength of Spry2 expression was evaluated using the immunoreactivity score (IRS), which was calculated using the following formula: IRS=(staining intensity score) SI×(percentage of positively stained cells) PP. The median IRS score was defined as the cutoff value. Patients were grouped as "weak immunoreactivity score" (IRS: 0 to 4) or "strong immunoreactivity score" (IRS: ≥4) with respect to the IRS score. RESULTS: The intensity and percentage of Spry2 staining were significantly lower in tumor tissues than in normal lung tissues ( P <0.0001). Patients' characteristics were similar for both groups, except for smoking status and, brain and lymph node metastasis. Overall survival of patients with a strong immunoreactivity score was significantly lower than those with a weak immunoreactivity score among metastatic patients (6.9 mo vs. 13.6, P =0.023) and adenocarcinoma histology (7.0 mo vs. not reached, P =0.003). CONCLUSION: Spry2 expression was lower in tumor tissues than in normal lung parenchyma. Increased expression of Spry2 is associated with poor prognosis. There were no significant associations between epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1 rearrangement and Spry2 expression. Despite the absence of KRAS mutational analysis, the clinical and epidemiological features of patients suggested that KRAS mutation might be an underlying determinant factor of the functional role of Spry2 in non-small cell lung cancer.

The Effect of HER2-Low Status on Pathological Complete Response and Survival in Triple-Negative Breast Cancer: A Systemic Review and Meta-Analysis.

This meta-analysis conducted a comprehensive analysis of research investigating the correlation between HER2 expression levels and treatment outcomes in early-stage triple-negative breast cancer (TNBC) patients. We systematically searched major databases for studies published up to January 01, 2023. The data from various studies examined the relationship between HER2-zero and HER2-low tumors in terms of pathological complete response (pCR) rates, disease-free survival (DFS), and overall survival (OS) outcomes. The odds ratio (OR) and 95% confidence interval (CI) by the number of events were calculated using the Mantel-Haenszel method to analyze pCR. The hazard ratio and 95% CI were calculated using the inverse variance method for DFS and OS. In all comparisons, I2 was 0% and no heterogeneity was detected. A total of 12 retrospective studies involving 4094 patients were included. Thirty-six percent of the patients were in the HER2-low group. All 12 studies were included in the pooled analysis for pCR, and there was no difference between HER2-zero and HER2-low (40% vs. 38%, respectively; pooled OR:1.01 95% CI 0.88-1.16; I2: 0%). Four studies were included in the pooled analysis for DFS and 3 in the OS analysis. DFS and OS were significantly better in the HER2-low group (pooled hazard ratio: 0.67 for DFS, 0.64 for OS). There was no difference between HER2-low and HER2-zero in terms of pCR in early-stage TNBC. However, HER2-low was found to be associated with prolonged DFS and OS. PROSPERO REGISTRATION NUMBER: CRD42023391002.

Toxic hepatitis in metastatic breast cancer patient using ribociclib and denosumab.

INTRODUCTION: Hepatotoxicity is observed due to cyclin-dependent kinase (CDK4/6) inhibitors used to treat hormone receptor-positive metastatic breast cancer. However, it should not be ignored that denosumab may be hepatotoxic, although it is rare. CASE REPORT: A 73-year-old female patient with breast cancer with axillary lymph node, adrenal gland and bone metastases was started on ribociclib letrozole and denosumab treatment. Ribociclib treatment was discontinued due to grade 4 hepatotoxicity during treatment, but liver function tests did not decrease. After discontinuation of denosumab treatment, alanine aminotransferase and aspartate aminotransferase values regressed to baseline values. MANAGEMENT AND OUTCOME: Despite the discontinuation of ribociclib treatment, other causes of liver toxicity were investigated due to persistence of hepatic transaminases and elevation. Autoimmune hepatitis markers were negative. Hepatobiliary USG did not reveal any pathological findings except hepatosteatosis. Liver biopsy was performed to determine the etiology. Pathology result was compatible with acute hepatocellular damage (in favor of toxic hepatitis). A decrease in liver values was detected after discontinuation of denosumab treatment. DISCUSSION: Although cases with improvement in liver enzymes have been reported after discontinuation of ribociclib, no improvement in hepatotoxicity was observed in our case. Since the liver biopsy was toxic hepatitis, it was thought that other drugs used by the patient might cause this toxicity, and a significant decrease was observed in liver values after discontinuation of denosumab. Denosumab-induced liver toxicity is very rare, and there are only a limited number of cases in the literature.

Efficacy and safety of concomitant chemo-endocrine therapy in neoadjuvant treatment of hormone-positive HER2-negative breast cancer: a systemic review and meta-analysis.

BACKGROUND: The rate of pathological complete response (pCR) with both chemotherapy alone (CT) and endocrine therapy (ET) in the neoadjuvant (Na) treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) is unsatisfactory. Limited data on neoadjuvant concomitant chemotherapy and endocrine therapy (NaCET) are available. RESEARCH DESIGN AND METHODS: In this meta-analysis analyzed the efficacy and safety of randomized controlled trials (RCT) comparing the use of NaCET in HR-positive/HER2-negative BC. A comprehensive search was performed on PubMed, Cochrane Library and EMBASE databases, and congress paper lists for studies published/presented until 1 December 2022. RESULTS: Five RCTs involving a total of 630 patients were included. A pooled analysis of the five studies demonstrated that the pCR ratio was numerically higher in the NaCET arm than in the NaCT arm, but the difference was not statistically significant (6.5% vs. 3.8%; OR:1.72, 95% CI 0.82-3.62). Nonetheless, the NaCET arm exhibited a significantly higher objective response rate (ORR) (82% vs. 72.7%; OR:1.77, 95% CI 1.20-2.62). There was no difference between the arms in terms of grade 3-5 adverse events. CONCLUSIONS: In HR-positive/HER2-negative BC, NaCET significantly increases ORR without an increase in serious adverse events. Although the pCR rate increased numerically, it was not statistically significant.

Clinical Features and Prognostic Factors of Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multicenter Study from the Turkish Oncology Group Kidney Cancer Consortium.

INTRODUCTION: We aimed to evaluate clinical features, prognostic factors, and treatment preferences in patients with non-clear cell renal cell carcinoma (nccRCC). METHODS: Patients with metastatic nccRCC were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. Clinical features, prognostic factors, and overall survival (OS) outcomes were investigated. RESULTS: A total of 118 patients diagnosed with nccRCC were included in this study. The median age at diagnosis was 62 years (interquartile range: 56-69). Papillary (57.6%) and chromophobe tumors (12.7%) are common histologic subtypes. Sarcomatoid differentiation was present in 19.5% of all patients. When the patients were categorized according to the International Metastatic RCC Database Consortium (IMDC) risk scores, 66.9% of the patients were found to be in the intermediate or poor risk group. Approximately half of the patients (55.9%) received interferon in the first line. At the median follow-up of 53.2 months (95% confidence interval [CI]: 34.7-71.8), the median OS was 19.3 months (95% CI: 14.1-24.5). In multivariate analysis, lung metastasis (hazard ratio [HR]:2.22, 95% CI: 1.23-3.99) and IMDC risk score (HR: 2.35, 95% CI: 1.01-5.44 for intermediate risk; HR: 8.86, 95% CI: 3.47-22.61 for poor risk) were found to be independent prognostic factors. CONCLUSION: In this study, survival outcomes are consistent with previous studies. The IMDC risk score and lung metastasis are the independent prognostic factors for OS. This is an area that needs research to better treat this group of patients and create new treatment options.

Comparison of HER2-zero and HER2-low in terms of clinicopathological factors and survival in early-stage breast cancer: A systematic review and meta-analysis.

BACKGROUND: The prognostic differences between HER2-zero and HER2-low breast cancer (BC) remain unclear. Purpose of this meta-analysis is to investigate the differences between HER2-low and HER2-zero in terms of clinicopathological factors and survival outcomes in early-stage BC. METHODS: We searched major databases and congress proceedings until November 1, 2022 to identify studies comparing HER2-zero and HER2-low in early-stage BC. HER2-zero immunohistochemically (IHC) was defined as score 0, while HER2-low was defined as IHC 1+ or 2+/in situ hybridization negative. RESULT: A total of 23 retrospective studies involving 636,535 patients were included. HER2-low rate was 67.5% in the hormone receptor (HR)-positive group, while this rate was 48.6% in the HR-negative group. In the analysis of clinicopathological factors by HR status, the proportion of premenopausal patients within the HR-positive group was greater in the HER2-zero arm (66.5% vs 61.8%), whereas grade 3 tumors (74.2% vs 71.5%), patients younger than 50 years of age (47.3% vs 39.6%), and T3-T4 tumors (7.7% vs 6.3%) within the HR-negative group was higher in the HER2-zero arm. In both the HR-positive and HR-negative groups, the HER2-low arm showed significantly improved results for disease-free survival (DFS) and overall survival (OS). The hazard ratios for DFS and OS in the HR-positive group were 0.88 (95% CI 0.83-0.94) and 0.87 (95% CI 0.78-0.96), respectively. In the HR-negative group, the hazard ratios for DFS and OS were 0.87 (95% CI 0.79-0.97) and 0.86 (95% CI 0.84-0.89), respectively. CONCLUSION: In early-stage BC, HER2-low is associated with better DFS and OS compared to HER2-zero, regardless of HR status.