Pazopanib for metastatic soft-tissue sarcoma: A multicenter retrospective study.

PURPOSE: Soft tissue sarcomas are associated with a poor prognosis and low chemotherapeutic efficiency. Pazopanib is an orally available multi-tyrosine kinase inhibitor that was explored in patients with non-adipocytic advanced soft tissue sarcomas. The aim of this retrospective study was to evaluate the real life data of single-agent pazopanib efficacy and safety for soft tissue sarcomas in the Turkish population. MATERIALS AND METHODS: We evaluated a total of 103 patients (41 males, 62 females) who received pazopanib for advanced non-adipocytic soft tissue sarcomas diagnosis in eight centers of Turkey, retrospectively. The pazopanib dose was 800 mg once daily. Progression-free survival, overall survival, and adverse events were analyzed. RESULTS: The median age was 50 years (range, 38-58). Majority of the patients had leimyosarcoma (41%). Median progression-free survival was 4.3 months, and the median overall survival was 10.1 months. The main common toxicities were fatigue, anorexia, weight loss, nausea, hypertension, and grade ≥3 toxicities were fatigue, anorexia, weight loss, and liver disorder. CONCLUSION: Pazopanib is an efficient and tolerable agent and is well tolerated in good performance status patients with relapsed, advanced non-adipocytic soft tissue sarcomas.

Comparison of survival with somatostatin analog and chemotherapy and prognostic factors for treatment in 165 advanced neuroendocrine tumor patients with Ki-67 20% or less.

The objectives of this study were to compare progression-free survival (PFS) with somatostatin analog (SSA) versus chemotherapy (CTx) in first-line therapy and to determine the patient group in which these treatments were more effective in neuroendocrine tumors (NETs) with a Ki-67 index of 20% or less. Patients who received SSA or CTx and had unresectable locally advanced and metastatic NETs with a Ki-67 index of 20% or less were retrospectively selected from 13 centers in the Turkish database between 2000 and 2015. One hundred and sixty-five patients were enrolled. The median age was 56 years and the male-to-female ratio was 1.09. Seventy-four (45%) patients were of grade 1 NET and 91 (55%) were of grade 2. SSA was given to 104 patients, whereas 61 were treated with CTx. The objective response rate after SSA was 15.4%; another 73.1% had stable disease. The objective response rate after CTx was 36.1%, and 40.9% had stable disease (P=0.008). The median PFS in SSA patients was 21 months (95% confidence interval: 12.4-29.6), and 8 months for CTx (95% confidence interval: 5.5-10.6) (P<0.001). There was no significant difference between PFS of receiving SSA and CTx in pancreatic neuroendocrine tumor (PNET) patients; however, the PFS of receiving SSA was longer in non-PNET patients (P<0.001). SSA was better treatment in advanced NET patients with a Ki-67 index of less than 5%, having a primary resected and a performance status of 0 (P<0.05). SSA may be preferred over CTx in advanced NET patients with low-to-intermediate grade.

Targeted therapy with anaplastic lymphoma kinase inhibitors in non-small cell lung cancer even with brain metastasis.

The incidence of brain metastases has increased as a result of improved systemic disease control and advances in imaging. Brain metastasis can occur approximately in 25-40% of the patients with non-small cell lung cancer (NSCLC) and it is a frequent cause of death. Stereotactic radiosurgery, whole-brain radiotherapy (WBRT) or surgical resection are the local treatment modalities for brain metastases which are feasible either alone, in combination, or as sequential treatments. Resistance to systemic therapy for brain metastasis poses significant clinical problems. In anaplastic lymphoma kinase (ALK)-positive NSCLC patients; ALK inhibitors may provide a new treatment option for brain metastasis and could improve overall survival (OS). Even in patients with crizotinib-resistant disease, second generation ALK inhibitors display prominent clinical activity. There is rapidly emerging preclinical and clinical data showing improvement in this issue. In this article we reviewed the latest literature data concerning the brain metastases and intracranial efficacy of ALK inhibitors in patients with ALK-positive NSCLC.

Diffusion tensor imaging: survival analysis prediction in breast cancer patients.

PURPOSE: We aimed to explore the performance of diffusion-tensor imaging (DTI) and apparent diffusion coefficient (ADC) parameters in evaluating disease-free survival (DFS) and overall survival (OS) in patients with invasive breast cancer. MATERIAL AND METHODS: A total of 49 women with invasive breast cancer who were diagnosed between 2017 and 2022 were included. All patients underwent breast magnetic resonance imaging (MRI) with DTI and diffusion-weighted imaging (DWI) features, with examiners blinded to the clinical data. Volume anisotropy (VA), fractional anisotropy (FA), and ADC values were measured to assess intratumoral measured heterogeneity. Correlations and differences in diffusion metrics according to OS and DFS status of the cases were analyzed. The discriminative ability of the quantitative findings was assessed by receiver operating characteristic (ROC) curve analyses and validated in the independent cohort. RESULTS: We evaluated patients with metastases (n = 13, 36.5%) and those without metastases (n = 36, 73.5%). Differences in the ADC, FA, and VA values were observed. The results of Cox regression survival analysis for all the patients included in the survival analysis revealed that DTI metrics contributed to the prediction of overall survival (OS) in the emerging models (p < 0.05). Both FA and VA were associated with OS (p = 0.037 and p = 0.038, respectively). However, ADC was not associated with OS (p = 0.177) or DFS (p = 0.252). CONCLUSION: To the best of our knowledge, this is the first study to assess the prognostic value of DTI-MRI in breast cancer with statistical survival analysis techniques. We believe that DTI measurements can be used as a biomarker for OS analysis in breast cancer given the available data.

Comparison of real-life data from patients with NGS panel negative and KRAS mutation positive metastatic lung adenocarcinoma.

OBJECTIVE: To evaluate clinical and demographic characteristics and the results of cytotoxic treatments of KRASG12C, KRASother, and next-generation sequencing (NGS) panel negative patients. METHODS: NGS data of 1264 patients with non-small cell lung cancer were retrospectively evaluated. Among these patients, the mutation distributions of 1081 patients with metastatic lung adenocarcinoma were analyzed. A total of 150 patients with negative NGS panel or mutant KRAS followed up in our clinic were included. Clinical features, overall survival, first-line chemotherapy responses, and progression-free survival of NGS panel negative, KRASG12C, and KRASother groups were compared. RESULTS: In 1081 patients who underwent NGS from tumor tissue with the diagnosis of metastatic lung adenocarcinoma, 296 (27%) NGS panel negative and 276 (26%) KRAS mutant patients were detected. Among these patients, 150 patients whose data were available were 71 (47.3%) NGS panel negative, 54 (36%) KRASother, and 25 (16.7%) KRASG12C. Clinical features, brain metastasis, and first-line chemotherapy response were similar among groups. Bone metastases were detected more often in the NGS panel negative group (p = 0.03). The median follow-up was 8.4 months. Overall, 107 deaths had occurred at the time of analysis. There was no difference in overall survival (p = 0.56) or progression-free survival (p = 0.71) among NGS panel negative, KRASother, and KRASG12C patients. CONCLUSION: There is no difference in overall survival, first-line chemotherapy response, or progression-free survival among patients with NGS panel negative, KRASG12C, or KRASother metastatic lung adenocarcinoma. Bone metastases were observed more frequently in the NGS panel negative group.

The relation between tissue galectin-3 level and platinum resistance in neoadjuvant bladder cancer treatment.

PURPOSE: This study aimed to reveal the relationship between the level of galectin-3 expression and the depth of response to neoadjuvant therapy in bladder tumor tissue with muscle invasion revealed by transurethral biopsy. METHODS: The percentage of galectin-3 staining in transurethral biopsy tissue with muscle invasion was determined by immunohistochemistry. The patients were divided into two groups: the down-staging (+) group consisting of patients with pathological complete response or non-invasive bladder cancer, and the down-staging (-) group consisting of patients with stage 2 and above. RESULTS: There were 11 patients in the down-staging (+) group and 12 patients in the down-staging (-) group. There was no significant difference between the two groups in terms of median age, gender, smoking, clinical stage at the time of diagnosis, distribution of carboplatin or cisplatin used as a platinum agent. Galectin-3 was positive in 2 patients (18.2%) in the group where down-staging was achieved with neoadjuvant therapy, while it was positive in 9 patients (75%) in the other group (p = 0.01). The median follow-up period of the patients was 31.6 months (95% CI 25.1-39.3). Overall survival was 43.4 months in the down-staging (+) group (95% CI 25.1-61.6) and 31.6 months in the down-staging (-) group (95% CI 12.7-50.6). Although there was a numerical difference, it did not reach statistical significance (p=0.37). CONCLUSION: The rate of down-staging after platinum-based neoadjuvant chemotherapy is significantly higher in patients with low galectin-3 staining in transurethral bladder biopsy tissue.

Receptor discordances after neoadjuvant chemotherapy and their effects on survival.

PURPOSE: To determine estrogen, progesterone and HER2 receptors' discordances after neoadjuvant chemotherapy in patients with locally advanced breast cancer and their effects on survival. METHODS: Data of 186 patients who were admitted to our oncology departments between 2000 and 2014, were retrospectively evaluated. Patients'status of hormone and HER2 receptors were assessed before and after neoadjuvant chemotherapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier and Log-rank tests were used, as appropriate. P<0.05 was considered as statistically significant. RESULTS: Median follow-up was 35 months. Of the patients, 20% had stage II disease and 80% stage III disease. Also, 74% showed hormone receptor positivity and 42% had HER2 overexpression. Hormone receptor discordance was detected in 63 (34%), HER2 discordance was detected in 33 (18%), and any receptor discordance was detected in 74 (40%) patients. There was a statistically significant difference regarding 5-year disease-free survival (DFS) between groups with loss of HER2 overexpression and without loss of HER2 overexpression (p=0.003). Five-year DFS was 60% with loss of any positive receptor status after chemotherapy and 72% with no change in any receptor status (p=0.023). In multivariate analysis, clinical stage (HR: 3.3, 95% CI: 1.18-9.3, p=0.022), changing HER2 status from positive to negative (HR: 2.6, 95% CI: 1.3-5.1, p=0.005), and triple-negative receptor status (HR: 2.64, 95% CI: 1.3-5.6, p=0.001) had significant impact on DFS. CONCLUSION: In patients with locally advanced breast cancer, loss of HER2 overexpression is an independent risk factor for DFS. Further studies are needed to determine the impact of receptor discordances.

Addition of taxanes to combination chemotherapy in distal intestinal gastric cancer is more beneficial than proximal ones: A multicenter retrospective study of Turkish Oncology Group.

PURPOSE: Advanced gastric cancer has a dismal prognosis. Platin/5-fluorouracil (PF) combination chemotherapy is the main treatment modality for metastatic gastric cancer patients. Third drug addition to PF is a controversial issue. The aim of this study was to evaluate the predictive role of tumor localization and histopathology on choosing three- or two-drug combination regimens. METHODS: This study was designed as a hospital-based retrospective observational case-series study. A total of 516 patients with advanced gastric cancer has been treated at eight different oncology centers in Turkey between 2006 and 2016. Laboratory results and demographic data were collected and analyzed. RESULTS: The median patient age was 59 years (range 25-85). Proximal intestinal and distal intestinal cancers were found in 357 (69.2 %) and 159 (30.8 %) patients, respectively. 5-fluorouracil (5FU) and cisplatin (PF) and cisplatin+5FU+docetaxel (PFtax, also known as DCF) were administered to 240 (46.5%) and 276 (53.5%) patients, respectively. Median progression free survival (PFS) was 5.0 (95% CI 4.21-5.29) and 8 months (95% CI 7.22-8.77) for PF and PFtax groups, respectively (p=0.000). When tumor localization was used as stratum in PFS survival, PFtax produced significantly higher PFS rates only in distal intestinal type gastric cancer compared to PF (p=0.000). Median overall survival (OS) was 12 (95% CI 9.8-14.2) and 16 months (95% CI 13.6-18.4) for the PF and PFtax groups, respectively (p=0.01). When tumor localization was used as stratum in OS, PFtax showed significantly higher OS rates only in the distal intestinal type gastric cancer compared to PF (p=0.01) Conclusion: Pathology and tumor location in gastric cancer may affect the outcome. Addition of taxanes as a third drug may significantly increase PFS and OS rates only in distal intestinal type gastric cancer but not in patients with proximal type gastric cancer.

A retrospective analysis on first-line bevacizumab, cetuximab, and panitimumab-containing regimens in patients with RAS-wild metastatic colorectal cancer: A Collaborative Study by Turkish Oncology Group (TOG).

PURPOSE: To compare the efficacy and adverse effect profiles of the first-line treatment of patients with KRAS wild type metastatic colorectal cancer (CRC) in Turkey who were treated based on regimens including bevacizumab, cetuximab and panitumumab. METHODS: This retrospective multicenter observational study involved a total of 238 patients who received chemotherapy in combination with either bevacizumab or cetuximab or panitumumab as first-line therapy for KRAS wild-type metastatic colorectal cancer. Patients with full medical records having pathological diagnosis of CRC adenocarcinoma were included in the study. The demographic, laboratory, histopathological and clinical characteristics of the patients were determined, and three groups were compared based on the study variables. RESULTS: The mean age of the entire sample (n=238) was 58±11 years, 64% of which were male. The most frequent tumor localization was the rectum (37%) and G2 was the most common tumor grade (59.7%). About 63% of the patients had metastatic disease at diagnosis, with the most common site of metastasis being lung (14.7%) and liver (52.5%). Overall survival (OS) was 63.9%, while 1-, 3- and 5-year survival rates were 91.7, 56.6 and 36.9%, respectively. The expected mean survival was 49.1 months (95% CI, 42.9-55.3). The 1-, 3- and 5-year progression-free survival (PFS) rates following first-line treatment were 65.3, 26.1 and 5.6%, respectively, while disease free survival (DFS) in patients without metastasis at diagnosis was 68.5%. An analysis carried out disregarding which treatment the patients received (FOLFOX or FOLFIRI) revealed that a panitumumab-containing combination resulted in poorer prognosis compared to bevacizumab or cetuximab-containing combination (p<0.001). With regard to the adverse effect profile, the most common adverse effects were neuropathy and neutropenia in patients receiving FOLFOX-bevacizumab; neutropenia and perforation in patients receiving FOLFIRI-bevacizumab; rash and pustular infection in patients receiving FOLFIRI-cetuximab; and diarrhea in patients who received FOLFIRI-panitumumab combination. CONCLUSION: This is the first multicenter study performed in Turkey evaluating the response to treatment and adverse effects in patients with KRAS wild-type metastatic colorectal cancer.

Invasive Pleomorphic Lobular Histology Is an Adverse Prognostic Factor on Survival in Patients with Breast Cancer.

Invasive pleomorphic lobular carcinoma (IPLC) is defined to be an uncommon and different subtype of classical invasive lobular carcinoma (ILC). This special variant is characterized by significant cytological atypia and pleomorphism which differs from the cytological uniformity of ILC. IPLC has been shown to have some poor prognostic factors such as axillary node metastasis and higher histological grade which may lead to poor clinical courses including a short relapse time, increased risk of recurrence and a decreased survival. The aim of this study is to investigate the clinicopathological characteristics and prognosis of IPLC in comparison with ILC and also to evaluate if IPLC is a different clinical entity compared to ILC. A total number of 4418 breast cancer patients treated between 1996 and 2015 in Hacettepe University Cancer Institute, were retrospectively analyzed. Among 4418 patients, 210 were diagnosed with ILC and 23 patients diagnosed with pure IPLC. In this present study, clinicopathological characteristics, disease free survival (DFS) and overall survival (OS) of patients with ILC and IPLC were compared. This study design is one of the rare face to face comparison of pure IPLC and ILC. Patients with IPLC had an increased rate of higher histologic grade, extracapsular extension, lymphovascular invasion and lower percentage of hormone positivity than those of patients with ILC. During the follow-up time, IPLC group experienced 4 cases (17.3%) of recurrence, 5 cases (21.7%) of death and 2 cases (8.7%) of progression in 3 metastatic patients compared to that of 27 cases (12.9%) of recurrence, 29 cases (13,8%) of death and 14 cases (6.7%) of progression in 19 metastatic patients in the ILC group. Patients with IPLC had a worse DFS and OS duration than patients with ILC (P = 0.02 for OS, P = 0.04 for DFS). In conclusion, IPLC is a different and a special breast cancer subtype. This study suggests that IPLC is a distinct clinical entity with an advanced stage and more aggressive clinical course. Patients with IPLC reveal poorer prognostic factors such as higher histological grade, relative lower percentages of hormone positivity, and increased rate of recurrences resulting in poor clinical outcomes and worse survival. Nowadays, it is observed that current treatment methods for IPLC do not seem as successful as in ILC and failed to be effective. Thence, individual therapies including more aggressive surgery and adjuvant or neoadjuvant chemotherapy even in the earlier stages of breast cancer should be performed for this distinct variant.

K-RAS and N-RAS mutations in testicular germ cell tumors.

Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs) are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS) gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55%) pure seminoma cases and 19 (45%) non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen). In total, a RAS mutation was present in 12 patients (27%): 7 seminoma (29%) and 5 non-seminoma cases (26%) [p = 0.55]. A K-RAS mutation was present in 4 pure seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.