Prognostic Value of Inflammation And Nutrition-Based Scores in Non-Small Cell Lung Cancer.

OBJECTIVE: In studies conducted on non-small cell lung cancer (NSCLC) patients, many factors such as age, stage, weight loss, lymph node, and pleural involvement have been shown to affect survival. On the other hand, systemic inflammation plays a critical role in proliferation, migration, invasion, and metastasis. Inflammation and nutrition-based prognostic scores are reported to be associated with survival in patients with NSCLC. The aim of our study is to show the effects of these scores on survival and disease progression in NSCLC patients. SUBJECTS AND METHODS: Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) values in 102 patients with stage 1,2 and 3A NSCLC were analyzed retrospectively. RESULTS: NLR (p < 0.001), PLR (p = 0.001), PNI (p < 0.001), and mGPS (p = 0.001) variables showed a statistically significant difference according to mortality groups. NLR and PLR values were higher in exitus patients. However, PNI values were higher in surviving patients. NLR (p < 0.001), PLR (p = 0.004), PNI (p = 0.001), and mGPS (p = 0.015) variables showed a statistically significant difference in terms of locoregional recurrence. PNI (p = 0.001) and mGPS (p = 0.001) in terms of distant metastasis development during follow-up and treatment, showed a statistically significant difference. CONCLUSION: NLR, PLR, PNI, and mGPS are easily accessible and non-invasive parameters and provide predictive information about survival and disease course. We showed the effect of these parameters on the prognosis.

The safety and efficacy of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter real-world study from Turkey.

The aim of the study was to evaluate the real-world clinical outcomes of atezolizumab and bevacizumab (Atez/Bev) as the initial therapy for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 65 patients treated with Atez/Bev for advanced HCC from 22 institutions in Turkey between September 2020 and March 2023. Responses were evaluated by RECIST v1.1 criteria. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox regression model was employed to conduct multivariate analyses. The median age was 65 (range, 22-89) years, and 83.1% of the patients were male. A total of 1.5% achieved a complete response, 35.4% had a partial response, 36.9% had stable disease, and 26.2% had progressive disease. The disease control rate was 73.8% and associated with alpha-fetoprotein levels at diagnosis and concomitant antibiotic use. The incidence rates of any grade and grade ≥ 3 adverse events were 29.2% and 10.7%, respectively. At a median follow-up of 11.3 (3.4-33.3) months, the median PFS and OS were 5.1 (95% CI: 3-7.3) and 18.1 (95% CI: 6.2-29.9) months, respectively. In univariate analyses, ECOG-PS ≥ 1 (relative to 0), Child-Pugh class B (relative to A), neutrophil-to-lymphocyte ratio (NLR) > 2.9 (relative to ≤ 2.9), and concomitant antibiotic use significantly increased the overall risk of mortality. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 2.69, P = .02), NLR > 2.9 (HR: 2.94, P = .017), and concomitant antibiotic use (HR: 4.18, P = .003) were independent predictors of OS. Atez/Bev is an effective and safe first-line therapy for advanced-stage HCC in a real-world setting. The survival benefit was especially promising in patients with a ECOG-PS score of 0, Child-Pugh class A, lower NLR, and patients who were not exposed to antibiotics during the treatment.

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

The Prognostic Role of Mismatch Repair Status and CDX-2 Expression with Inflammatory Markers and Pathological Risk Factors in Stage II and III Colon Cancer: Multicenter Real-Life Data.

OBJECTIVE: Colorectal cancer is common worldwide, and adjuvant treatment's benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer. METHODS: A total of 226 stage II/III colon cancer patients with a median age of 59 years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis. RESULTS: One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [p < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03-0.17, p < 0.001 HR: 1.7, CI 95% 1.1-3.0, p = 0.03], disease stage [HR:2.6, CI 95% 1.43-4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18-785, p < 0.001 were independent significant prognostic factors for DFS. CONCLUSION: CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

The impact of adjuvant oxaliplatin and tumor sidedness on the overall survival of stage IIB colon cancer patients: a multicentre study.

The aim of this multicentre retrospective study was to compare the efficacy of adjuvant chemotherapy regimens both with and without oxaliplatin and tumor sidedness in stage IIB (pT4aN0) colon cancer patients. This study included patients with stage IIB colon cancer who underwent curative surgery and received adjuvant chemotherapy. The patients were divided into two groups (one with and one without oxaliplatin) to compare the overall survival (OS) in right- and left-sided tumors. The study population included 298 patients with stage IIB colon cancer (median age: 57) of whom 69.1% were male. Forty-four per cent of these patients (n = 131) were diagnosed with right-sided colon cancer. The median follow-up duration was 35.9 months. In the entire population, a median OS was not reached, and the five-year OS was 83%. The median disease-free survival (DFS) was 12 months. There was no significant difference in terms of the five-year OS between right- (82%) and left-sided (84%) colon tumors (p = 0.67). In addition, the five-year OS of patients treated with and without oxaliplatin were 76% and 89%, respectively, and there was no statistically significant difference (p = 0.23). The five-year OS of the patients treated with and without oxaliplatin were 83% and 96.5%, respectively, (p = 0.8) in right-sided colon tumors, while it was 75% and 93% (p = 0.06), respectively, in left-sided colon tumors. Tumor sidedness and the addition of oxaliplatin to adjuvant chemotherapy were not found to be associated with the OS in stage IIB colon cancer patients in our study. Further large prospective studies that also include MSI, RAS and BRAF status data are warranted in colon cancer patients.

A new biomarker for lung metastasis in non-seminomatous testicular cancer: De Ritis Ratio.

PURPOSE: We aimed to show that the De Ritis Ratio (DRR) may be a new biomarker for lung metastasis in non-seminomatous Testicular Cancers (TC). MATERIAL AND METHODS: Patients who underwent radical orchiectomy due to TC between January 2010 and January 2021 were included in the study. Demographic characteristics, preoperative laboratory and radiological findings and pathological data of the patients were recorded. The DRR was calculated from preoperative peripheral blood analysis. RESULTS: A total of 124 patients with non-seminomatous TC were included. Mean patient age was 30.67±7.45 years, and the mean tumour diameter was 4.69±2.55 cm. 61 patients had T1, 51 had T2, and 12 had T3 disease. 42 of them had lung metastasis; 82 of them had no lung metastasis. The optimal DRR threshold was 1.21 for lung metastasis. [Area Under the Curve (AUC): 0.724 with a sensitivity of 81% and specificity of 74%]. DRR was determined as an independent prognostic factor for lung metastasis in univariate and multivariate analyses (p=0.002). CONCLUSIONS: A high preoperative DRR can be used to detect the presence of lung metastases in non-seminomatous TCs.

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.

Effect of Adjuvant Chemotherapy in Stage III Cervical Cancer Patients Treated with Concurrent Chemoradiation: A Multicenter Study.

INTRODUCTION: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. METHODS: We performed a multicenter, retrospective analysis of 139 International Federation of Gynecology and Obstetrics stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. RESULTS: Five-year progression-free survival (PFS) was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p = 0.008). Median PFS was 30.9 months (CI 95% 14.8-46.9) and 16.6 months (CI 95% 9.3-23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival (OS) was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p < 0.001). Median OS was 132.2 months (CI 95, %66.5-197.8) and 34.9 months (CI 95% 23.1-46.7) in patients receiving CCRT with and without AC, respectively. CONCLUSION: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC.

Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer.

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.

Survival and Prognostic Factors in Limited-stage Small-cell Lung Cancer.

OBJECTIVE: To evaluate the factors affecting overall survival (OS) and progression-free survival (PFS) in patients with limited stage-small cell lung cancer (LS-SCLC). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Prof. Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey from January 2002 to October 2019. METHODOLOGY: Data of 89 patients was analysed, who were treated with chemoradiotherapy (CRT) for LS-SCLC, of whom some had also received prophylactic cranial irradiation (PCI). The clinical course and survival rates of LS-SCLS patients treated with different treatment modalities, were evaluated and the prognostic factors were analysed by Cox-regression analysis. RESULTS: The median age of the patients was 59.6 (39 - 83) years-old; 82% were men. The median follow-up duration was 20 (1 - 189) months. The median PFS and OS were 16 (95% CI, 13-18) months and 33 (95% CI, 25-41) months. Patients, who underwent PCI had better OS compared to patients who did not [54 (95% CI, 27-87) months vs. 19 (95% Cl,, 13-25) months, log-rank, p = 0.004]. Grade 3-4 hematologic toxicities were observed in 12 (13.5%) patients and grade 3-4 esophagitis was observed in 25 (28.1%) patients. Younger age, ECOG 0-1, stage I-II disease, complete response to CRT were good prognostic factors on OS and PFS. A complete response to  CRT was also a good independent factor in terms of PFS and OS. CONCLUSION: In this study, younger age, better ECOG status, stage I-II disease, and complete response to CRT had a favourable impact on OS and PFS in LS-SCLC. In addition, PCI has been shown to increase survival in these patients. Key Words: Limited-stage, Small-cell lung cancer, Thoracic radiotherapy, Chemoradiotherapy.

Can 68Ga-PSMA PET/CT-derived prostate-specific membrane antigen expression parameters predict prostate-specific antigen response to enzalutamide treatment?

OBJECTIVE: In patients with metastatic castration-resistant prostate cancer (mCRPCa), enzalutamide is administered when docetaxel treatment fails. The purpose of the study was to evaluate the relationship between prostate-specific antigen (PSA) response and metabolic parameters obtained from 68Ga-PSMA PET/CT before treatment in this patient group. METHODS: From February 2018 to May 2020, 34 patients with mCRPCa were enrolled in this study. The association between PSA response (at least 50% decrease compared to the pretreatment value) and quantitative prostate-specific membrane antigen (PSMA) expression parameters such as SUVmax, SUVmean, PSMA-TV (PSMA receptor-expressing tumor volume) and TL-PSMA (total lesion PSMA receptor expression) were evaluated. RESULTS: Mean SUVmax, SUVmean, PSMA receptor-expressing tumor volume (PSMA-TV) and total lesion PSMA receptor expression (TL-PSMA) values were 33.66 ± 20.42; 8.82 ± 5.03; 319.85 ± 615.12 cm3; and 2894.76 ± 5195.13, respectively. In the posttreatment 12th week, 22 patients (64.7%) had PSA response, while 12 patients (35.3%) were nonresponders. In patients with PSA response, PSMA-TV values were significantly lower than nonresponders (78.37 ± 80.99 cm3 vs. 451.58 ± 734.61 cm3; P = 0.028). But there was no significant difference between responders and nonresponders in terms of age, ISUP grade, SUVmax, SUVmean, TL-PSMA, pretreatment PSA values, presence of local recurrence or metastases at any site. CONCLUSION: PSMA-TV values on 68Ga-PSMA PET/CT imaging before starting enzalutamide treatment following docetaxel failure can predict PSA response in patients with mCRPCa.

Anakinra treatment in patients with familial Mediterranean fever: a single-centre experience.

OBJECTIVES: Anakinra is proven to be effective in controlled trials in terms of attack frequency and subclinical inflammation in colchicine-resistant patients. The objective of this study was to review the patients followed in our single centre with FMF who received anakinra because of insufficient colchicine response. METHODS: The study was conducted at a tertiary rheumatology centre experienced in autoinflammatory diseases. The patients were treated for at least 1 month with anakinra. Patients with amyloidosis and pregnancy were not included. Attack frequency, patient global assessment scales of disease severity and acute phase reactants were recorded before and throughout anakinra treatment. Criteria of treatment termination were side effects, disease remission, inadequate response, pregnancy plan and non-compliance. RESULTS: One hundred and six patients diagnosed with FMF were treated with anakinra; 45.92% of the patients had a homozygous M694V mutation; 83 of the 98 patients tested for MEFV carried at least one copy of M694V. Attack frequency decreased while on anakinra treatment; in fact, no attacks were observed in 75 patients. Visual analogue scale score decreased from 7.49 (2.03) to 3.08 (2.82) (P = 0.001). Currently, 71 patients are still on anakinra treatment. Treatment of 34 patients was discontinued (32%). Insufficient response and side effects were the most common reasons for treatment discontinuation. All of the side effects observed were reversible and the patients alleviated after treatment cessation. In four patients, leukopenia was observed. CONCLUSION: In patients who were refractory to colchicine, anti-IL-1 agent anakinra was shown to be effective and safe. The effectiveness of anakinra stems from preventing attacks and increasing the quality of life.

Safety and efficacy of anti-interleukin-1 treatment in 40 patients, followed in a single centre, with AA amyloidosis secondary to familial Mediterranean fever.

OBJECTIVE: The main devastating complication of FMF is AA amyloidosis. Approximately 10-15% of the patients are either intolerant or have an insufficient response to colchicine treatment. The most promising alternative treatment approach is anti-IL-1 agents. The aim of this study was to evaluate the efficacy and safety of anti-IL-1 therapy in FMF amyloidosis. METHODS: Forty-four patients with amyloidosis who had been treated with anti-IL-1 agents, anakinra and/or canakinumab, were assessed retrospectively for efficacy and safety. Five patients were on haemodialysis and four had received a renal transplant. RESULTS: The mean duration of anti-IL-1 treatment was 21.4 (18) months. Among 35 patients who were not on dialysis, renal function was maintained or improved in 79.4% but deteriorated in 20.6%. Patients with creatinine levels below 1.5 mg/dl at onset benefitted more from IL-1 inhibition with regard to their kidney functions and acute phase reactants. No additional side effects were observed in patients with renal replacement treatments. The major side effect of anakinra was injection-site reaction observed in four patients. CONCLUSION: Anti-IL-1 agents are well tolerated and effective in the treatment of amyloidosis secondary to FMF, including patients on dialysis and renal transplant recipients. This approach may improve the lifespan of transplanted kidneys in FMF patients.