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.

Triglyceride-Glucose Index: A Candidate Prognostic Marker in HR-Positive/HER2-Negative Metastatic Breast Cancer Patients Treated With CDK4/6 Inhibitors.

AIMS AND OBJECTIVES: Although cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i) are a vital part of the treatment of hormone receptor (HR)-positive/HER-2-negative metastatic breast cancer (BC), individuals have different sensitivities to CDK4/6i, indicating the need for biomarkers. The fasting triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance (IR). Herein, we investigated the prognostic significance of the fasting triglyceride glucose (TyG) index in HR+/HER2- metastatic BC patients treated with CDK4/6i plus endocrine therapy (ET). METHODS: About 333 patients with HR+/HER2-metastatic BC treated with CDK4/6i plus ET were analyzed retrospectively. The TyG index was calculated within 3 months before the initiation of CDK4/6i plus ET. The median value of 8.43 was taken as the cutoff for the TyG index. RESULTS: The median overall survival (OS) was 73.6 months (95% CI, 66.0-81.1) in the whole cohort. The progression-free survival (PFS) was significantly longer in the low-TyG subgroup than in the high-TyG subgroup (30.1 vs. 21.3 months, multivariate adjusted [HR] = 0.666, 95% CI, 0.450-0.987, P = .043). While the median OS was not reached in the low TyG subgroup, it was 69.0 months in the high TyG subgroup (multivariate-adjusted HR = 0.513, 95% CI, 0.281-0.936, P = .030). Although the ORR and DCR were numerically greater in the low-TyG subgroup, no significant differences were observed between the low-TyG subgroup and high-TyG subgroup (28.1% vs. 24.7%, P = .476; 83.2% vs. 80.1%, P = .463, respectively). CONCLUSIONS: These data imply that the TyG index could be a predictive biomarker for the therapeutic efficacy of CDK4/6is. Extensive prospective studies are needed to confirm these findings.

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 hypoxia-inducible factor-1 alpha expression on survival in patients with metastatic cervical squamous cell carcinoma treated with first-line chemotherapy and bevacizumab.

This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.

Efficacy and safety of bevacizumab in patients with low-grade serous ovarian cancer.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

Prognostic factors in non-metastatic HER2 'low' and HER2 'negative' breast cancer: single institute experience.

AIM: Comparison of prognosis and survival in human epidermal growth factor receptor 2 (HER2)-low and HER2-negative patients with early stage or locally advanced, hormone receptor-positive breast cancer. MATERIAL AND METHODS: In a retrospective single center study, the patients with early stage or locally advanced stage, hormone receptor (HR)-positive [estrogen receptor (ER) ≥ 1% and/or progesterone receptor (PR) ≥ 1%] and HER2 negative or HER2 low invasive breast cancer diagnosis were included. A total of 444 patients were included in the study. Patients were divided into two groups: HER2 negative and HER2 low. There were 235 (53%) patients in the HER2 negative group and 209 (47%) patients in the HER2 low group. RESULTS: The HER2 low group had significantly longer 5­year disease-free survival (DFS) than the HER2 negative group. The patients with lower Ki67 (< 20%) also had a longer 5­year DFS. CONCLUSION: Nonmetastatic HR+/HER2 low breast cancer patients had better DFS than HR+/HER2 negative ones. The Ki67 level and HER2 low status were independent prognostic factors. Randomized clinical trials are needed in early stage HER2 low breast cancer patients.

Higher TP53 somatic mutation prevalence from liquid biopsy analysis in ever smoker non-small-cell lung cancer patients.

OBJECTIVE: Cigarette smoking is a primary risk factor, linked to 80% of LC deaths. TP53, a key gene, is implicated in various cancers, with TP53 alterations in 36.7% of cancers. This research aims to investigate TP53 mutations detected in NSCLC patients by liquid biopsy and explore the relationship between these mutations and smoking history. MATERIAL AND METHOD: The study enrolled a total of 340 patients diagnosed with non-small cell lung cancer (NSCLC). For sequencing, the Illumina NextSeq 500 system was utilized. The oncogenicity of the variants was assessed according to the ClinGen/CGC/VICC SOP and the variants were categorized into four tiers according to AMP/ASCO/CAP. RESULTS: The most common mutations were in TP53 (48.7%), followed by EGFR, PIK3CA, and PTEN. Missense mutations were frequent, with TP53 and EGFR having higher rates in ever-smokers. No indels or complex mutations were found in ever-smokers. Patient age ranged from 20 to 86 years. Tier I-II variants were more common in ever-smokers, while Tier III variants were prevalent in never-smokers. TP53 mutations were more frequent in ever-smokers, showing a strong association with smoking. Domain distribution showed differences in PIK3CA. Transversion/transition ratios varied by gene and smoking status. DISCUSSION: The presence of TP53 mutations is strongly associated with both cigarette smoking and elevated Tv/Ti ratios. The tier status of TP53, EGFR, and PTEN variants does not show a specific domain distribution, but interesting associations are observed between the tier status and domain distribution in PIK3CA variants. Therefore, further comprehensive investigations are needed to explore this entity, as well as the underlying factors contributing to the increased Tv/Ti rates in the TP53 gene. Such research will provide deeper insights into the genetic alterations associated with smoking and tumor heterogeneity, ultimately aiding in the development of targeted therapies.

Comparison of the Efficiency of Induction and Adjuvant Chemotherapy in Patients with Locally Advanced Nasopharyngeal Cancer.

OBJECTIVE: To make a comparative evaluation of induction chemotherapy (ICT) or adjuvant chemotherapy (ACT) added to standard concurrent chemoradiotherapy in patients diagnosed with locally advanced nasopharyngeal cancer (LANPC) (Stage 3-4a patients, except T3N0). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, from April 2009 to June 2021. METHODOLOGY: Clinicopathological features of adult patients diagnosed with LANPC were recorded from the hospital's patient registry database. Patients without the medical records were excluded. An assessment of the effectiveness of induction or ACT added to standard definitive chemoradiotherapy (CRT) was performed, and the application cycles were evaluated. RESULTS: Seventy-four patients (71.6% male, mean age 50.8±11.7) with LANPC were included in the study. There is no statistical difference in progression-free survival (PFS) between patients who applied ICT (before CRT) and ACT (after CRT) (p = 0.61). Female patients and patients aged ≤50 years had better PFS as independent factors (HR=3.82, 95% CI 1.14-12.74, p = 0.029; HR: 1.06 95% CI 1.02-1.10, p = 0.002, respectively). Also, patients aged 50 years and younger and female patients had a statistically longer overall survival (OS) (p = 0.045, and p = 0.012, respectively). While there was statistically no significant difference in PFS according to the number of cycles for EBER-positive patients received adjuvant Cisplatin-5FU (CF); 3 cycles compared to 2 showed a statistically higher OS (p = 0.06, and p = 0.022, respectively).     Conclusion: LANPC patients were found to have a positive survival if they were young and females. There was a positive impact on survival of intensified adjuvant CF in EBER-positive nonkeratinising, undifferentiated LANPC patients. KEY WORDS: Locally advanced nasopharyngeal cancer, EBER, Induction chemotherapy, Adjuvant chemotherapy.

HIPEC in Ovarian Cancer: When and to Whom?

OBJECTIVE: To evaluate the optimal candidates for hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Health Sciences University, Dr. Abdurrahman Yurtasian Ankara Oncology Training and Research Hospital, Ankara, Turkey, between 2013 and 2021. METHODOLOGY: Ovarian cancer patients who underwent HIPEC and CRS for peritoneal involvement were included in this study. Thermosolutions were prepared as a closed system by using HT 2000 hyperthermic perfusion device. Then, cisplatin was applied at 100 mg/m2 at 42-42.5 °C for 60 minutes after CRS. RESULTS: A total of 47 patients were enrolled. The median age was 54 years (27-80) at the time of diagnosis. Forty (85.1%) patients had high grade serous carcinoma and 22 (46.7%) patients had clinical stage 3C disease. The median peritoneal cancer index (PCI) was 13 (3-24) in the whole population. HIPEC was applied as first-line treatment in 25 (51%) patients. Eleven (23.4%) patients had HIPEC in the post-neoadjuvant interval whereas 10 (21.3%) patients had it in platinum sensitive relapse. Median progression free survival (PFS) was 31(95% CI:11-50), 33 (95% CI:1-67), and 18 (95% CI:8-27) months in the primary, post-neoadjuvant interval, and platinum-sensitive relapse HIPEC groups, respectively. The patients with lower PCI (PCI<13) had significantly better OS than others with higher PCI (PCI>13, 145 months versus 42 months, p=0.034). CONCLUSION: HIPEC with CRS should be considered in selected serous carcinoma patients with peritoneal involvement, especially for the patients with primary ovarian cancer with lower PCI (PCI<13). KEY WORDS: Ovarian cancer, HIPEC, Peritoneal cancer index.

Efficacy and Safety of Combined Chemotherapy Regimens with Bevacizumab in Platinum-sensitive Ovarian Cancers.

OBJECTIVE: To determine the differences in terms of overall survival in platinum-sensitive ovarian cancer (PSOC) patients undergoing various chemotherapy protocols, and to demonstrate patient tolerance, toxicity, and efficacy data with the use of bevacizumab in different protocols. STUDY DESIGN: An observational study. Place and Duration of the Study: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, from January 2018 to January 2022. METHODOLOGY:  Patients aged 18 and above, who had received treatment for PSOC, were included in the study. Patients with platinum-resistant disease and those for whom bevacizumab usage was contraindicated were not enrolled in the study. RESULTS: For the 95 patients, the median age was 55 (34-78) years. Median follow-up are 39.7 (39.2-47.5) months. Median progression-free survival (PFS) of the patients are 10.8 (7.3-14.0) months for carboplatin-gemcitabine-bevacizumab (CGB), 10.9 (IQR 5.5-14.3) months in the carboplatin-liposomal doxorubicin-bevacizumab (CLdB) arms, and 6.1 (IQR 5.8-14.3) months in the carboplatin-paclitaxel-bevacizumab (CPB) group (p=0.79). The median overall survivals (OS) are 37.9 (IQR 33.3-46.9) months in the CGB arm, 41.0 (IQR 38.0-50.3) months CPB arm, and 41.3 (IQR 38.1-52.3) months in the CLdB arm (p=0.173). CONCLUSION: There was no difference in terms of overall survival among all three chemotherapy protocols. However, due to the difference in toxicity, the treatment should be selected on a patient-specific basis. Additionally, the use of bevacizumab at a dose of 7.5 mg/kg was demonstrated to be equivalent to using 15 mg/kg in terms of overall survival. This lower dose is also important to avoid financial toxicity. KEY WORDS: Bevacizumab, Ovarian cancer, Platinum-based chemotherapy, Tolerability, Adverse clinical events.

Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling.

OBJECTIVE: Hereditary cancer syndromes constitute 5-10% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer. MATERIAL AND METHOD: Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying BRCA1/2 variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the Sophia Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP. RESULTS: Pathogenic/likely pathogenic variants were detected in 172 (13.7%) of 1254 patients. After excluding the 46 BRCA1/2-positive patients, among the remaining 126 patients; there were 60 (4.8%) breast cancer, 33 (2.6%) colorectal cancer, 9 (0.7%) ovarian cancer, 5 (0.4%) endometrium cancer, 5 (0.4%) stomach cancer, 3 (0.2%) prostate cancer patients. The most altered genes were MUTYH in 27 (2.1%) patients, MMR genes (MLH1, MSH6, MSH, MSH2, PMS2 and EPCAM) in 26 (2%) patients, and ATM in 25 (2%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations. CONCLUSION: This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.

Vortex keratopathy associated with ribociclib.

INTRODUCTION: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are the new generation drugs that have been started to be used in our clinical practice recently. These drugs have been shown to have better progression-free survival compared to standard therapy in patients with hormone receptor-positive (HR) and human epidermal growth factor receptor 2 (HER-2)-negative breast cancer. The most common side effects of CDK 4-6 inhibitors are neutropenia, nausea, leukopenia, fatigue, and diarrhea. This case demonstrated vortex keratopathy in both eyes, a rare condition in patients with breast cancer treated with ribociclib. CASE REPORT: A 68-year-old female patient was diagnosed with locally advanced HR (+)/HER2 (-) breast cancer in March 2015. In June 2021, bone metastases were detected. The patient was started on ribociclib and fulvestrant. After three cycles of ribociclib and fulvestrant treatment, she was admitted with the complaint of blurred vision in her left eye. Slit-lamp biomicroscopy examination revealed subepithelial haze with central subepithelial whorls in both corneas, more in the left eye, and also a mild punctate epithelial staining was observed with the application of fluorescein dye. MANAGEMENT AND OUTCOME: Ribociclib treatment was immediately discontinued and no changes were observed in the cornea and vision levels during the one-month follow-up. DISCUSSION: Routine and regular follow-up eye examinations in breast cancer patients treated with ribociclib may benefit patients in our daily clinical practice and may help us to detect side effects at an early stage and to manage them more effectively.

Experiences of the combined use of Favipiravir in patients using Lorlatinib and Brigatinib.

INTRODUCTION: The SARS-COV-2 (COVID-19) pandemic is challenging the management of cancer patients. In this article, we present two patients diagnosed with anaplastic lymphoma kinase (ALK) + non-small cell lung adenocarcinoma (NSCL CA), infected with COVID-19, who had a previous multi-line therapy with Brigatinib and Lorlatinib, and received Favipiravir for their current infection. CASE REPORTS: A 58-year-old man and a 65-year-old woman were diagnosed as ALK ( + ) NSCL CA. Both patients received tyrosine kinase inhibitors (TKI) for lung cancer when diagnosed with COVID-19. No adverse effects were observed with the concurrent use of Favipiravir, an antiviral drug currently used for COVID-19 and TKI. MANAGEMENT AND OUTCOME: Considering the pharmacokinetic effects of favipiravir and the ALK inhibitor TKI's used on our cases (Brigatinib-Lorlatinib), the concurrent use of these drugs was safe and prevented the delay in the primary treatment of the malignancy of our patients. DISCUSSION: To our knowledge, these are the only reported cases diagnosed as ALK ( + ) NSCL CA who received favipiravir because of COVID-19 while using TKI, and both patients recovered completely without any side effects.

Platelet-to-Lymphocyte Ratio as an Indicator to Predict Decreased Carbon Monoxide Diffusion of the Lung in Patients with Testicular Cancer.

OBJECTIVE: To investigate whether the use of diffusing capacity of the lungs for carbon monoxide (DLCO) and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) could be used to predict bleomycin-induced pulmonary toxicity in patients with testicular cancer (TCa). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Ankara Oncology Training and Research Hospital, Turkey, between 2017 and 2020. METHODOLOGY: Data of 40 patients with TCa, who were followed at cancer centre from 2017-2020 and received 3-4 cycles of BEP protocol were retrospectively screened and included who met the criteria for inclusion in the study. All patients with TCa, who were older than 18 years of age and had no secondary malignancy and comorbidity, were included in this study. RESULTS: A statistically significant negative correlation was found between DLCO change and NLR, PLR (r:-0.558, p:0.002 for NLR; r:-0.462 p:0.012 for PLR). A statistically significant positive correlation was found between DLCO change and lymphocyte level (r:0.436, p:0.018). The NLR and PLR were statistically higher in the group with a decrease of ≥10% in DLCO compared to the group with no decrease or a decrease of ≤10% in DLCO (for NLR; 3.03 ± 1.45 and 1.68 ± 0.73, respectively, p = 0.005; for PLR 187.72 ± 66.90 and 124.72 ± 47.99, respectively, p = 0.008). Multivariate regression analysis showed a statistically significant relationship between PLR increase and a decrease of ≥10% in DLCO. CONCLUSION: PLR and LDH could be used as independent predictive biomarkers for DLCO decline which is used to identify bleomycin-induced pulmonary toxicity. Key Words: Bleomycin, Markers of inflammation, Platelet-to-lymphocyte ratio (PLR), Pulmonary diffusing capacity, Testicular cancer.

Clinicopathological features of non-carcinoid malignant epithelial appendix tumors and risk factors for recurrence, single-center experience.

Background: Non-carcinoid appendix epithelial tumors are rare. These tumors include low-grade and high-grade mucinous neoplasm also adenocarcinomas. We aimed to investigate the clinicopathological features, treatment, and risk factors of recurrence. Methods: Patients diagnosed between 2008 and 2019 were retrospectively analyzed. Categorical variables were expressed as percentages and compared using the Chi-square test or Fisher's exact tests. Overall survival and Disease-free survival of the groups were calculated by the Kaplan-Meier method, and the log-rank test was used to compare the survival rates. Results: A total of 35 patients were included in the study. Of the patients, 19 (54%) were women and the median diagnosis age of patients was 50.4 years (19-76). As for pathological types, a total of 14 (40%) patients were mucinous adenocarcinoma and 14 (40%) patients were Low-Grade Mucinous Neoplasm (LGMN). Lymph node excision and lymph node involvement were 23 (65%) and 9 (25%) patients respectively. The majority of patients were stage 4 (27, 79%) and 25 (71%) of these patients had peritoneal metastasis. A total of 48.6% patients had been treated with cytoreductive surgery and hyper-thermic intraperitoneal chemotherapy. Median Peritoneal cancer index value was 12 (2-36). The median follow-up time was 20 (1-142) months. Recurrence developed in 12 (34%) of patients. When risk factors for recurrence are considered, there was a statistically significant difference in appendix tumors with high-grade, adenocarcinoma pathology, ones with peritoneal cancer index ≥12 and not having pseudomyxoma peritonei. Median disease-free survival was 18 (13-22, 95% CI) months. Median overall survival could not be reached while the 3-year survival rate was 79%. Conclusion: The risk of recurrence is higher in high-grade appendix tumors, having peritoneal cancer index ≥ 12, not having pseudomyxoma peritonei and adenocarcinoma pathology. High-grade appendix adenocarcinoma patients should be followed closely for recurrence.

Evaluation of factors predicting pathologic complete response in locally advanced HER2 positive breast cancer treated with neoadjuvant pertuzumab, trastuzumab and chemotherapy; Real life data.

PURPOSE: Recently, neoadjuvant treatment approach has gained importance in locally advanced HER-2 positive breast cancer. Adding pertuzumab increases pathological complete response (pCR). In this study, we aimed to examine the clinicopathologic features that predict the pCR in patients receiving neoadjuvant pertuzumab, trastuzumab, and chemotherapy in locally advanced HER2 positive breast cancer. METHODS: Locally advanced HER2 positive breast cancer patients who were followed up in 4 different oncology centers and received 4 cycles of pertuzumab, trastuzumab and taxane were retrospectively evaluated. A total of 58 (92%) patients received anthracycline chemotherapy before combination of dual her-2 blockade and taxanes. Fisher's and chi-square tests were used for nominal variables and numeric data analyses. RESULTS: A total of 63 female patients were included in the study. Their median age was 46 years (21-75) and 40 (63.5%) patients were premenopausal. Median tumor size was 25 mm (2-70) and there were 22 (34.9%) patients with Stage 3a. pCR was 66% and 75% in the whole group and in the hormone negative group, respectively. Statistically significant increase was found in pCR in patients with grade 3 tumors and cerbB2 with 3+ immunohistochemical staining. No relationship was found between pCR and age at diagnosis, menopausal status, tumor infiltrating lymphocyte, dose-dense anthracycline, Ki67≥40, body mass index (BMI) ≥ 30 kg/m2 and accompanying DCIS. CONCLUSION: Four cycles of pertuzumab, trastuzumab and taxane after neoadjuvant anthracycline for locally advanced HER2 breast cancer are associated with increased pCR in patients with grade 3 tumors and high cerbB2 expression.

CROSS or FLOT in Distal Esophageal and Gastroesophageal Cancer.

OBJECTIVE: To compare the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) and continuous infusion 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) protocols administered in distal esophageal and gastroesophageal junction (GEJ) tumors in terms of effectiveness and toxicity. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Ankara Oncology Training and Research Hospital, Turkey between 2015 and 2020. METHODOLOGY: Patients diagnosed with distal esophageal and GEJ squamous cell carcinoma (SCC) or adenocarcinoma  (ADC), older than 18 years of age, in localised or locally advanced stage were included. Metastatic stages  were excluded. Kaplan-Meier was used for survival analysis, log-rank test was performed for comparisons between groups. RESULTS: A total of 25 patients (44.6%) were treated with CROSS protocol (15 distal esophageal and 10 GEJ tumor), 31 patients (55.4%) with GEJ tumors were treated with the FLOT regimen. Eight of the patients who were administered the CROSS protocol before the operation demonstrated complete pathologicial response, no patients in the FLOT group had complete response to the treatment. In patients with GEJ tumors and ADC histopathology, CROSS and FLOT group had similar second years survival (60% and 59.3%, respectively) (p = 0.803). The frequency of neutropenia was significantly higher in the CROSS group compared to the FLOT group (p = 0.004.) Conclusion: Postoperative pathological response rate in the CROSS group was significantly higher compared to the FLOT group. CROSS and FLOT protocols contributed to survival similarly in patients with GEJ ADC, hematological side effects were more pronounced in patients receiving CRT. Key Words: GEJ cancer, Esophageal cancer, Cross, Flot.

Clinical Outcomes and Prognostic Factors in HER-2 Positive Breast Cancer with Brain Metastasis: A Single-centre Experience.

OBJECTIVE:  To determine the characteristics and prognosis of brain metastasised HER-2 positive breast cancer (BC) patients. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Ankara Oncology Training and Research Hospital, Turkey between 2000 and 2019. METHODOLOGY: HER-2 positive BC patients were analysed retrospectively and 105 patients were included in the study. Age 18 years and over, HER-2 positive BC, with BM (brain metastases) were the inclusion criteria. Patients with secondary malignancies, those with missing data, and irregular follow-up were excluded from the study. The age, type of treatment, Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, BM date, and the last contact date of the patients were obtained from the hospital records. The Kaplan-Meier method was used to determine the time to BM and OS. Independent factors affecting OS and time to BM were determined using the Cox regression model. RESULTS: Patients with ECOG PS score of 0-1 at the time of the BM had 19 months median overall survival (OS), while patients with ECOG PS score of 2 had 8 months (p <0.01). Median OS after BM was 32 and 14 months for patients with one BM and patients with multiple BM, respectively (p <0.01). Multivariate cox regression analyses revealed that time to progression of BM was shorter in patients with high-grade tumors compared to patients with low-grade tumors (p= 0.048), and in patients with de-novo metastasis compared to patients without de-novo metastasis (p= 0.003). Conclusion: Tumor grade and de-novo metastasis (extracranial metastasis at the time of diagnosis) are independent predictive factors that may cause the earlier occurrence of BM and affect mortality in BC patients. Key Words: Brain metastasis, Breast cancer, HER-2 positive, Metastasis.

The Real-Life Data of BRAF Mutation on the Treatment of Colorectal Cancer: a TOG Study.

PURPOSE: Colorectal cancer is the third leading diagnosis accounting for nearly 10% of all new cancers worldwide. The distinct features among BRAF mutant colorectal cancers make these tumor groups hard to treat for oncologists. The median overall survival (OS) of these types of cancers is reported to be 9 to 14 months. METHODS: The study was declared on the Turkish Oncology Study Group Conference and approved. The patients' data was received from the centers who confirmed to participate. The BRAF-mutated patients were included in the study. The demographic features (age, gender, etc.), type of mutation, tumor localizations, histology, microsatellite instability (MSI) status, metastasis patterns chemotherapeutic agents and progression, and death times were recorded. RESULTS: Thirty-nine patients were enrolled in the study. Sixteen patients had concurrent KRAS mutations, while 7 had NRAS mutations. Most of the patients received doublet chemotherapies in combination with anti-VEGF agents in the first and second line of the treatment. There was a significant difference in OS according to the stage which showed a decreased survival in stage IV patients at the time of diagnosis. Concurrent KRAS mutation resulted in increased OS. The median OS was 47 and 24 months favoring the KRAS mutant group. The patients whose primary tumor operated had better survival when compared with other patients. The median OS of the operated group was 47 months, while the non-operated group was 24 months. Liver metastasis was related to worse prognosis at the time of diagnosis in univariate analysis. CONCLUSION: In our study we found a high concurrent RAS mutation ratio in a BRAF mutant patient group which was different from prior studies. The concurrent mutations resulted in a favorable outcome in terms of OS which is also different from the current knowledge. More prospective studies are needed especially BRAF-mutated patient population and especially with concurrent RAS mutations.

Worse patient-physician relationship is associated with more fear of cancer recurrence (Deimos Study): A study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

OBJECTIVE: Fear of cancer recurrence (FCR) is an important psychological trauma associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study was to evaluate the impact of patient-physician relationship on FCR. METHODS: The study was designed as a multicentre survey study. The cancer survivors, who were under remission, were evaluated with structured questionnaires. Patient-physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory was used. RESULTS: Between January and April 2019, 1,580 patients were evaluated. The median age was 57.0 (19-88), and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r = -.134, p < .001). In multivariate analysis, young age, female gender, history of metastasectomy and worse PPR were associated with high levels of FCR. CONCLUSION: It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practised. In addition, the cancer survivors, who are under the risk of FCR, should be evaluated and managed.