Sixth-Week Immune-Nutritional-Inflammatory Biomarkers: Can They Predict Clinical Outcomes in Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors?

BACKGROUND: We investigated the relationships between inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Lung Immune Prognostic Index (LIPI), and modified Glasgow prognostic score (mGPS) to determine whether they could predict treatment response to pembrolizumab or nivolumab (immunotherapy) 6 weeks after the start of treatment (post-treatment). METHODS: We included all patients with lung cancer treated with immunotherapy. We examined the biomarker trends and explored their associations with progression-free survival (PFS), overall survival (OS), and response rate (RR) at 6 weeks. RESULTS: Eighty-three patients were enrolled in the study. The presence of liver metastasis, low post-treatment NLR (<5), low post-treatment PLR (<170), intermediate post-treatment LIPI, and immune-related adverse events were significantly associated with the response. The multivariate analysis revealed that high post-treatment NLRs ≥ 5 (p = 0.004) and PLRs ≥ 170 (p ≤ 0.001) were independent prognostic factors of shorter OS. A good LIPI status was associated with better PFS (p = 0.020) and OS (p = 0.065). Post-treatment mGPS (0-2) was significantly associated with improved PFS (p = 0.009) and OS (p = 0.064). CONCLUSIONS: Post-treatment NLR, PLR, LIPI, and mGPS are associated with worse OS and recurrence. These findings should be independently and prospectively validated in further studies.

A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey.

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases.

Development of a Novel Predictive-Prognostic Scoring Index for Immune Checkpoint Inhibitors in Advanced Non-small Cell Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of patients with driver mutation absent advanced non-small cell lung cancer (NSCLC). The present study aimed to develop a reliable, reproducible, and practical scoring system to prognosticate and predict response to ICI response in patients with advanced NSCLC. PATIENTS AND METHODS: All patients who were diagnosed as having unresectable/advanced stage NSCLC and were treated with at least one cycle of ICIs at the Medical Oncology Departments of Dr. Burhan Nalbantoglu State Hospital (Nicosia, Cyprus) and Near East University Hospital (Nicosia, Cyprus) were included in the study. The association between variables and OS was evaluated using a Cox proportional hazards regression model. Variables with a P-value less than 0.05 in the univariate analysis were included in the multivariate model. A prognostic scoring system was developed.  Survival estimates were calculated using the Kaplan-Meier method. The value of the Concordance index (C-index) and the area under the curve (AUC) was used to evaluate the discriminative ability of scoring systems. RESULTS: One hundred fifty consecutive patients with unresectable/metastatic NSCLC who received PD-1 inhibitors between March 2017 and November 2022 were included. In the multivariate Cox regression model, serum lactate dehydrogenase (LDH), C-reactive protein (CRP) levels, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) were significantly associated with OS. We generated a new score using CRP ³1.0 mg/dL, ECOG PS ³2, and LDH level >ULN. Relative weight was based on the HRs of multivariate analyses (CRP ³1.0 mg/dL 2 points, ECOG PS ³2 2.5 points, and LDH level >ULN 1.5 points). The cohort was divided into three risk groups based on the sum of factors present: 0-2.5 (good risk), 3.5-4.5 (intermediate risk), or 6 (poor risk). The median OS was 18.9, 7.4, and 2.9 months for good, intermediate, and poor risk categories, respectively (log-rank test, p<0.001). The Harrell C-index of CEL to predict OS and PFS was 0.73 and 0.69, respectively, indicating significant predictability. The AUC of the scoring index for predicting the responses was 0.765 (95% CI: 0.685-0.845). CONCLUSION: The CEL score is a promising prognostic and predictive index consisting of serum CRP levels (C), ECOG PS (E), and serum LDH levels (L). This represents another step forward in the treatment of patients with advanced NSCLC.

Prognostic value of pretreatment immune inflammation indices in patients with immune-related tumors.

BACKGROUND: Pretreatment high levels of lactate dehydrogenase (LDH), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), modified Glasgow prognostic scores (mGPS), prognostic nutritional index (PNI), and other prognostic biomarkers have been associated with poor overall survival (OS) in immune-related tumor types. Therefore, we explored a simple, inexpensive and effective method for cancer prognosis. METHODS: Between March 2017 and June 2022, 111 individuals who had immunotherapy were retrospectively examined. Oncologic outcomes of patients with immune-related tumor types, include OS and progression-free survival (PFS), and response rates (RR). RESULTS: Pretreatment ECOG (Eastern Cooperative Oncology Group) performance quality was independently linked with poor OS ECOG ≥2 (HR 4.80, 95% CI 2.57-8.96, p < .001) and inferior PFS (HR 3.31, 95% CI 2.023-5.445, p < .001). Additionally, a high LDH status prior to therapy was independently linked to an inferior OS (HR 1.004, 95% CI 1.001-1.007, p = .003) and inferior PFS (HR 1.004, 95% CI 1.002-1.006, p < .001). Higher MLR at baseline was a prognostic factor for both shorter PFS (HR = 3.691, 95% CI 1.582-8.610, p = .003) and OS (HR = 2.876, 95% CI 1.127-7.342, p = .027). CONCLUSIONS: In our cohort, elevated pre-treatment MLR, LDH and ECOG ≥2 were associated with poor OS and PFS. Prospective studies need to determine the utility of them.

Salvage chemotherapy in patients with nonsmall cell lung cancer after prior immunotherapy: a retrospective, real-life experience study.

Patients with advanced nonsmall cell lung cancer (NSCLC) who progress with immune checkpoint inhibitors (ICIs), salvage chemotherapy remains the only viable option for tumors that do not harbor genomic alterations. Data on the efficacy of salvage chemotherapy after immunotherapy (SCAI) are scarce. Our main objective in the current study was to evaluate the efficacy of SCAI. All consecutive patients who were diagnosed as having metastatic NSCLC and received at least one dose of ICIs were retrospectively reviewed. We computed progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) with SCAI. We also analyzed associations between survival and various clinicopathologic factors. We identified 35 patients with advanced NSCLC who received at least one dose of SCAI. The median age was 66 years. Most of patients were male ( n = 26, 74.3%) and former or current smokers ( n = 33, 94.3%). The majority of the patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 ( n = 22; 62.9%), and there were no patients with driver mutations. SCAI was administered as second-line therapy in 21 (60.0%) patients and third-line in 14 (40.0%) patients. The ORR to SCAI was 20.0% with median PFS and OS were 2.43 (95% CI, 1.69-3.16) months and 4.40 (95% CI, 2.17-6.62) months, respectively. In multivariate analysis, ECOG PS 2 was confirmed as being independently associated with inferior OS. We demonstrated that patients with NSCLC who progressed to ICIs had limited clinical benefit with salvage chemotherapy, particularly for patients who were ECOG PS 2.

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

Adjuvant treatment with paclitaxel plus trastuzumab for node-negative breast cancer: real-life experience.

Background: In node-negative HER2-overexpressed breast cancers, adjuvant paclitaxel plus trastuzumab treatment is a successful de-escalation approach with excellent survival outcomes. Methods: All patients with HER2+ breast cancer treated in our centers were retrospectively reviewed. Results: We analyzed 173 patients who were treated with adjuvant paclitaxel plus trastuzumab. The mean tumor size was 2.2 cm. There were eight invasive disease events or death: four distant recurrences (2.3%), three locoregional recurrences (1.7%) and one death without documented recurrence after a 52 month follow-up. The 3-year disease-free survival and recurrence-free interval rate was 96.6%. Conclusion: This real-life experience with adjuvant paclitaxel plus trastuzumab demonstrated few distant recurrences and is compatible with the APT trial findings.

Lay abstract In oncology practice, there have been some efforts to avoid the toxicity of combination chemotherapies and reduce the amount of treatment given in recent decades. These strategies have been studied especially for patients with a specific subtype of early-stage breast cancer. We present the results from patients treated in our centers and discuss them in relation to the literature.

First-line pembrolizumab efficacy in patients with advanced non-small cell lung cancer: A Bi-center retrospective, real-life experience study.

PURPOSE: Immune checkpoint inhibitors (ICIs) have caused a paradigm shift in the treatment landscape of advanced non-small cell lung cancer (NSCLC). Real-world practice may be different from randomized studies. The purpose of this study was to investigate the real-world pembrolizumab efficacy with or without chemotherapy. METHODS: All consecutive patients aged over 18 years who were diagnosed as metastatic NSCLC and received at least one dose of first-line pembrolizumab treatment were retrospectively reviewed. The patients hadn't received no previous systemic therapy. RESULTS: A total of 44 patients treated with pembrolizumab were enrolled. Just over half (51.2%) of the patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, and 36.4% had liver metastasis. There were no patients with driver mutations, 18.2% had programmed death ligand-1 (PD-L1) 50% expression and 82.3% were treated with pembrolizumab plus chemotherapy. The median progression-free survival (PFS) and overall survival (OS) were 3.0 months (95% CI: 0.9-5.0 months) and 6.6 months (95% CI: 0.7-12.4 months), respectively. Multivariate analysis identified liver metastasis and adrenal metastasis as independent predictors of OS. CONCLUSIONS: PFS, OS, objective response and disease control rate results were significantly worse than in randomized studies. ICIs are not an infallible treatment option to be used for every patient with advanced NSCLC encountered in daily clinical practice. Attention should be payed to stringent eligibility criteria used in randomized studies as much as possible and try to manage patients according to these criteria.

The role of the pharmacist in improving medication beliefs and adherence in cancer patients.

BACKGROUND: Multiple factors have been reported to affect adherence to medication, including beliefs about medicines, while specifically tailored pharmaceutical care services for patients may improve adherence. The aim was to assess the impact of counselling by an oncology pharmacist on patients' medication adherence and beliefs. METHODS: An interventional prospective study was performed in the oncology department at a tertiary hospital in Northern Cyprus from November 2017 to April 2018. The Beliefs about Medicines Questionnaire was used to evaluate the balance between beliefs about necessity and concerns and medication beliefs before and after an educational intervention. The Morisky Green Levine Test 2018 was used to evaluate adherence. RESULTS: In total, 81 patients (65.4% females; mean age: 59.1 ± 11.34 years; 34.6% hypertensive; 19.8% with diabetes) were analysed before and after receiving counselling from an oncology pharmacist. Pharmacist education significantly enhanced the mean patient necessity-concern balance scores by two-fold (MT0(baseline) = -3.1 ± 8.6; MT1(posteducation) =3.0 ± 7.3; p < 0.0001), with patients who received counselling for the first time experiencing the greatest benefit. Multivariate analysis showed that patients who had a negative balance between their beliefs about the necessity of the medication and their concerns were less likely to adhere to the medication (0.138 (0.025-0.772)). CONCLUSION: Counselling by an oncology pharmacist was effective in decreasing patient concerns and increasing their understanding of the necessity of the medication, thus enhancing their adherence and consequently improving the care they received.

The role of the pharmacist in the multidisciplinary approach to the prevention and resolution of drug-related problems in cancer chemotherapy.

BACKGROUND: Clinical pharmacists have important roles in implementing scientifically valid knowledge and advice on safe, reasonable use of pharmaceuticals. Clinical pharmacy services were introduced and evaluated in oncology clinic in a tertiary university hospital. METHODS: A prospective interventional study was conducted from November 2017 to March 2018. Drug-related problems were classified using the Pharmaceutical Care Network Europe drug-related problem classification tool v8.01. The main outcome measure is the proposed interventions aimed at identification of the drug-related problems, the role of the pharmacists in the resolution, and the rate of acceptance of these recommendations by physicians. RESULTS: A total of 102 patients were included in the study, who were treated with at least two cycles of any cancer type and stage. A total of 55 (53.9%) patients had 251 drug-related problems. Drug-related problems mainly involved antihypertensive (31.6%), antidiabetic (17.8%), and herbal agents (31.6%). Treatment effectiveness was the major type of drug-related problems (50.2%) followed by treatment safety (29.1%). A total of 211 (100%) interventions were accepted and regarded as clinically relevant. Prescriber informed only were the most common types of intervention at the prescriber level. Eighty-six point four percent identified drug-related problems were solved, 9.8% of the problems were partially solved, 2.3% problems were unsolved. CONCLUSION: Clinical pharmacy services may have optimized therapy effectiveness, prevent adverse effects and unclear/compliant problems. The pharmacist interventions were highly acknowledged by oncologists and patients; this may indicate the presence of a great convenience and need to implement Clinical pharmacy services in alternative hospitals in Northern Cyprus.

Optic atrophy after cabazitaxel treatment in a patient with castration-resistant prostate cancer: a case report.

Taxanes are a group of cytotoxic anti-cancer agents used in the treatment of solid tumours. The neurotoxic adverse effects of docetaxel and paclitaxel, including optic neuropathy, are well known. Cabazitaxel is a new generation taxane showing lesser drug resistance when compared with previous ones. Optic atrophy due to the use of cabazitaxel has not been previously reported. Herein, we report a patient with prostate cancer who developed optic atrophy after cabazitaxel treatment.

Correlation of educational status and clinicopathological characteristics of breast cancer: a single center experience.

PURPOSE: Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis. METHODS: The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. RESULTS: In all patient, a significant relationship was found between educational status and T stages (p<0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1). CONCLUSION: The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis.

Chemotherapy might not be beneficial in lymph node- negative, hormone-positive, and HER2-negative breast cancer patients: a long-term retrospective analysis.

INTRODUCTION: In lymph node-negative, hormone-positive, and Her2-negative breast cancer patients, the benefits of adding adjuvant chemotherapy to hormonal therapy continue to be debated, especially for low to intermediate grade and small tumors. METHODS: Excluding patients with T4 disease, we retrospectively reviewed the records of patients with long-term follow-up at our center between 2003 and 2014. Among node-negative, hormone-positive and HER2-negative breast cancer patients, we compared two groups of patients: those given both chemotherapy (doxorubicin+cyclophosphamide) and hormonotherapy, and those prescribed hormonotherapy alone. The primary endpoints were progression-free (PFS) and overall survival (OS). RESULTS: Overall, no difference was observed between these two treatment groups in either DFS or OS. However, for both outcomes, there was a trend towards improved DFS and OS favoring the hormone-only group. CONCLUSIONS: In selected subgroups of breast cancer patients, administering adjuvant hormonal therapy alone seems to be at least as good if not better than combining hormonotherapy and chemotherapy.

A retrospective analysis of adjuvant CAF, AC-T and TAC regimens in triple negative early stage breast cancer.

PURPOSE: To compare the effectiveness of adjuvant chemotherapy regimens in triple negative breast cancer (TNBC) for which no protocol has been determined to be treatment of choice. METHODS: In this single-center retrospective trial, we analyzed the adjuvant regimens of 164 TNBC patients among 3253 breast cancer patient records. Adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), CAF (cyclophosphamide, doxorubicin, 5fluorouracil), and AC-T (doxorubicin, cyclophosphamide followed by docetaxel) regimens were compared in terms of disease free survival (DFS) and overall survival (OS). RESULTS: In terms of both DFS and OS TAC was significantly superior to AC-T in node positive TNBC. When node negative and positive patients were analyzed together, TAC was still significantly superior to AC-T in terms of DFS and OS. There was a trend favoring CAF over AC-T, however, it was only significant in terms of OS when all node negative and positive TNBC patients were incorporated together. CONCLUSION: In the adjuvant setting, especially in node positive patients, TAC should be the treatment of choice in TNBC patients. CAF is probably better than AC-T in TNBC.