Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

Response to first-line chemotherapy regimen is associated with efficacy of immune checkpoint blockade therapies in patients with metastatic urothelial carcinoma.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. PATIENTS AND METHODS: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. RESULTS: The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS ≥ 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. CONCLUSIONS: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. PATIENTS AND METHODS: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. RESULTS: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. CONCLUSIONS: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

Outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

PURPOSE: To evaluate the potential benefit of curative radiotherapy (RT) to the primary tumor in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone. MATERIALS AND METHODS: The clinical parameters of 106 mCRPC patients treated with abiraterone were retrospectively evaluated. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after the systemic treatment was analyzed. Local RT to the primary tumor and pelvic lymphatics was delivered in 44 patients (41%), and 62 patients (59%) did not have RT to the primary tumor. After propensity match analysis, a total of 92 patients were analyzed. RESULTSN: Median follow-up time was 14.2 months (range: 2.3-54.9 months). Median overall survival (OS) was higher in patients treated with local RT to the primary tumor than in those treated without local RT with borderline significance (24.1 vs. 21.4 months; p = 0.08). Local RT to the prostate and pelvic lymphatics significantly diminished the local recurrence rate (16 patients, 31% vs. 2 patients, 5%; p = 0.003). In multivariate analysis, the prostate specific antigen (PSA) response ≥50% of the baseline obtained 3 weeks after abiraterone therapy was the only significant prognostic factor for better OS and progression-free survival (PFS). Patients treated with primary RT to the prostate had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT. CONCLUSIONS: Local prostate RT significantly improved OS and local control in mCRPC patients treated with abiraterone. The patients treated with primary RT had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.

The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

Currently, there are no predictive markers of response to abiraterone. We calculated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks in 102 metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone either pre- or postchemotherapy. With a median follow-up was 24.0 months (range: 0.3-54.9), median overall survival (OS) was 20.8 months. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. NLR and prostate-specific antigen response to abiraterone was a significant predictor of OS and progression-free survival (PFS) in metastatic castration-resistant prostate cancer patients treated with abiraterone delivered either pre- or postchemotherapy.

Genetic polymorphisms in human telomerase reverse transcriptase (hTERT) gene polymorphisms do not associated with breast cancer in patients in a turkish population: hospital-based case-control study.

Breast cancer (BC) is encountered most frequently in developed or developing countries. It is the most common cancer in humans following lung cancer, and it is the most common cancer type resulting in mortality in women. Genetic polymorphisms are among the genetic factors that play an important role in the development of the breast cancer. The purpose of this study was to investigate the effect of five functional single nucleotide polymorphisms (SNPs) of hTERT (rs2736109 G>A, rs2735940 T>C, rs2853669 A>G, rs2736098 G>A, and rs2736100 T>G) on susceptibility to BC in Turkish population. The genotype frequency of hTERT rs2736109 G>A, rs2735940 T>C, rs2853669 A>G, rs2736098 G>A, and rs2736100 T>G polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan methods in 123 subjects with GC and 122 healthy control subjects. The mean age value of the BC patients was 51.58±11.28 (among them 8 subjects ≤35 and 115 subjects >35). In this study, it was found that there was no statistical difference between hTERT rs2736109 G>A, rs2735940 T>C, rs2853669 A>G, rs2736098 G>A, and rs2736100 T>G polymorphisms that can be associated with risk of BC.

A functional HOTAIR rs12826786 C>T polymorphism is associated with breast cancer susceptibility and poor clinicopathological characteristics in a Turkish population: a hospital-based case-control study.

Hox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is pervasively overexpressed and correlated with tumor invasion, progression, metastasis, and poor prognosis in various human cancers including breast cancer (BC) that plays a role as an oncogenic molecule. A common functional single-nucleotide polymorphism (SNP) (rs12826786 C>T) at the HOTAIR promoter has been reported to influence HOTAIR expression and gastric adenocarcinoma susceptibility, but relation of HOTAIR rs12826786 C>T polymorphism with BC susceptibility and clinicopathological characteristics has yet to be reported. To explore the association of the HOTAIR rs12826786 C>T polymorphism with the risk of BC in a Turkish population, a hospital-based case-control study was carried out consisting of 123 BC patients and 122 age-matched healthy controls. HOTAIR rs12826786 C>T polymorphism was determined by real-time polymerase chain reaction (PCR) using TaqMan assay. We found that women carrying TT genotype of HOTAIR rs12826786 C>T polymorphism had an increased risk of developing BC in both codominant (odds ratio (OR) = 2.24, 95 % confidence interval (CI) 1.05-4.81, P = 0.02) and recessive (OR = 2.49, 95 % CI 1.25-4.97, P = 0.008) inheritance models. Moreover, TT genotype of HOTAIR rs12826786 C>T polymorphism was significantly related with multiple clinicopathological characteristics concerned with worse BC progression such as advanced TNM stage (III and IV), larger tumor size (T3 and T4), and distant metastasis (M1), as well as poor histological grade (III) (P < 0.05). Because of our results put forward for the first time that TT genotype of HOTAIR rs12826786 C>T polymorphism might play crucial roles in genetic susceptibility and poor prognosis for BC in Turkish population, further independent studies are needed to confirm our results in a larger series, as well as in patients of distinct populations.

A case of rectal adenocarcinoma presented with palatine tonsil metastasis.

The most common metastatic sites of colorectal cancer are liver, lung, peritoneum and lymph nodes. Metastasis of colorectal carcinoma to palatine tonsil is rarely seen. To our knowledge, only 11 patients were documented in English literature. Atypical metastases can sometimes lead to misdiagnosis. Precise diagnosis of atypical metastases requires a careful physical examination, good imaging method and comprehensive pathological evaluation. Here, we report a case of rectal adenocarcinoma presented with palatine tonsil metastasis.

An old enemy not to be forgotten during PET CT scanning of cancer patients: tuberculosis.

AIM OF THE STUDY: Positron emission tomography-computed tomography (PET CT) scan is commonly used in current medical oncology practice as an imaging method. In this study we present data from cancer patients who were followed at our clinic and suspected of having tuberculosis during PET CT scanning. After the biopsy, they were diagnosed with concomitant tuberculosis. MATERIAL AND METHODS: In this study, 14 patients who applied to our clinic and followed up due to cancer, and had PET CT scanning for the preliminary staging or further evaluation, were included. The patients were diagnosed with metastatic or recurrent disease, and their biopsy results revealed tuberculosis. RESULTS: The mean age was 57.8 years with SD (standard deviation) 13.1 years and gender distribution of 78.6% (n = 11) females and 21.4% (n = 3) males. None of the patients had tuberculosis in their personal history (0%). Among the patients, 5 (35.7%) were diagnosed with tuberculosis during the preliminary staging, whereas 9 (64.3%) were diagnosed during the follow-up after the treatment. The median time to tuberculosis diagnosis was 11 months (min-max: 3-24 months) after the treatment. The most commonly involved lymph nodes during PET CT scanning were mediastinal in 8 (64.3%), axillary in 3 (21.4%) and para-aortic in 3 (21.4%) patients. The mean SUVmax (maximum standardised uptake value) of lymph node involved by PET CT scanning was defined as 8.5 (SD 2.6). CONCLUSIONS: Despite all improvements in modern medicine, tuberculosis is still a serious public health problem. It should always be considered in differential diagnosis while evaluating PET CT scanning results of cancer patients, because it may cause false positive results.

Effect of HOTAIR rs920778 polymorphism on breast cancer susceptibility and clinicopathologic features in a Turkish population.

Overexpression of Hox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is associated with cancer cell proliferation, invasion, progression, and metastasis as well as poor survival in a variety of human cancers including breast cancer (BC). A common functional single nucleotide polymorphism (SNP) rs920778 (T → C) in the intronic enhancer of the HOTAIR has been reported to influence HOTAIR expression and cancer predisposition, but the association of HOTAIR rs920778 polymorphism with BC susceptibility and clinicopathological features has yet to be investigated. We genotyped HOTAIR rs920778 polymorphism in 245 Turkish women including 123 BC patients and 122 age-matched healthy controls by a real-time polymerase chain reaction (PCR) with the TaqMan assay. We found that the CC genotype of HOTAIR rs920778 polymorphism significantly increased the risk of BC in both codominant (odds ratio (OR) = 2.12, 95 % confidence interval (CI) 1.00-4.51, P = 0.05) and recessive (OR = 2.40, 95 % CI 1.22-4.73, P = 0.01) inheritance genetic models. Our research also indicated an association between the CC genotype of HOTAIR rs920778 polymorphism and clinicopathologic features of tumor, including advanced tumor-node-metastasis (TNM) stage, larger tumor size, distant metastasis, and poor histological grade (P < 0.05). Because our findings suggest for the first time that the CC genotype of HOTAIR rs920778 polymorphism might play important roles in genetic susceptibility to BC development and aggressiveness in a Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different populations.

MicroRNA 211 expression is upregulated and associated with poor prognosis in colorectal cancer: a case-control study.

Increasingly more evidence support the role of the microRNAs (miRNA) in tumorigenesis. The role of up/downregulation microRNA-211 (miR-211) during human tumorigenesis is still contentious and may exhibit tissue-specific regulatory manner, but the exhaustive mechanisms underlying its pro/anti-oncogenic effects remain to be unknown. Sixty-six patients that were diagnosed and operated with colorectal cancer (CRC) and sixty-five healthy cases that were age and sex compatible with them were included in our study. miRNA was isolated from the formalin-fixed paraffin-embedded (FFPE) tissues of all cases. The expression level of miR-211 in matched normal and tumor tissues of CRC group and healthy group was evaluated using a quantitative real-time RT-PCR (qRT-PCR). Based on the average miR-211 levels, two groups of low or high expression were formed in CRC group. Correlation of the patients' clinicopathological factors and survival was also analyzed. No statistically significant differences were found in miR-211 levels among tumorous and normal tissues of CRC patient group (P = 0.59). Also, no statistically significant correlation was determined between clinicopathological factors and miR-211 expression level in CRC group. However, miR-211 expression levels between the CRC group and the healthy group were determined to be of statistical significance (P < 0.0001). There were 33 (50 %) CRC patients that expressed low levels of miR-211 and 33 (50 %) CRC patients that expressed high levels of miR-211. A median survival between low levels of miR-211 group and high levels of miR-211 group was evaluated via Kaplan-Meier, and the difference was of statistical significance (P = 0.035). The univariate analysis of the factors that may affect survival indicated invasion depth (P = 0.063), lymphovascular invasion (P = 0.011), perineural invasion (P = 0.009), and miR-211 expression level (P = 0.041) presence to be effective. In the multivariate analysis of these factors with overall survival, only miR-211 expression level (P = 0.01) was effective on overall survival. Our results suggest for the first time that miR-211 expressed more in CRC patients than in healthy group could be a new prognostic biomarker in order to predict survival. Independent studies are needed to validate our findings in a larger series, as well as in cancer of different tissues.

Concurrent chemoradiotherapy with vinorelbine plus split-dose cisplatin may be an option in inoperable stage III non-small cell lung cancer: a single-center experience.

BACKGROUND: Concurrent chemoradiotherapy is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In this study we aimed to investigate the efficacy and toxicity of CCRT with split dose of cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) in patients with inoperable stage III NSCLC followed in our oncology clinic. MATERIAL AND METHODS: Medical records of 97 patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with cisplatin-vinorelbine were retrospectively analyzed. Cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) were administered on days 1, 8, 22, and 29 during radiotherapy. Two cycles of consolidation chemotherapy were given. All patient data, including pathological, clinical, radiological, biochemical, and hematological data, were assessed retrospectively using our database system. RESULTS: Our study included 97 unresectable stage III NSCLC patients who were treated with CCRT. Median age was 58 years old (range 39-75) and 87 (89.7%) of the patients were men. ECOG performance score was 0-1 in 93 patients (95.9%). Squamous histology, the most common histology, was diagnosed in 46 patients (47.4%). Median follow-up time was 23.8 months. Median progression-free survival (PFS) and median overall survival time (OS) were 10.3 months and 17.8 months, respectively. Objective response rate and clinical benefit rate were 75.3% and 83.5%, respectively. Distant and local relapse rate were 57.1% and 42.9%, respectively. Hematological and non-hematological grade 3-4 toxicities were seen in 13 (13.4%) and 16 (16.5%) patients, respectively. Six (6.1%) patients died due to toxicity. CONCLUSIONS: The results of this study suggest that split-dose cisplatin may offer fewer grade III-IV toxicities without sacrificing efficacy and could be an option in patients with inoperable stage III NSCLC during CCRT. Similar to past studies, despite high response rate during CCRT, distant relapse is the major parameter that influences patient survival in long-term in NSCLC.

miR-204-5p expression in colorectal cancer: an autophagy-associated gene.

MicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low- and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p = 0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p = 0.021 and p = 0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-204-5p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p = 0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.

Malignant pleural mesothelioma: a single-center experience in Turkey.

BACKGROUND: Malignant pleural mesothelioma is a rare lethal malignancy caused by asbestos exposure. It is more frequently seen in certain regions in Turkey. In this retrospective study, we aimed to analyse demographic, clinical, and pathological data and treatment-related features in 54 patients. MATERIAL AND METHODS: The study included 54 patients diagnosed with malignant mesothelioma that were followed and treated. RESULT: Of the 54 patients, 34 (55.6%) were male. The median age in men and women were 60.3 (38.2-77.2) and 65.8 (37.7-77.5) years, respectively. In 35 (64.8%), exposure to asbestosis was present. Epithelial type was found in 27 (50.0%), followed by mixed type in 7 (13.0%) patients, and in 20 (37.0%) patients the subtype could not be determined. The disease was staged as IV in 37 (68.5%) patients. In 28 patients (51.9%), it was right-sided and in 1 (1.9%) it was bilateral. The most frequent metastatic sites (in decreasing order) were lungs, mediastinum, diaphragm, liver, and thoracal wall. Of the 54 patients, 36 (66.6%) received 1st-line chemotherapy and 20 (37%) 2nd-line chemotherapy. Eighteen patients (33.3%) received radiotherapy; 11 (20.3%) with palliative intention and 7 (12.9%) with curative intention. Median overall survival (OS) was 12.03 months (95% CI 7.2-16.8). OS was not affected by sex (p=0.32), smoking history (p=0.51), alcohol consumption (p=0.36), family history (p=0.67), pleural effusion presence (p=0.80), operation (p=0.14), clinical stage (p=0.072), symptom at presentation (p=0.66), having mixed type histology (p=0.079), asbestos exposure (p=0.06), and type of 1st-line chemotherapy (p=0.161). On the contrary, it may be positively affected by good ECOG PS (0-1) (p<0.01), age below 65 (p=0.03), left-sided disease (p=0.01), receiving chemotherapy (p<0.01), having unilateral pleural effusion (p=0.018), and type of 2nd-line chemotherapy (p=0.025). CONCLUSIONS: OS of our patients was better than that found in the literature, seeming to be positively affected by early stages, better ECOG PS, age below 65 years, left side involvement, and having second-line chemotherapy with cisplatin-gemcitabine or 3M. Overall treatment success seems to be comparable to what is currently expected.

Can serial monitoring of serum Vascular Endothelial Growth Factor (VEGF), Nitric Oxide (NO), and Angiotensin II (ANGII) levels have predictive role during Bevacizumab treatment?

BACKGROUND: Standard treatment of colorectal cancer includes both cytostatic chemotherapy and targeted therapies. Bevacizumab, targeting the VEGF receptor, is one of the primary targeted therapies that achieve better response rate and survival rate as compared to combination chemotherapy. To the best of our knowledge, there is no established single marker that can be used as a predictive marker in bevacizumab therapy. MATERIAL AND METHODS: We enrolled 24 patients with the diagnosis of metastatic colorectal cancer in our study. During the study, 2 blood samples were drawn from patients before the first cycle and after the sixth cycle of bevacizumab therapy. Serum levels of VEGF, ANG II, and NO were recorded. RESULTS: While the change across VEGF levels was found to be a statistically significant decreasing trend (p=0.009), this decrease was not found to be correlated with treatment response and hypertension development. Additionally, no statistically significant difference was found in terms of NO and ANG II levels. CONCLUSIONS: This study showed a significant decrease in serum VEGF, but failed to show a significant change in NO and ANG II levels during bevacizumab treatment. Although no significant correlation was found between the presence of hypertension and markers, most patients (83%) had an increase in their blood pressure. Our results suggest that dynamic monitoring of NO and ANG II, along with VEGF, may not be useful as predictive markers for bevacizumab treatment in colorectal cancer.

Gemcitabine + platinum combination chemotherapy in patients with metastatic cancer who suffer from severe and irreversible hepatic impairment: a single center experience.

There is limited information on chemotherapeutic agent doses suitable for patients with metastatic cancer who suffer from and irreversible hepatic impairment and who could potentially benefit from chemotherapy and on their results. In this retrospective study, we aimed to share our center's experience of Gemcitabine + Platinum Combination chemotherapy in these patients. Data of 13 patients matching the criteria were analyzed. In our study the patients were treated with a dose of Gemcitabine + Platinum Combination, 50% of the original dose and the dose was increased gradually on the following days. Thirteen of one patient was given Gemcitabine & Carboplatin protocol and the others were given Gemcitabine & Cisplatin . In 42 chemotherapy cycles in total grade 3-4 thrombocytopenia occurred after 7 cycles, grade 3-4 neutropenia was not observed. While liver functions in 8 patients improved slightly, no change was observed in 2 patients and in 3 patients they deteriorated. Total survival period was calculated as 3.78 (95CI% : 0,17-7.54) months. As a consequence, Gemcitabine + Platinum Combination chemotherapy in patients with metastatic cancer who suffer from severe and irreversible hepatic impairment can be implemented when clinical benefits are expected.

Continuous distress in an oncology clinic in Turkey: should we make use of the distress thermometer mandatory as a precautionary measure for physicians?

PURPOSE: To study the data on the distress scale points (DSP) of patients in oncology clinics in relation to age, the reasons for admission to the hospital, the educational status and the family support. METHODS: Six hundred and fifty three patients diagnosed with malignancies were enrolled. All of the patients were asked to fill in a questionnaire that included data about their demographic characteristics, diagnoses, the cause of hospital admission and the educational status. The family support of each patient was observed and noted by clinicians and other healthcare providers during the clinical visits. RESULTS: The mean patient age was 54.8 years (± SD 13.7). Of the patients 314 (48.1%) were male and 339 (51.9%) female. The median DSP for the group that included patients <35 years of age was 3; this was 5 for the 36-49 age group, 4 for the 50-69 age group and 4.5 for the >70 age group. A statistically significant difference in DSP between these groups was noticed (p=0.035). The DSP for patients <35 years of age was lower than that of the other age groups. The median DSP for the patients presenting to the outpatient clinic for adjuvant therapy was 5; this was 5 for patients presenting for palliative therapy, and 3 in the active surveillance group, and a statistically significant relationship was determined between the DSP and the reason for admission to the outpatient clinic (p<0.001). The patients that had presented to the outpatient clinic for active surveillance had statistically significantly lower DSP compared to the other groups (p<0.05). CONCLUSIONS: Distress in oncology clinics seems to be continuous; thus, the use of distress thermometer as a precautionary measure for distress development in patients with malignancies should be mandatory to help medical oncologists understand the psychosocial needs of their patients and start to treat them as a human beings.

Real-world data on the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab: Turkish oncology group multicenter study.

We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 - 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Which patients with advanced cancer and biliary obstruction benefit from biliary stenting most? An analysis of prognostic factors.

BACKGROUND: Patients with advanced cancer may present with obstructive jaundice. Biliary stenting is the treatment of choice. However, which patients benefit most is not well-defined, yet. Our aim was to delineate the clinical factors affecting prognosis. MATERIAL AND METHODS: Charts of 140 patients with advanced cancer who underwent biliary stenting were retrospectively analyzed. Their median age was 63.5 years. Of these patients, 73 (52.1 %) were male, 32 (22.9 %) had ECOG PS 1 and 81 (57.9 %) had PS 2. The most frequent cancer types were cholangiocellular cancer (64, 45.7 %) and pancreatic cancer (36, 25.7 %). RESULTS: Median overall survival (OS) was 141 (95 % CI, 100.7-185.3) days. Female patients lived longer (161.0 vs. 124.0 days) (p = 0.036). Those patients with colorectal cancer lived the longest (667.0 days), followed by cholangiocellular (211.0 days), and gastric cancers (106.0 days) (p = 0.004). The distribution of primary diagnosis differed significantly between sexes: cholangiocellular cancer was present in 22 (30.1 %) out of 73 men and 42(62.7 %) out of 67 women (chi-square p < 0.001). There was a trend for longer overall survival if ALT (p = 0.08) and AST (p = 0.06) were normalized after stent insertion. Of the 137 patients, 63 (45.5 %) did not experience any complication. In 74 patients with complications, there were 39 (28.5 %) episodes of cholangitic infections and 35 (25.5 %) biliary obstructions. In three patients, we could not find data on infections. CONCLUSION: Underlying malignancy, hence the natural biology and the therapeutic expectations are probably the most important factors which must be considered during decision-making.