Survival outcomes of patients with oligometastatic non-small cell lung cancer who were treated with radical therapy: a multicenter analysis.

BACKGROUND: Oligometastatic disease for nonsmall cell lung cancer (NSCLC) patients is generally thought to represent a better prognosis with a quieter biology, limited number of disease sites and long-term disease control. In this study, we aimed to determine the efficacy of radical treatment options for patients with oligometastatic NSCLC. METHODS: This retrospective trial included totally 134 patients with oligometastatic NSCLC. The presence of oncodriver mutation, tumor stages and nodal status, the number of metastases and involved metastatic site, treatment of primary tumor and oligometastasis, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: Of 134 patients 66.4% were defined as adenocarcinoma, 26.1% were squamous cell carcinoma and 7.5% of patients were in other histology. Based on the treatment of primary tumor, in 36 patients (26.9%) curative surgery has undergone, in addition, 19 (14.2%) patients were received chemotherapy, 73 (54.5%) were treated with chemoradiotherapy, while immunotherapy and targeted therapy were used in 1 (0.7%) and 2 (1.4%), respectively. The preferred treatment for oligometastatic lesions were SBRT in 72.4% of patients, surgery in 10.5%, and both SBRT and surgery in 17.1% of patients. At the median follow up of 31.3 months (range: 9.5-48.5), the median PFS and OS times were 17 and 24.4 months, respectively. Moreover, OS-2 after progression was also 7.2 months. DISCUSSION: Based on our real-life experience, we demonstrated a significant correlation between good response to first treatment and survival in oligometastatic disease, we also understand that local ablative treatment modalities prolong and also delay both OS and PFS in oligometastatic NSCLC patients OS-2.

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.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

OBJECTIVE: Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). MATERIAL AND METHOD: We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. RESULTS: Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. CONCLUSION: TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

Is the prognostic nutritional index a prognostic and predictive factor in metastatic non-small cell lung cancer patients treated with first-line chemotherapy?

PURPOSE: We aimed to assess the prognostic and predictive significance of pretreatment Onodera's prognostic nutritional index (OPNI) in metastatic non-small cell lung cancer patients (NSCLC) treated with first-line chemotherapy. MATERIALS AND METHODS: Patients with metastatic NSCLC who attended five different medical oncology clinics between December 2008 and January 2018 were retrospectively analyzed. The optimal cut-off point for OPNI was performed by a receiver operating characteristic (ROC) curve analysis. Patients were assigned to either the low OPNI group or high OPNI group. RESULTS: A total of 333 patients were included in the study. Significant differences between the low and high OPNI groups were found regarding the rates of response to chemotherapy, sex, and hemoglobin level (p < 0.05). The patients in high OPNI group had a longer overall survival (OS) (15.3 vs. 10.6 months, p < 0.001) and progression-free survival (PFS) (6.7 vs. 5.3 months, p < 0.001) compared to the patients in low OPNI group. A multivariate analysis using Cox regression model revealed that a high OPNI score was an independent prognostic factor of OS (HR = 1.535, p = 0.002) and PFS (HR = 1.336, p = 0.014), but failed to demonstrate a statistical significance of pretreatment OPNI scores in predicting treatment response (p = 0.56). CONCLUSIONS: Pretreatment OPNI is an independent prognostic factor for OS and PFS in metastatic NSCLC patients treated with first-line chemotherapy. Thus, it may be used as easily calculated and low-cost prognostic tool in the routine clinical practice in this patient group.

Real-world outcomes of pazopanib in metastatic soft tissue sarcoma: a retrospective Turkish oncology group (TOG) study.

AIM: Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). PATIENTS AND METHODS: This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. RESULTS: Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively. CONCLUSION: Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.

FOLFIRINOX versus gemcitabine plus nab-paclitaxel as the first-line chemotherapy in metastatic pancreatic cancer.

Pancreas cancer (PCa) is one of the mortal cancer types with ranking as fourth leading cancer death in both sexes together. FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GNP) are approved as first-line metastatic treatment in PCa. The aim of this study was to compare the clinical outcomes, treated with FFX and GNP as first-line metastatic PCa. Medical records of patients diagnosed with metastatic PCa, from January 2010 to December 2020 were analyzed. This study was a retrospective cohort, multi-institution analysis. The focus of the present study was to compare the efficiency of FFX and GNP chemotherapy combinations in the first-line treatment of PCa. Efficacy had been measured by progression-free survival (PFS) and overall survival (OS). 182 patients diagnosed with PCa receiving metastatic first-line treatment were retrospectively analyzed. Patients were divided into two groups one hundred and three (56.6%) patients treated with FFX and seventy-nine (43.4%) patients treated with GNP. Patients in the FFX group were younger and had a better ECOG performance status. Overall response rate (ORR) was 69.9% in FFX and 37.9% in GNP group (p: 0.000). Disease control rate (DCR) was 73.7% in patients treated with FFX and 39.2% in GNP group (p: 0.000). The median PFS was 8.3 months (FFX 9.1 vs. GNP 6.7, HR = 0.25, 95% CI: 0.16-0.38) the median OS was 12.2 months (FFX 14.1 vs. GNP 9.6, HR = 0.48, 95% CI: 0.31-0.72). Guidelines recommend both FFX and GNP regimens as a first-line treatment of metastatic PCa. In clinical routine, it is still unclear which regiment is more effective. The present study showed increased survival parameters with FFX versus GNP with similar toxicity profiles.

Is the benefit of using adjuvant capecitabine in patients with residual triple-negative breast cancer related to pathological response to neoadjuvant chemotherapy?

BACKGROUND: Triple-negative-breast-cancer (TNBC) has a poor prognosis if pathologic complete response (pCR) cannot be achieved following neoadjuvant chemotherapy (NAC). The group of patients that benefit most from adjuvant capecitabine remains unclear. MATERIALS AND METHODS: We analyzed data of 160 consecutive patients with residual TNBC from eight cancer-center. Pathologic response was defined into two groups as having good-pathologic-response (MillerPayneGrading (MPG) IV-III) or poor-pathologic-response (MPG I-II). The characteristics of patients were compared regarding adjuvant capecitabine usage. RESULTS: Univariate-analysis revealed that age, histology, clinical-stage, tumor-size, lymph-nodes number, menopausal status, and pathological-stage were significantly different between two groups. In multivariate-analysis, menopausal status (p = 0.043) and residual tumor-size (p < 0.001) were found to be independent prognostic factors for pathological response. The hazard-ratio for disease recurrence and death in the poor-response group with adjuvant capecitabine was 2.94 (95% confidence-interval (CI), 1.21 to 7.10; p = 0.016) and 4.080 (95% CI, 1.22 to 13.64; p = 0.022), respectively. DFS (p = 0.58) and OS (p = 0.89) improvements with adjuvant capecitabine were not demonstrated in good-response groups. CONCLUSION: This multicenter-study suggested that only the poor-response group to NAC achieved benefit from adjuvant capecitabine. Postmenopausal status and residual tumor-size were related to poor prognosis.

Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group.

Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience. Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed. Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity. Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial.

Initial Ca 125 Value as a Predictive Marker for High-grade Serous Ovarian Cancer.

OBJECTIVE: To determine the relevance between the cut-off level of cancer antigen 125 (CA 125) level and long-term prognosis in high-grade serous ovarian cancer (HGSCs). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Departments of Oncology, Medeniyet University Goztepe Education and Research Hospital, and Kartal Lutfi Kirdar Education and Research Hospital, Istanbul, Turkey, from January 2017 to June 2019. METHODOLOGY: Medical records of 230 women with HGSC were reviewed randomly from two Oncology Clinics. Descriptive analysis and CA 125 marker levels were evaluated with five years of disease-free survival rate (DFS) and overall survival rate (OS). Patients were divided into groups of high and low initial CA 125 levels (cut-off ≥385U/ml). The ability of initial serum CA 125 levels in predicting the presence of marker-recurrence of ovarian cancer were analysed using ROC (Receiver operating characteristics) curve analysis. RESULTS: Statistically significant predictive value of initial CA 125 level was calculated as 385U/ml (p=0.008). The 5-year DFS of high and low CA 125 levels for all stages in HGSC was statistically significant (p<0.001). The sub-group analysis demonstrated that the significant survival difference was especially in FIGO stage III. Patients with HGSC <385 U/ml had a significantly improved 5-year DFS and OS rates within stage III disease: 5-year DFS (p = 0.008) and 5-year OS (p = 0.004) according to the stratification of CA 125 level. CONCLUSION: Initial CA 125 level appeared to be of beneficial clinical predictive value for HGSC. Key Words: Initial CA 125, Tumor marker, High-grade serous ovarian cancer, Disease-free survival, Overall survival, Predictive value.

Efficacy of abiraterone acetate in castration-resistant metastatic prostate cancer: A real-world data analysis.

PURPOSE: The aim of this study was to evaluate the efficacy of abiraterone in patients with castration-resistant metastatic prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed 51 patients with mCRPC treated with abiraterone acetate from January 2014 to August 2018. Clinicopathological information, treatment modalities, treatment responses, and survival times were retrospectively reviewed. RESULTS: A total of 51 patients who received abiraterone 1000 mg/day + prednisone 10 mg/day between January 2014 and August 2018 were included in the study. Of these patients, 33 (64.7%) had post-chemotherapy (CT) and 18 (35.3%) had CT-naive abiraterone receipt. Median overall survival (OS) was 17.3 months (range 9.3-33.1). Median OS was found to be 12.7 months (range 9.4-18.3) and 29.4 months (range 9.3-33.0) in the CT-naive and post-CT group, respectively (P = .236). Median radiographic PFS (rPFS) was 10.1 months (range 4.5-18.4). In the CT-naive group, rPFS was 10.1 months (IQR 6.0-14.7) and in the post-CT group, it was 9.7 months (range 4.0-18.4) (P = .808). PSA progression-free survival (PSA-PFS) was 9.1 months (range 4.6-13.1). In the CT-naive group, PSA-PFS was 7.4 months (range 4.6-13.4) and in post-CT, it was 9.1 months (range 4.8-13.1) (P = .843). CONCLUSIONS: These results show that abiraterone acetate is an effective and reliable agent in real-life data.

Factors affecting the mortality rate of patients with cancer hospitalized with COVID-19: a single center's experience.

The main objective is to define the mortality of patients with cancer admitted to our hospital, their clinical and demographic characteristics, investigate the risk of COVID-19 for patients with cancer, and determine factors that affect the mortality rates of patients with cancer dying of COVID-19. A total of 2401 patients were admitted to our hospital with the diagnosis of COVID-19 from March 11th, 2020, to May 31st, 2020. Ninety-two out of a total of 112 cancer patients were included in this study based on the planned inclusion/exclusion criteria. The clinical, demographic, and laboratory features and treatments provided were studied, and their effect on mortality rates was analyzed. In our study the median age of the patients was 67 years, and 55.4% were male. More than half (56.5%) of our patients had metastasis. The mortality rate was 6.2% in the overall population with COVID-19, whereas it was 23.9% in patients with cancer. The mortality rate in patients with metastasis was statistically significantly higher compared with those without metastasis (34.0% vs. 10.3% P = 0.008). The mortality rate in patients still smoking was statistically significantly higher than in non-smokers (37.5% vs. 12.5% P = 0.033). The mortality rates of patients with high average C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and D-dimer levels were statistically significantly higher than in those without, and the mortality rates of patients with lower average albumin and hemoglobin levels were statistically significantly higher than those without (P < 0.001, P = 0.006, P = 0.041, P < 0.001, P < 0.001, and P = 0.028, respectively). Having metastases concurrent with COVID-19 was a statistically significant factor predictive of prognosis. Also, high CRP, ferritin, LDH, and D-dimer, and low albumin and hemoglobin were related to increased mortality rates. The predictive and prognostic role of possible factors related to prognosis is still unknown and further large, multicenter prospective studies are needed to confirm these results.

Real-life comparison of the afatinib and first-generation tyrosine kinase inhibitors in nonsmall cell lung cancer harboring EGFR exon 19 deletion: a Turk Oncology Group (TOG) study.

BACKGROUND: The new second-generation tyrosine kinase inhibitors (TKIs) have superior survival outcome and worse toxicity profile when compared with first-generation TKIs according to the results of clinical trials. However, there are limited studies that investigate the efficacy and safety of the new generation TKIs in real-world patients. Thus, we aimed to compare the efficacy and safety of the afatinib, an irreversible inhibitor of ErbB family receptor, and first-generation TKIs in real-world patients. MATERIALS AND METHODS: We included advanced nonsmall cell lung cancer (NSCLC) patients who had EGFR exon 19del mutation and treated with afatinib or first-generation TKIs as upfront treatment between 2016 and 2020. All patient's information was collected retrospectively. The study cohort was divided as afatinib arm and erlotinib/gefitinib arm. RESULTS: A total of 283 patients at the 24 oncology centers were included. The 89 and 193 of whom were treated with afatinib and erlotinib/gefitinib, respectively. After 12.9 months (mo) of follow-up, the median PFS was statistically longer in the afatinib arm than erlotinib/gefitinib arm (19.3 mo vs. 11.9 mo, p: 0.046) and the survival advantage was more profound in younger patients (< 65 years). The 24-mo overall survival rate was 76.1% and 49.5% in the afatinib arm and erlotinib/gefitinib arm, respectively. Although all-grade adverse event (AE) rates were similar between the two arms, grade 3-4 AE rates were higher in the afatinib arm (30.7% vs. 15.2%; p: 0.004). DISCUSSION: In our real-world study, afatinib has superior survival outcomes despite worse toxicity profile as inconsistent with clinical study results and it is the good upfront treatment option for younger patients and elderly patients who have good performance status.

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. OBJECTIVE: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. RESULTS AND LIMITATIONS: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. CONCLUSIONS: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. PATIENT SUMMARY: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.