Search

Systemic treatments (e.g., chemotherapy and targeted therapies) have limited efficacy for patients with locally advanced – unresectable – and metastatic cholangiocarcinoma (CCA), with an overall survival of less than a year. Tumor microenvironment (TME) represents the ecosystem surrounding the tumor which comprises immune cells, fibroblasts, endothelial cells, and a wide range of soluble factors. CCA TME is characterized by an abundant desmoplastic stroma, exhibits a high heterogeneity and it plays a central role in cancer onset and progression. There is growing evidence suggesting that it is possible to target TME in association with other treatment modalities, such as cytotoxic chemotherapy or targeted therapies, paving the way to possible combination strategies with a synergistic effect. Herein, we describe the components of CCA TME – such as cancer-associated fibroblasts and other cells of pivotal importance - with their most relevant interactions, focusing on the preclinical rationale for the development of effective anticancer treatments.

PURPOSEThe purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care.METHODSWe surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes.RESULTSSeven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care.CONCLUSIONThis information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines.

Abstract Background Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory. Methods In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). Results A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR. Conclusions In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition.

Purpose: Complementary and alternative medicine (CAM) has been popular among patients with cancer for several decades. The objectives of this study were to evaluate the prevalence of CAM use and to identify the factors affecting CAM use in a large patient cohort seen at a comprehensive cancer center in Turkey. Patients and Methods: An investigator-designed survey was completed by volunteer patients who visited the outpatient clinic in the medical oncology department. CAM use encompassed pharmacologic agents including vitamins, dietary supplements, and herbal products or nonpharmacologic methods like prayer, meditation, hypnosis, massage, or acupuncture. Results: Of 1,499 patients who answered the survey, 1,433 (96%) used nonpharmacologic CAM and 60 (4%) used pharmacologic CAM (pCAM). The most frequent types of CAM used were prayer (n = 1,433) followed by herbal products (n = 42). pCAM use was not significantly associated with age (P = .63), sex (P = .15), diagnosis (P = .15), or income level (P = .09). However, it was significantly associated with the level of education (P = .0067) and employment status (P < .001). Patients with higher education levels used more pCAM products (P = .025). Among 60 pCAM users, six patients (10%) used pCAM for more than 2 years and 22 (36%) did not consult their physicians about their pCAM use. Only nine patients (15%) reported unpleasant adverse effects related to pCAM. Conclusion: Although CAM use was high among our patients, prevalence of pCAM use was lower than expected. Patients with higher education levels tended to use more pCAM.

Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are a relatively rare, heterogeneous group of diseases in which important advances have been observed in the diagnosis and treatment as well as in our understanding of the biology and genetics of the disease in recent years. Given the insufficient scientific data available on evidence-based management of GEPNETs and the differences in circumstances in individual countries, a multidisciplinary study group was established to provide guidelines for the management of GEPNETS. This study group consisted of a medical oncologist, endocrinologist, surgeon, pathologist, gastroenterologist, and a nuclear medicine specialist, who aimed to prepare a practical guide in the light of existing scientific data and international guidelines, to be used in common clinical practice.

PURPOSE: Colorectal cancer liver metastasis (CRLM) and hepatocellular carcinoma (HCC) are widely treated using microwave and radiofrequency ablation. Local tumor progression (LTP) may develop depending on the shortest vascular distance and large lesion diameter. This study aims to explore the effect of these spatial features and to investigate the correlation between tumor-specific variables and LTP. METHODS: This is a retrospective study covering the period between January 2007 and January 2019. One hundred twenty-five patients (CRLM: HCC: 64:61) with 262 lesions (CRLM: HCC: 142:120) were enrolled. The correlation between LTP and the variables was analyzed using the chi-square test, Fischer’s exact test, or the Fisher-Freeman-Halton test where applicable. The local progression-free survival (Loc-PFS) was analyzed using the Kaplan–Meier method. Univariable and multivariable Cox regression analyses were performed to identify prognostic factors. RESULTS: Significant correlations were observed for LTP in both CRLM and HCC at a lesion diameter of 30–50 mm (P = 0.019 and P < 0.001, respectively) and SVD of ≤3 mm (P < 0.001 for both). No correlation was found between the ablation type and LTP (CRLM: P = 0.141; HCC: P = 0.771). There was no relationship between residue and the ablation type, but a strong correlation with tumor size was observed (P = 0.127 and P < 0.001, respectively). In CRLM, LTP was associated with mutant K-ras and concomitant lung metastasis (P < 0.001 and P = 0.003, respectively). In HCC, a similar correlation was found for Child–Pugh B, serum alpha-fetoprotein (AFP) level of >10 ng/mL, predisposing factors, and moderate histopathological differentiation (P < 0.001, P = 0.008, P = 0.027, and P < 0.001, respectively). In CRLM, SVD of ≤3 mm proved to be the variable with the greatest negative effect on Loc-PFS (P = 0.007), followed by concomitant lung metastasis (P = 0.027). In HCC, a serum AFP level of >10 ng/mL proved to be the variable with the greatest negative effect on Loc-PFS (P = 0.045). CONCLUSION: In addition to the lesions’ spatial features, tumor-specific variables may also have an impact on LTP.

Anemia remains an essential concern affecting the quality of life and the survival of cancer patients. Although there are different approaches to treating anemia in cancer patients, the number of studies reporting the efficacy of iron replacement in cancer patients is limited. In this study, the efficacy and safety of iron carboxymaltose, a parenteral iron treatment option, in the treatment of anemia, were examined retrospectively. A total of 1102 adult patients who received IV ferric carboxymaltose treatment at Hacettepe Oncology Hospital between 2014 and 2020 were included. The mean hemoglobin change observed at the end of the 12th week was 1.8 g/dL, and the rate of patients with an increase in hemoglobin of 1 g/dL or more was 72.1%. It was observed that the treatment demonstrated effectiveness in patients receiving active cancer treatment in all tumor types. The treatment was generally safe, and no grade 3–5 side effects were observed in the patients included in the study. According to one of the most extensive series published in the literature, iron carboxymaltose is an efficient and safe alternative for cancer patients with iron-deficiency anemia.

Background : : Radiofrequency ablation (RFA) or microwave ablation (MWA) is effective for colorectal cancer liver metastases. We aimed to investigate the impact of different variables on survival. Methods : : Sixty-four patients (142 lesions) who underwent thermoablation between January 2007 and January 2019 were retrospectively analyzed. The overall survival (OS) and liver progression-free survival (Li-PFS) were compared using Kaplan-Meier analysis. Univariable and multivariable Cox-regression were done to identify prognostic factors. Results : : No significant difference was found between median OS (59.39 months) and Li-PFS (41.22 months) of patients who received MWA (n = 33); and median OS (61.00 months) and Li-PFS (53.43 months) of patients who received RFA (n = 31) (OS: P = 0.697; Li-PFS: P = 0.122). The median OS and Li-PFS were significantly decreased with lung metastases and K-ras mutations (P < 0.001). There was no correlation between prior systemic chemotherapy (n = 25) and both outcome parameters (OS: P = 0.613; Li-PFS: P = 0.665). No significant difference was observed in patients with lesions less than 30 mm diameter (n = 44) whether they received prior systemic chemotherapy (n = 17) or not (n = 27) (OS: P = 0.27; Li-PFS: P = 0.42). Similarly, in patients with a lesion of 3-5 cm diameter (n = 20; eight of them had prior chemotherapy), there was no correlation for both outcomes (OS: P = 0.069; Li-PFS: P = 0.71). The most important prognostic factor was concomitant lung metastases (hazard ratio = 3.689, P = 0.002). Conclusion : : Concomitant lung metastasis and mutant K-ras were associated with shorter survival. Survival did not differ significantly regarding thermoablation technique or prior systemic chemotherapy. However, in the patient group with lung metastases, curative treatments had better survival than patients who received chemotherapy only. Additional therapeutic options should be considered in patients with concomitant lung metastasis.

Background: Since breast cancer is less common in men than in women, data on the use of new therapeutic agents, including cyclin-dependent kinase 4–6 (CDK 4–6) inhibitors, are limited in patients with metastatic hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) male breast cancer. Therefore; we aimed to investigate the treatment responses of metastatic HR+, HER2-male breast cancer patients treated with CDK 4–6 inhibitors in a multicenter real-life cohort. Methods: Male patients with a diagnosis of HR+ and HER2-metastatic breast cancer, treated with any CDK 4–6 inhibitor, were included in the study. Demographic and clinical characteristics of the patients were recorded. We aimed to determine progression-free survival (PFS) time, response rates and drug related side effects. Results: A total 25 patients from 14 institutions were recruited. The mean age at diagnosis was 57 years. Median follow-up was 19.53 (95% CI: 14.04–25.02) months. The overall response rate was 60%. While the median PFS was 20.6 months in the whole cohort, it wasn't reached in those using CDK 4–6 inhibitors in first line and 10 months in the subsequent lines (p:0.009). No new adverse events were encountered. Conclusion: In our study, we found that CDK 4–6 inhibitors are effective and safe options in men with HR+ and HER2-metastatic breast cancer as in women. Our results support the use of CDK 4–6 inhibitor-based combinations in the first-line treatment of HR+ and HER2-metastatic male breast cancer.

Background: Gastroenteropancreatic neuroendocrine tumors, a heterogeneous group of neoplasms, originates from the neuroendocrine system of the gastrointestinal tract and pancreas. There are limited number of studies investigating neuroendocrine tumors in Turkey. Aims: To define the clinicopathologic, demographic, and survival features of patients with gastroenteropancreatic neuroendocrine tumors. Study Design: A retrospective observational cohort study. Methods: We reviewed hospital records of patients and data was analyzed retrospectively. We investigated the clinical, pathological, survival features, and prognosis of patients with gastroenteropancreatic neuroendocrine tumors (n=128) admitted to the medical oncology department between year 2003 and 2014. Survival estimation was performed by the Kaplan-Meier method. Univariate and multivariate Cox regression models were utilized to investigate the prognostic factors for survival. Results: Of 128 patients with gastroenteropancreatic neuroendocrine tumors, 61 (47.7%) were female and 67 (52.3%) were male. The most common site of the tumor was stomach (36.7%), while the most common stage of tumor at diagnosis was stage 4 (40.9%). The median follow-up period was 37 months, while the 3- and 5-year overall survival rates were 78% and 69%, respectively. The factors significantly affecting overall survival rate were clinical stage, grade, presence of metastasis at diagnosis, and Ki-67 proliferation index. These factors were associated with the 3- and 5-year overall survival rate. Moreover, grade (hazard ratio: 8.34, 95% confidence interval: 2.16-32.22, p=0.01) and presence of metastasis at diagnosis (hazard ratio: 3.18, 95% confidence interval: 1.30-7.77, p=0.01) independently predicted overall survival in multivariate model following adjustment for age and gender. Conclusion: Higher-grade and presence of metastasis at diagnosis are negative independent prognostic indicators of survival in patients with gastroenteropancreatic neuroendocrine tumors.

ObjectivesRegorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC.DesignOpen-label, single-arm, phase IIIb study conducted between July 2013 and April 2015.Setting11 tertiary centres in Turkey.ParticipantsEligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status ≤1. Patients were excluded if they had previously received regorafenib. Of 139 patients screened, 100 were treated and completed the study, and all 100 were analysed. Fifty-eight per cent were male.InterventionsPatients received oral regorafenib, 160 mg once daily, for the first 3 weeks of each 4-week cycle until disease progression, death or unacceptable toxicity.Primary and secondary outcome measuresThe primary endpoint was safety, assessed by incidence of treatment-emergent adverse events (TEAEs). Progression-free survival (PFS) per investigator was the primary efficacy endpoint. There were no secondary endpoints.ResultsThe median treatment duration was 2.5 months (range 0.1 to 20.6). Ninety-six per cent of patients had at least one TEAE and 77% had a grade ≥3 TEAE. The most common grade ≥3 regorafenib-related TEAEs were hypophosphataemia (11%), fatigue (8%), hyperbilirubinaemia (6%), hand–foot skin reaction (5%), hypertension (5%), anorexia (5%) and increased alanine aminotransferase (5%). TEAEs led to dose reduction in 30% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17% of patients. Median PFS was 3.1 months (95% CI 2.9 to 3.8).ConclusionThe regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC.Trial registration numberNCT01853319, ClinicalTrials.gov.

Introduction: Although immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, identifying factors that predict treatment response remains a challenge in clinical practice. There is a need for biomarkers to identify patients who may not benefit from these treatments. It is crucial to identify a simple and cost-effective biomarker that can be easily incorporated into clinical practice. This study aims to investigate the mean platelet volume to lymphocyte ratio (MPVLR), as measured by a hemogram test, and median overall survival (mOS) in patients with cancer treated with nivolumab. Methods: A total of 131 adult patients with metastatic cancer, including malignant melanoma (MM), renal cell carcinoma (RCC), non–small cell lung cancer (NSCLC), and head and neck cancer (HNC), were included in this study. Baseline demographics, ECOG (Eastern Cooperative Oncology Group) performance status, tumor type, and blood count parameters were recorded. Univariate and multivariate analyses were conducted to evaluate potential risk factors. Results: The median age of the patients was 59.87 ± 11.97 years, and the median follow-up period was 20.20 months (IQR, 12.80–27.60). RCC (43.5%) and MM (25.9%) were the most common diagnoses. Patients with ECOG scores of 0–1 had a longer mOS than those with scores of 2–3 (mOS: 20.60 months [95% CI, 14.94–25.29] vs. 5.24 months [95% CI, 0–16.42], p < 0.001). Additionally, patients with lactate dehydrogenase (LDH) levels within the normal range had a longer mOS than those with high LDH levels (mOS: 24.54 months [95% CI, 14.13–34.96] vs. 13.10 months [95% CI, 4.49–21.72], p = 0.038). Patients with low MPVLR also had a longer mOS than those with high MPVLR (mOS: 33.70 months [95% CI, 25.99–41.42] vs. 11.07 months [95% CI, 6.89–15.24], p < 0.001). In the multivariate Cox regression analysis, high MPVLR, ECOG score of 2–3, and high LDH level were associated with shorter mOS (p < 0.001, p = 0.001, and p = 0.046, respectively). Conclusion: This study demonstrates that MPVLR could serve as a novel biomarker for predicting response to nivolumab treatment. Incorporating MPVLR into clinical practice may aid in identifying patients who are less likely to benefit from the treatment.

Background: The albumin levels may potentially be used as a prognostic biomarker in patients with cancertreated with immune checkpoint inhibitors (ICIs) due to its close relationship with nutritional and inflammatory status. However, the available data is limited with heterogeneous patient cohorts, sample sizes and variable cut-offs. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between survival outcomes and albumin levels in patients treated with ICIs.Methods: We conducted a systematic review using the PubMed, Web of Science, and Embase databases to filter the published studies up to 1 June 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model due to the high degree of heterogeneity. The primary outcome measure was hazard ratio (HR) with 95% confidence intervals (CI). The study protocol was registered with the PROSPERO registry (Registration Number: CRD42022337746).Results: Thirty-six studies encompassing 8406 cancer patients with advanced disease were included in the meta-analyses. Almost half of the studies were conducted in NSCLC cohorts (n = 15), and 3.5 gr/dL was the most frequently used albumin cut-off in the included studies (n = 20). Patients with lower albumin levels had a significantly increased risk of death (HR: 1.65, 95% CI: 1.52–1.80, p < 0.0001) than patients with higher albumin levels. Subgroup analyses for study location, sample size, tumor type and albumin cut-off were demonstrated consistent results. Furthermore, in the subgroup analysis of eight studies using albumin levels as a continuous prognostic factor, every 1 gr/dL decrease in albumin levels was associated with significantly increased risk of death by a factor of 10% (HR: 1.10, 95% CI: 1.05–1.16, p = 0.0002). Similar to analyses with overall survival, the patients with lower albumin levels had an increased risk of progression or death compared to patients with higher albumin levels (HR: 1.76, 95% CI: 1.40–2.21, p < 0.001).Conclusion: The available evidence demonstrates that albumin levels may be a prognostic biomarker in advanced cancer patients treated with ICIs. Further research is needed to delineate the role of albumin levels in patients treated with ICIs in the adjuvant setting, as well as the possible benefit of therapeutic approaches to improve hypoalbuminemia.

Abstract Background Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown. Methods A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL. Results Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6th month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42–0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39–0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms. Conclusions Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer. Trial registration This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).

Background: Neovascularization plays a crucial pathogenic role in tumor development and vascular endothelial growth factor (VEGF-A) is a key signaling element that drives angiogenesis, thereby facilitating hepatocellular cancer (HCC) growth and metastasis. We aimed to define the relationship between serum VEGF-A levels and clinical outcomes in a cohort of Turkish patients with HCC. Methods: We enrolled and prospectively followed 84 patients with HCC in our study. Serum VEGF-A levels were measured and we assessed the association between VEGF-A levels and clinical features. Results: Forty-eight patients had cirrhosis while 35 patients were noncirrhotic. Serum VEGF-A levels were significantly lower in HCC patients with cirrhosis compared to non-cirrhotic HCC patients (p = 0.03).In terms of viral hepatitis subtype, 36 (%42.8) of patients were hepatitis B virus (HBV) positive and 8 (%9.5) of patients were hepatitis C virus (HCV) positive. Patients with serum VEGF-A levels ≥100 pg/mL had significantly lower OS rates than patients with serum VEGF-A level