Immunotherapy in the First-Line Treatment of Advanced Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

OBJECTIVES: Data regarding the clinical benefits of immune checkpoint inhibitors (ICIs) are limited in nasopharyngeal carcinoma (NPC). Therefore, we conducted a meta-analysis of phase-III clinical trials to evaluate the benefit of adding ICIs to chemotherapy in the first-line treatment of advanced NPC. METHODS: We conducted a systematic review using Web of Science, PubMed, and Embase for studies published until September 21, 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model. Hazard ratios (HRs) with 95% confidence interval (CI) for progression-free survival (PFS) and overall survival (OS) were the principal summary measures. This protocol was registered in the PROSPERO database (registration number: CRD 42022361866). RESULTS: Three eligible studies with a total of 815 patients were included. The addition of ICIs to standard chemotherapy significantly improved PFS (HR: 0.52, 95% CI: 0.43-0.63, p < 0.0001). Although the OS results were immature, ICIs significantly reduced the risk of death (HR: 0.63, 95% CI: 0.47-0.84, p = 0.0020). The benefit of ICIs was consistent regardless of initial disease presentation (recurrent or de novo), baseline EBV levels, PD-L1 expression, and ECOG performance status. No significant difference in the rates of serious adverse events (HR = 0.98, 95% CI 0.74-1.30) was found between the two groups. CONCLUSION: The available evidence demonstrates that adding ICIs to chemotherapy in the first-line treatment of advanced NPC provided better PFS with acceptable safety. However, a longer follow-up is required to evaluate the true OS benefit of these combinations. LEVEL OF EVIDENCE: NA Laryngoscope, 134:7-17, 2024.

Seven-Year Single-Center Experience of the Efficacy and Safety of Ferric Carboxymaltose in Cancer Patients with Iron-Deficiency Anemia.

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.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

BACKGROUND: We aimed to evaluate the efficacy of fulvestrant and its affecting clinical factors, including the optimal sequencing of fulvestrant and chemotherapy in a real-life cohort. METHODS: The data of 256 metastatic hormone-positive breast cancer patients treated with fulvestrant were evaluated. The association of clinical factors with survival was analyzed with Kaplan-Meier and Cox-regression analyses. RESULTS: The median age of patients was 57 years. More than half of the patients used fulvestrant in later lines and after chemotherapy (75.8%). The median progression-free (PFS) and overall survival (OS) of all cohort were 6.05 ± 0.56 and 29.70 ± 1.61 months, respectively. Primary endocrine resistance (HR: 1.989, 95% CI: 1.430-2.766, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p = 0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p = 0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p = 0.340), disease control rate (p = 0.076), and OS (p = 0.289) and PFS (p = 0.276) were similar to overall cohort. DISCUSSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy.

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil−lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531−17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626−0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.

The efficacy of immune checkpoint inhibitors in rare tumors: A systematic review of published clinical trials.

The immune checkpoint inhibitors (ICIs) entered treatment algorithms in most tumors. However, the data on the efficacy is limited in rare tumors with no phase III studies. We systemically reviewed the clinical trials evaluating the ICI efficacy in rare tumors and included a total of 47 clinical trials in this review. The ICIs demonstrated over 30% response rates in Merkel cell carcinoma and squamous cell carcinoma of the skin and became the standard of care. Additionally, the ICI efficacy was promising in thymic epithelial tumors and gestational trophoblastic neoplasia. In contrast, the ICI efficacy is limited in most sarcomas, germ cell tumors and low-grade neuroendocrine tumors. The ICI efficacy seemed to be improved with combinations targeting tumor microenvironment in sarcomas. The available evidence on ICI efficacy in rare tumors denote a need for better patient selection and novel combination strategies to improve outcomes.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors.

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR's predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100-2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020-1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562-0.747, p= 0.001) and 0.671 (95% CI: 0.598-0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

The association of BMI and sarcopenia with survival in patients with glioblastoma multiforme.

Background: The association between obesity and sarcopenia (via temporal muscle thickness) with overall survival (OS) has been evaluated in several glioblastoma multiforme studies, however, the data are inconclusive. Methods: The authors conducted meta-analyses via the generic inverse-variance method with a random-effects model. Results: In the pooled analysis of five studies, including 973 patients, patients with lower temporal muscle thickness had significantly decreased OS (HR: 1.62, 95% CI: 1.16-2.28, p = 0.005). The pooled analysis of five studies, including 2131 patients, demonstrated decreased OS in patients with lower BMI compared with patients with obesity (HR: 1.45, 95% CI: 1.12-1.88, p = 0.005). Conclusion: Readily available body composition parameters could be used for prognosis prediction and to aid in treatment decisions in patients with glioblastoma multiforme.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

BACKGROUND/AIM: We aimed to evaluate the efficacy of fulvestrant and affecting clinical factors, including the optimal sequencing of fulvestrant and chemotherapy in a real-life cohort. METHODS: The data of 256 metastatic hormone-positive breast cancer patients treated with fulvestrant were evaluated. The association of clinical factors with survival was analyzed with Kaplan-Meier and Cox-regression analyses. RESULTS: The median age of patients was 57 years. More than half of the patients used fulvestrant in later lines and after chemotherapy (75.8%). The median progression-free (PFS) and overall survival (OS) of all cohort were 6.05+/-0.56 and 29.70+/-1.61 months, respectively. Primary endocrine resistance (HR: 1.989, 95% CI: 1.430-2.766, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p=0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p=0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p=0.340), disease control rate (p=0.076), and OS (p=0.289) and PFS (p=0.276) were similar to overall cohort. CONCLUSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

Evaluation of early unplanned readmissions and predisposing factors in an oncology clinic.

BACKGROUND: Unplanned readmission in the first 30 days after discharge is an important medical problem, although the data on cancer patients is limited. So we planned to evaluate the rates and causes of early readmissions and the predisposing factors. METHODS: Patients hospitalized in Hacettepe University Oncology services between August 2018 and July 2019 were included. The demographic features, tumor stages, regular drugs, last laboratory parameters before discharge, and readmissions in the first 30 days after discharge were recorded. The predisposing features were evaluated with univariate and multivariate analyses. RESULTS: A total of 562 hospitalizations were included. The mean age of the patients was 58.5 ± 14.5 years. Almost 2/3 of the hospitalizations were due to symptom palliation and infections. Eighty-three percent of the patients had advanced disease, and over 60% had an ECOG score of 2 and above. In the first 30 days after discharge, 127 patients were readmitted (22.6%). Advanced stage disease, presence of polypharmacy (5 or more regular drugs), hospitalization setting (emergency department (ED) vs. outpatient clinic), and hypoalbuminemia (< 3 gr/dL) were associated with a statistically significant increase in the risk of readmission. Among these factors, advanced-stage disease (HR: 2.847, 95% CI: 1.375-5.895), hospitalization from ED (HR: 1.832, 95% CI: 1.208-2.777), and polypharmacy (HR: 1.782, 95% CI: 1.173-2.706) remained significant in multivariate analyses. CONCLUSIONS: In this study, 22% of cancer patients had early readmissions. The readmission risk increased in patients with advanced disease, hospitalization from ED, and polypharmacy. The optimal post-discharge plan may reduce readmissions in all oncology patients, with priority for these patient groups.