Gökhan Demir’s research while affiliated with Istanbul Surgery Hospital and other places

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce. We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey. This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024. The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33–60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n = 8), followed by NTRK3 (n = 7). The median duration of entrectinib usage was 6.9 (IQR 3.1–16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2–62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0–30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0–48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0–13.5) months. In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.

Despite the high prevalence of lung cancer among other primary tumors, metastasis of this particular malignancy in the breast is very rare. We report three new cases of lung cancer with breast metastases and discuss radiological and clinical findings. Radiologically, each case displayed different characteristics. First, one of them had bilateral superficially and deeply located irregular lesions. Second, the patient presented with findings similar to inflammatory breast cancer. The third case had a circumscribed mass, resembling a benign complicated cyst. To guide clinicians for proper patient management, radiologists should be aware of the scope of typical and atypical imaging findings of metastatic involvement of the breast.

Spontaneous colonic perforation (SCP) is a life-threatening complication of bevacizumab treatment, but data on its management is insufficient. We present five cases of SCP in patients who were receiving bevacizumab for extra-intestinal malignancies. Patients who underwent a partial colectomy at the perforation site (n=3) suffered from ongoing abdominal sepsis postoperatively and died within a month. In contrast, patients who underwent total colectomy (n=2) had a relatively prolonged survival and eventually died of primary disease progression. Considering the pathophysiology of bevacizumab-related SCP, a total colectomy can be a life-saving and definitive procedure when non-perforated segments of the colon appear unhealthy during intraoperative exploration.

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population

Introduction: The synthesis of CDK4/6 inhibitors with treatment of endocrine in start two series of treatment has been widely accepted as the standard for Esterogen (ER)-positive MBC (metastatic breast cancer) patients. In spite of, the activity of CDK4/6 inhibitors in MBC patients who had progressed despite receiving multiple lines of treatment is not well understood. Aim: We aimed to report on the activity and safety of a CDK4/6 inhibitor (palbociclib) for patients who had failed at least three lines of treatment for ER+/ MBC. Study design: Multi-center retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients, whom were given palbociclib after at least 3 lines of systemic treatment for ER-positive/HER2-negative MBC. Results: Overall, the median progression-free survival in our population was 7 months (25th percentile = 4, 75th percentile = 10) (Figure 1) and median overall survival was 11 months (25th percentile = 6, 75th percentile = 19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only 6 (14%) patients. Conclusion: We demonstrated that the efficacy of palbociclib among heavily treated hormone receptor-positive/HER2-negative advanced BC patients was acceptable clinical benefit, and it was generally well tolerated among this population.

Aim of the study: Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods: Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results: Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12-61) and 19 months (5-45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions: As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients.

This study aimed to determine the epidemiological characteristics of colorectal cancer in Turkey. In this multicenter, prospective, and cross-sectional registry study, data for 968 patients with colorectal cancer from 21 centers in 7 geographic regions were analyzed. Diagnosis was colon cancer in 662 (68.4%) and rectum cancer in 306 (31.6%) patients. In total, 60.9% of patients was male; mean age was 58.9±12.6 years. Among patients, 15.0% was drinking alcohol, 17.5% was smoking, 1.5% had familial history of polyposis, 15.0% had diabetes mellitus, 1.0% had inflammatory bowel disease. Fruit and vegetable consumption was low (<3 times/week) in 35.5% and red meat consumption was high (≥3 times/week) in 47.4% of the patients. Median time-to diagnosis was 3.0 months and 4.0 months for patients with colon and rectum cancer, respectively. Mean body mass index was >25 in all group of patients. Distal rectum (61.3%) and sigmoid colon (36.8%) were the most common locations of cancer, for rectum and colon respectively. In total, 85.6% of patients were operated; 25.8% had emergency surgery. Low anterior resection rate was 64.2% in rectum cancer. In majority (89.8%) of the patients with rectum cancer who received preoperative treatment, conventional chemo-radiotherapy regimen was given. pTNM staging at diagnosis showed that stage III and IV patients were in majority (35.9% and 29.7%, respectively). Colon cancer is more frequent than rectum cancer in Turkey. Colorectal cancer patients are diagnosed at later stages. Most of the cases were operated. Interregional differences for risk factors are worthwhile for evaluation in future trials.

Neurological involvement is observed in 5%-25% of patients with lymphoma being either the first presentation of the disease or emerging during its course. However, Guillain-Barr? syndrome is rarely reported. In this article, we present a case with intestinal lymphoma developing Guillain-Barr? syndrome during the course of the disease. A 66-year-old male patient with primary extranodal intestinal lymphoma developed quadriparesis, sensory deficits and autonomic dysfunction while receiving chemotherapy. The findings of clinical, electrophysiological and laboratory examinations were consistent with Guillain-Barr? syndrome. Guillain-Barr? syndrome can potentially be fatal and mimic chemotherapy-induced neurotoxicity, especially in patients with lymphoma, and therefore, must be considered in the differential diagnosis.

Refractory malignant ascites (MA) is a common complication in cancer patients. Renal cell carcinoma (RCC) is rarely present with peritoneal ascites, which is commonly associated with carcinomas of the gastrointestinal and female reproductive tracts; including especially ovarian high-grade serous carcinoma. Currently, chemotherapy and paracentesis represent the most widely used methods to relieve the symptoms. Recently, intraperitoneal therapy with catumaxomab-a trifunctional hybrid antibody-has been introduced for the treatment of MA. The benefit of this treatment has been demonstrated in patients with distinct abdominal malignancies. In this case report, we present the first case of successful catumaxomab treatment against MA in a patient with advanced RCC with sarcomatoid differentiation. After the second administration of catumaxomab, paracentesis became no longer necessary. Catumaxomab might represent a safe treatment option for MA in the course of metastatic RCC with sarcomatoid differentiation.