The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review.

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics.

Immune checkpoint inhibitor-related hearing loss: a systematic review and analysis of individual patient data.

PURPOSE: Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies. METHODS: We conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were "hearing loss" OR "hearing impairment" OR "ototoxicity" OR "vestibular toxicity" OR "audiovestibular toxicity" AND "immune checkpoint inhibitor" OR "immunotherapy." RESULTS: A total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively. CONCLUSION: We observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.

Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Optimal adjuvant treatment strategies for TNBC patients with residual disease after neoadjuvant treatment.

INTRODUCTION: The therapeutic armamentarium for the neoadjuvant treatment of triple-negative breast cancer (TNBC) has significantly expanded with the hopes of improving pathological complete response (pCR) rates and the possibility of a cure. However, the data on optimal adjuvant treatment strategies for patients with residual disease after neoadjuvant treatment is limited. AREAS COVERED: We discuss the available data on adjuvant treatment for residual TNBC after neoadjuvant treatment considering clinical trials. Additionally, we discuss ongoing trials to give perspectives on how the field may evolve in the next decade. EXPERT OPINION: The available data support the use of adjuvant capecitabine for all patients and either adjuvant capecitabine or olaparib for patients with germline BRCA1 and BRCA2 mutations, according to availability. The CREATE-X study of capecitabine and OlympiA study of olaparib demonstrated disease-free and overall survival benefits. There is an unmet need for studies comparing these two options for patients with germline BRCA mutations. Further research is needed to delineate the use of immunotherapy in the adjuvant setting, molecular targeted therapy for patients with molecular alterations other than germline BRCA mutation, combinations, and antibody-drug conjugates to further improve outcomes.

Role of sarcopenia on survival and treatment-related toxicity in head and neck cancer: a narrative review of current evidence and future perspectives.

PURPOSE: The purpose of this article is to provide an up-to-date summary of sarcopenia and its clinical implications for patients with head and neck cancer (HNC). METHODS: We conducted a literature review of recent studies investigating the prevalence of sarcopenia in HNC patients, its detection using MRI or CT scans, and its association with clinical outcomes such as disease-free and overall survival time, radiotherapy-related side effects, cisplatin toxicity, and surgical complications. RESULTS: Sarcopenia, characterized by low skeletal muscle mass (SMM), is a prevalent condition in HNC patients and can be effectively detected using routine MRI or CT scans. Low SMM in HNC patients is associated with increased risks of shorter disease-free and overall survival times, as well as radiotherapy-related side effects such as mucositis, dysphagia, and xerostomia. In addition, cisplatin toxicity is more severe in HNC patients with low SMM, leading to higher dose-limiting toxicity and treatment interruptions. Low SMM may also predict higher risks of surgical complications in head and neck surgery. Identifying sarcopenic patients can aid physicians in better riskstratifying HNC patients for therapeutic or nutritional interventions to improve clinical outcomes. CONCLUSIONS: Sarcopenia is a significant concern for HNC patients and can impact their clinical outcomes. Routine MRI or CT scans can effectively detect low SMM in HNC patients. Identifying sarcopenic patients can aid physicians in better risk-stratifying HNC patients for therapeutic or nutritional interventions to improve clinical outcomes. Further research is needed to explore the potential of interventions to mitigate the negative effects of sarcopenia in HNC patients.

Evaluation of sarcopenia as a prognostic biomarker in locally advanced head and neck squamous cell carcinoma.

Background: We aimed to evaluate the effect of sarcopenia on survival in head and neck squamous cell carcinoma patients treated with chemoradiotherapy. Materials & methods: Disease-free survival and overall survival were compared according to cervical computed tomography for radiotherapy in 123 sarcopenic and non-sarcopenic patients with locally advanced head and neck squamous cell carcinoma treated with chemoradiotherapy with weekly cisplatin. Results: In multivariate analyses, pretreatment sarcopenia was associated with lower disease-free survival (hazard ratio: 2.60; 95% CI: 1.38-4.87; p = 0.003) and overall survival (hazard ratio: 2.86; 95% CI: 1.40-5.85; p = 0.004). Sarcopenic patients experienced more frequent radiotherapy-related toxicities and platinum-related side effects than non-sarcopenic patients. Conclusion: Sarcopenia could be a potential biomarker to predict prognosis and treatment toxicity in head and neck squamous cell carcinoma.

Head and neck cancer is one of the main causes of cancer-related death worldwide. Most patients are diagnosed in the advanced stage. Muscle wasting with significant weight loss occurs in nearly half of the patients at the initial diagnosis. In oncology research, sarcopenia has often been described as the loss of skeletal muscle mass. In this study, we evaluated the effect of sarcopenia on survival in head and neck cancer patients. Muscle mass was calculated using information from head and neck computed tomography before radiotherapy treatment in patients. We showed that patients with low muscle mass had significantly worse survival rates and were more susceptible to treatment-related side effects. Sarcopenia may function as a marker showing the course of disease in patients with head and neck cancer.

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 incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.

Prevalence of Common Human Coronaviruses (NL63, 229E, and OC43) in Adults before the COVID-19 Pandemic: a Single-Center Study from Turkey, 2015-2020.

Common Human Coronaviruses (HCoVs), such as NL63, HKU1, 229E, and OC43, induce respiratory tract infections worldwide. Epidemiological studies of HCoVs are of paramount importance because the disease burden and trajectory (in years) have not been well addressed in adults. Here, we aimed to describe the burden of HCoVs in a hospital setting over five years before the coronavirus disease 2019 pandemic. This was a retrospective study of patients (>18 years) between January 1, 2015, and January 1, 2020, whose respiratory specimens were tested by multiplex real-time polymerase chain reaction. In total, 7,861 respiratory samples (4,540 patients) were included, 38% of which tested positive for any respiratory virus. Of these, 212 (12.2%) samples were positive for HCoVs, and their co-infection with other respiratory viruses was 30.6%. Rhinovirus (27.6%) was the most common co-infection among all three HCoVs. The overall prevalence of HCoVs tended to be the highest in the winter (40.9%). Patients aged ≥60 years had the highest prevalence of overall HCoVs (39.7%). Given the duration and large sample size, this study from Turkey is one of the largest to date among adults in the literature. These epidemiological data and molecular surveillance of HCoVs have important implications for the control and prevention of respiratory infections.

The association between pan-immune-inflammation value and survival in head and neck squamous cell carcinoma.

PURPOSE: A significant portion of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) relapse despite multimodality treatment denoting the need for biomarkers. The pan-immune-inflammation value (PIV) is a recently developed blood count-based prognostic biomarker. We evaluated the relationship between PIV and survival in locally advanced HNSCC patients treated with chemoradiotherapy (CRT). METHODS: A total of 199 patients who underwent CRT at Hacettepe University Oncology Hospital were included. The relationship between clinical and laboratory parameters with overall survival (OS) and disease-free survival (DFS) was analyzed by multivariate analyses. RESULTS: The median age was 59 years and 90.5% of the patients were male. 66.8% of the patients had laryngeal primaries, and 78.9% had T3-T4 disease. 84.9% of the patients received CRT with cisplatin. The optimal PIV threshold value was calculated as 404 in ROC analyses. This PIV value had 75.8% sensitivity and 70.4% specificity for OS prediction (AUC 0.781; 95% CI 0.715-0.846; p < 0.001). In multivariate analyses, high PIV levels (≤ 404 vs. > 404, HR 2.862; 95% CI 1.553-5.276; p = 0.001), higher NLR (≤ 2.5 vs. > 2.5, HR 1.827; 95% CI 1.017-3.281; p = 0.044) levels and ECOG performance score of 2 (HR 2.267; 95% CI 1.385-3.711; p = 0.001) were associated with shorter OS. These factors were associated with shorter DFS also (HR for PIV 2.485, 95% CI 1.383-4.467, p = 0.002). CONCLUSIONS: We observed shorter OS and DFS in locally advanced HNSCC patients with high PIV levels. If prospective studies support our findings, the PIV score could be a prognostic biomarker in HNSCC.

Immunogenicity of two doses of inactive COVID-19 vaccine and third booster dose mRNA vaccine in patients with cancer receiving active systemic therapy.

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 µg/ml [IQR 0-1.17 µg/ml] vs median 0.91 µg/ml [IQR 0-2.24 µg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 µg/ml [IQR 0-1.17 µg/ml] after two doses vs 12.6 µg/ml [IQR 1.8-69.1 µg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.

The benefit of treatment beyond progression with immune checkpoint inhibitors: a multi-center retrospective cohort study.

OBJECTIVE: Treatment beyond progression (TBP) with immune checkpoint inhibitors (ICIs) is an evolving field due to the limitations of conventional imaging in response evaluation. However, real-life data on the benefit of TBP is scarce, especially from the limited resource settings and patients treated in the later lines. Therefore, we aimed to investigate the survival benefit of TBP with ICIs in patients with advanced tumors from a limited resource setting. METHODS: For this multi-center retrospective cohort study, we included 282 patients treated with ICIs and had radiological progression according to RECIST 1.1 criteria. We evaluated post-progression survival according to the use of TBP (TBP and non-TBP groups) with univariate and multivariate analyses. RESULTS: The cohort's median age was 61, and 84.4% were treated in the second or later lines. 82 (29.1%) of 282 patients continued on ICIs following the initial progression. In multivariate analyses, patients in the TBP group had improved post-progression survival compared to non-TBP (13.18 vs. 4.63 months, HR: 0.500, 95% CI: 0.349-0.717, p < 0.001). The benefit of the TBP was independent of the tumor type, treatment line, and age. Furthermore, TBP with ICIs remained associated with improved post-progression survival (HR: 0.600, 95% CI: 0.380-0.947, p = 0.028) after excluding the patients with no further treatment after progression in the non-TBP arm. CONCLUSIONS: In this study, we observed that patients receiving ICIs beyond progression had considerably longer survival. Continuation of ICIs after progression should be considered a reasonable management option for patients with advanced cancer, specifically for patients with limited alternative options.

The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

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.

The benefit of immunotherapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

Background: A systemic review of the survival benefit of immune checkpoint inhibitors (ICIs) in phase III hepatocellular carcinoma (HCC) trials was conducted. Methods: Meta-analyses were performed with the generic inverse-variance method with a fixed-effects model. Results: In 10 trials encompassing 6123 patients, ICI-based therapy (monotherapy/combination) improved overall survival (OS) compared with the control arm (hazard ratio [HR]: 0.77; 95% CI: 0.70-0.84; p < 0.001). The survival benefit was consistent across variable treatment lines, Eastern Cooperative Oncology Group performance status and AFP levels. While the OS benefit was more pronounced in hepatitis B-related HCC (HR: 0.70; 95% CI: 0.63-0.77; p < 0.001), OS was improved in hepatitis C-related (HR: 0.83; 95% CI: 0.71-0.98) and nonviral HCC (HR: 0.86; 95% CI: 0.77-0.97). Conclusion: ICI-based therapies should be the standard for all patients with advanced HCC.

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.

Behçet's Disease-related Budd-Chiari Syndrome Successfully Managed with anti-TNF Antibody: A Case Report and Review of the Literature.

Behçet's disease (BD) is multisystemic vasculitis with heterogeneous clinical manifestations. We describe the case of a 26-year-old man who presented with Budd-Chiari syndrome (BCS) related to BD. The patient received infliximab (IFX) due to the severity of vascular involvement. Subsequently, after IFX therapy, hospital-acquired pneumonia, trapped lung, and fungal infection of the lung and central nervous system developed as complications. The patient benefited from a second course of IFX and clinical remission was achieved following early identification and treatment of complications. Data on the presentation and prognosis of BCS related to BD are extremely limited. Our case report supports the growing evidence that anti-TNF antibody is a promising treatment for BD-related BCS. LEARNING POINTS: Behçet's disease-related Budd-Chiari syndrome is a rare form of vascular involvement that severely affects mortality.Behçet's disease-related Budd-Chiari syndrome is frequently confused with idiopathic thrombosis and may be underdiagnosed.Infliximab could be a therapeutic option for refractory Behçet's disease with major vascular involvement, but the increased risk of opportunistic infections should be kept in mind.

Infectious complications of cyclin-dependent kinases 4 and 6 inhibitors in patients with hormone-receptor-positive metastatic breast cancer: a systematic review and meta-analysis.

AIM: The combination of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors plus endocrine therapy (ET) improved the survival outcomes and became the standard of care in the treatment of metastatic hormone-positive breast cancer. However, these combinations increased the risk of neutropenia compared with ET alone. While the infection-related mortalities did not seem to be increased, the exact risk of infections with CDK 4/6 inhibitor and ET combinations is relatively understudied. Therefore, we performed a meta-analysis of CDK 4/6 inhibitor clinical trials to assess the infection risk of adding CDK4/6 inhibitors to ET. MATERIAL AND METHOD: We systemically searched the PubMed database for relevant clinical trials. For each study, all grade and grade 3 or higher infections, upper respiratory tract infections (URTI), urinary tract infections (UTI), pneumonia, and febrile neutropenia rates were recorded whenever available. The hazard ratios (HR) with a 95% confidence interval (CI) of infection risk were calculated via the generic inverse-variance method with a random-effects model. RESULTS: Nine eligible studies were included in the analyses (MONALEESA-2,3,7, MONARCH-2,3, MONARCH plus, PALOMA-1,2,3). In the meta-analysis of these studies, CDK 4/6 inhibitors plus ET arms were associated with increased all grade infections (HR 1.77, 95% CI 1.56-2.01, p < 0.00001), grade 3 or higher infections, (HR 1.77, 95% CI 1.28-2.43, p = 0.0005), UTIs (HR 1.59, 95% CI 1.19-2.12, p = 0.002), and febrile neutropenia (HR 4.28, 95% CI 1.73-10.62, p = 0.002). CONCLUSION: In this meta-analysis, we observed that adding CDK4/6 inhibitors to ET significantly increased the risk of all grade, grade 3 or higher infections, and urinary tract infections. We propose that closer follow-up for infections should be considered for metastatic breast cancer patients using CDK 4/6 inhibitors. This may help clinicians to recognize infections earlier which prevents early death from infection.

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.

Relative Vaccine Effectiveness of the Third Dose of CoronaVac or BNT162b2 Following a Two-Dose CoronaVac Regimen: A Prospective Observational Cohort Study from an Adult Vaccine Center in Turkey.

Coronavirus disease 2019 (COVID-19) continues to pose a threat to public health with the potential for the emergence of new variants. Vaccines are the milestones to control and slow down the damage of the pandemic. As of January 2021, a two-dose regimen with CoronaVac was authorized in Turkey. Due to the waning seroprevalence rate of SARS-CoV-2 over time, BNT162b2 or CoronaVac has been administered as the third dose following a two-dose CoronaVac regimen as a national vaccination policy. As of 14 January 2021, 5243 volunteers who received two doses of the CoronaVac vaccine at Hacettepe University Adult Vaccine Center were followed prospectively. In our study, relative vaccine effectiveness (VEff) for the third dose of the CoronaVac was 58.24% and 87.27% for BNT162b2 in preventing symptomatic COVID-19 cases. There were no hospitalizations, intensive care unit admissions, or deaths in third-dose booster groups with either BNT162b2 or CoronaVac, yielding 100% effectiveness. Both homologous or heterologous third-dose boosters provided further protection against severe COVID-19 and should be prioritized as an effective strategy to combat the COVID-19 pandemic.