Real-world evaluation of nivolumab in patients with non-nasopharyngeal recurrent or metastatic head and neck cancer: a retrospective multi-center study by the Turkish Oncology Group (TOG).

OBJECTIVES: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. DESIGN: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. RESULTS: Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4-15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. CONCLUSIONS: Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes.

The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study.

INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group.

PURPOSE: Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC. METHODS: This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. RESULTS: A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7-7.8), and 11.9 months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable. CONCLUSION: This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC.

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.

Prognostic impact of immune inflammation biomarkers in predicting survival and radiosensitivity in patients with non-small-cell lung cancer treated with chemoradiotherapy.

INTRODUCTION: The purpose of this retrospective study was to investigate the prognostic impact of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived NLR (dNLR) and systemic immune-inflammation index (SII) in predicting outcomes for patients with locally advanced non-small-cell lung cancer (NSCLC). The secondary endpoint was to evaluate the radiosensitivity in terms of response rate. METHODS: Newly diagnosed locally advanced NSCLC patients were enrolled. Immune inflammation biomarkers were calculated from baseline blood samples. Patients were stratified in two groups based on optimal cut-off values for each biomarker. The associations between biomarkers and overall survival (OS), progression-free survival (PFS), local regional recurrence-free survival (LRRFS), and also response to radiotherapy were analysed. RESULTS: A total of 392 patients were included. Five-year OS, PFS and LRRFS rates were 14.6%, 12.1%, and 13.4% respectively. Optimal cut-off values for NLR, PLR, dNLR and SII were 3.07, 166, 2.02 and 817 respectively. Low NLR (HR 1.73, 95% CI 1.34-2.24, P < 0.001), low PLR (HR 1.37, 95% CI 1.06-1.76, P = 0.013), low dNLR (HR 1.66, 95% CI 1.29-2.13, P < 0.001) and low SII (HR 1.63, 95% CI 1.18-2.04, P < 0.001) were independent prognostic factors for OS. Low NLR, PLR, dNLR and SII were also significant prognostic factors for PFS and LRRFS. Low NLR, low dNLR and low SII groups had better radiosensitivity than compared with high NLR, high dNLR and high SII groups (P = 0.001, P = 0.001 and P = 0.012). CONCLUSION: NLR, PLR, dNLR and SII were independently associated with improved OS, PFS and LRRFS. Low NLR, dNLR and SII groups had better radiosensitivity. Immune inflammation biomarkers are promising prognostic predictors which can be obtained easily and inexpensively.

PD-L1 Expression in Medullary Thyroid Carcinoma and Its Association with Clinicopathological Findings.

< strong > Objective: < /strong > Medullary thyroid carcinoma (MTC) is a rare tumor originating from parafollicular C cells. It has more aggressive biologic behavior than differentiated thyroid carcinomas, and it is insensitive to treatment with radioactive iodine. Vandetanib and cabozantinib are the newly approved tyrosine kinase inhibitors in advanced stages, but novel effective systemic therapeutics could be crucial and needed for the clinical management of these patients. We aimed to evaluate the Programmed death-ligand 1 (PD-L1) expression, which is a novel immunotherapy target, in our MTC cohort, and determine whether it has an association with clinical and pathological features. < strong > Material and Method: < /strong > This retrospective study involved 41 cases of MTC with a median follow-up of 54 months. PD-L1 monoclonal antibody (SP263 clone) was investigated immunohistochemically. Complete and/or partial membranous staining pattern in more than 1% of tumor cells was considered positive. The correlations of PD-L1 expression with clinicopathologic and prognostic features were analyzed. < strong > Results: < /strong > PD-L1 positivity was detected in 5 (12.2%) of 41 tumors. The extent of PD-L1 staining was low ( < 5%) for all tumors. There was no clinicopathologic and prognostic relevance regarding PD-L1 expression in our MTC patients. < strong > Conclusion: < /strong > Although PD-L1 expression could be a potential biomarker to predict the prognosis of various cancers and response to checkpoint inhibitors, we did not find any significant correlation between PD-L1 expression and clinicopathologic features in our cases. Studies with larger patient numbers are still required to perform a more comprehensive analysis.

The Frequency of Human Papilloma Virus in Laryngeal Squamous Cell Carcinoma.

The association of HPV in laryngeal squamous cell carcinoma (LSCC) is investigated in several studies but controversial results are established. This study aimed to investigate the HPV DNA positivity in LSCC patients diagnosed and treated in two otorhinolaryngology referral centres in northern region of Turkey. The study was planned as a retrospective investigation of LSCC patients. Fifty-two formalin-fixed, paraffin-embedded (FFPE) tissue blocks of laryngeal cancers-diagnosed and treated between 2010 and 2016, were included. Polymerase chain reaction (PCR) method was used for detection of HPV genotypes. PCR amplification was successful in 40 of 52 patients. Among the 40 LSCC samples, HPV DNA was detected in one patient (2.5%). The evaluated HPV positivity in LSCC as low; but larger studies are needed to confirm this.

Cutaneous metastasis of colon adenocarcinoma.

Skin metastasis originating from colorectal cancer is a rare entity and usually signifies poor prognosis. We present a case of a 62-year-old male patient who presented with a cutaneous metastatic focus on his forehead after five years of the primary treatment of colon cancer. Complete response from the cutaneous metastasis nodule was achieved with radiotherapy. The patient is still alive and under a second-line palliative chemotherapy regimen because of the multiple liver metastases. It is important for physicians to be aware of skin metastasis in patients with an oncology history.

Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour in adults. Identification of accessible and cost-effective prognostic factors may better guide adjuvant treatment-related decisions. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of host inflammatory response, and their increase has recently been shown to be a poor prognostic factor in several malignancies. The aim of the present study was to investigate the prognostic value of preoperative NLR and PLR in GBM patients. Between 2012 and 2017, 104 patients who had undergone surgery for GBM were considered for adjuvant therapy in our institution. Of those, 80 patients with evaluable pre-corticosteroid full blood count results were identified and included in the final analysis. The Eastern Cooperative Oncology Group performance status, localization, radiochemotherapy and second-line systemic therapy were found to be independent prognostic indicators for progression-free and overall survival. The median overall survival was 13.2 months. Patients with NLR <4 had a better median overall survival of 10.7 vs. 7.8 months in patients with NLR >4; however, this difference was not statistically significant (P>0.05). Overall survival also did not differ significantly between patients with low and those with high PLR values (10.2 vs. 15.2 months, respectively; P=0.105). In conclusion, the results of the present study suggest that pre-treatment NLR and PLR do not have prognostic value in GBM patients; however, large-scale trials are required to confirm these findings.

Epithelial membrane protein 1 expression in ovarian serous tumors.

The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were retrospectively analyzed. Differences in the expression levels of EMP1 between the malignant and non-malignant tumor groups were evaluated by immunohistochemical staining. In addition, the association between EMP1 expression and prognostic factors in malignant ovarian serous tumors was investigated. The expression levels of EMP1 were significantly reduced in all the 50 malignant ovarian serous tumors, compared with the 34 non-malignant ovarian serous tumors (P<0.000). Reduced expression of EMP1 was correlated with high grade (P=0.009) and stage (P<0.000) of malignant tumors. EMP1 expression was not observed to be correlated with any other investigated parameters, including surgery, type of operation and chemotherapy response (P>0.005). These results indicated that EMP1 may have a significant role as a negative regulator in ovarian serous tumors, and reduced EMP1 expression in serous tumors may be associated with increased disease severity.

Antithyroid peroxidase antibody positivity is associated with lower incidence of metastasis in breast cancer.

Thyroid extracts were first used to treat patients with metastatic breast cancer over a century ago. Since then, a number of studies have investigated the association between thyroid disorders and breast cancer. The presence of antibodies to thyroid peroxidase (TPOab) was recently reported to be associated with improved outcome in these patients. The aim of the present study was to evaluate the association between TPOab positivity and clinicopathological characteristics in breast cancer patients. The study included 318 newly diagnosed cases of breast cancer treated at Ondokuz Mayis University Hospital, Samsun, Turkey, between 2008 and 2012. Serum thyroid-stimulating hormone, free triiodothyronine and free thyroxine levels were measured at the time of diagnosis. Of the 318 patients, 253 were considered to be TPOab-negative (TPOab ≤34 IU/ml) and 65 TPOab-positive (TPOab >34 IU/ml). No cases with distant metastases were found in the TPOab-positive group. However, 20 (7.9%) of the 253 patients displayed distant metastases in the TPOab-negative group (P=0.01). Therefore, TPOab positivity was found to be associated with a lower incidence of metastasis in breast cancer patients.

Quality of life in colorectal cancer patients during chemotherapy in the era of monoclonal antibody therapies.

PURPOSE: Colorectal cancer (CRC) survivors are currently living longer due to better therapies but they also need to maintain their quality of life (QoL). QoL is increasingly being used as primary outcome measure in clinical studies. This study was designed to gain knowledge about QoL during chemotherapy across different lines and different regimens. METHODS: The study comprised 101 CRC out patients receiving chemotherapy who completed the EORTC QLQ-C30 questionnaire. The Shapiro-Wilk, Kruskal-Wallis, and Mann-Whitney U tests were used for statistical analyses. RESULTS: The demographics of the patients were evaluated for QoL. Prior surgery, prior radiotherapy, working status, stage, comorbidity and sex had no effect on global health status in CRC patients, although some other demographics such as education, monthly income, age and type of chemotherapy regimen did have an effect on global health status. Role functioning was worse in older than in younger ones (p<0.05). Adjuvant chemotherapy did not affect the QoL scores negatively but palliative chemotherapy negatively affected the cognitive function, appetite loss and nausea/vomiting scores (p<0.05). According to chemotherapy regimen, the best QoL was observed with adjuvant FUFA regimen. In the palliative setting FOLFOX/Bevacizumab was associated with the best QoL scores whereas FOLFIRI/Cetuximab were associated with the worst QoL scores. CONCLUSIONS: Palliative chemotherapy maintained QoL irrespective of the chemotherapy line in metastatic CRC (mCRC) patients. Some demographics affect QoL and different chemotherapy regimens showed different QoL scores.

The value of red blood cell distribution width in endometrial cancer.

BACKGROUND: Red cell distribution width (RDW) is a routinely examined parameter with the complete blood count. In recent studies, RDW levels have been associated with cardiovascular, liver and renal diseases and solid tumors. The aim of this study was to evaluate the alterations of RDW levels in benign and malignant causes of postmenopausal bleeding and to investigate the association of RDW levels with clinicopathological parameters of endometrial cancer (EC) patients. METHODS: A retrospective study was made of a total of 884 females who were admitted to hospital for postmenopausal bleeding between May 2009 and December 2013. After inclusion and exclusion criteria were applied, 222 patients remained. Complete blood count data was obtained from the recorded computerized database. After pathological evaluation, the patients were divided into two groups, benign and malignant (EC). RESULTS: The EC group (n=113) had significantly higher RDW levels compared to the benign group (14.78±2.02 vs. 13.88±1.05; p=0.000). Grade II and above EC patients had higher levels of RDW than Grade I patients (15.2±2.3 vs. 14.1±1.00; p=0.005). Correlation analyses also revealed a negative correlation between RDW and hemoglobin levels (p=0.000), RDW and mean corpuscular volume (p=0.000), RDW and lymphocyte count (p=0.035) but a positive correlation between RDW and platelet to lymphocyte ratio (p=0.030). CONCLUSIONS: The results of the current study revealed the potential predicitve role of RDW in patients with postmenopausal bleeding. Significant associations were also determined between RDW and clinicopathological characteristics in EC patients.

A case of gastric cancer with liver metastases had a complete response with cisplatin and capecitabine as third-line chemotherapy.

Advanced gastric cancer has a poor prognosis, and only chemotherapy improves survival. Further chemotherapy after progression is controversial. Eastern Cooperative Oncology Group performance status is an important indicator for new chemotherapy decision. Complete response (CR) after recurrent disease is very rare, but could occur in some cases with chemotherapy. The 68-year-old male received chemotherapy for metastatic gastric adenocarcinoma. He received epirubicin, cisplatin and fluorouracil in the first line, capecitabine in the second line and cisplatin-capecitabine in the third line. CR was observed after third-line chemotherapy with four courses. Mediastinal and abdominal metastases were completely resolved. We decided to report this patient because it is very unusual to achieve CR in a patient in whom the best supportive care might be reasonable.

Efficacy and safety of docetaxel or epirubicin, combined with cisplatin and fluorouracil (DCF and ECF), regimens as first line chemotherapy for advanced gastric cancer: a retrospective analysis from Turkey.

OBJECTIVES: Advanced gastric cancer (AGC) patients have a poor prognosis. The best benefit of chemotherapy is usually achieved by first line setting. Very few studies have compared combination regimens. This study was designed to compare two combination regimens. METHODS: Patients with advanced gastric cancer receiving first line chemotherapy were retrospectively collected, and divided into two groups, receiving DCF (docetaxel, cisplatin and fluorouracil) or ECF (epirubicin, cisplatin and fluorouracil) regimens. Data were collected for the retrospective analysis in a single center. RESULTS: Eighty-six patients were eligible for analysis. Median overall survival (OS) was 10.0 months in the ECF group and 11.0 months in the DCF group (p=0.31). Median progression free survival (PFS) for ECF and DCF was equal at 6.0 months. Second line chemotherapy were administered in more than one third of patients. Both regimens had similar toxicity. CONCLUSIONS: This is the first study investigating the outcomes of gastric cancer chemotherapy in this region. ECF and DCF regimens have similar efficacy and a similar tolerability profile for first line treatment of advanced gastric cancer. The decision of the first line chemotherapy in advanced gastric cancer could be improved with patient selection according to clinical parameters and molecular markers.

Elevated serum neutrophil to lymphocyte and platelet to lymphocyte ratios could be useful in lung cancer diagnosis.

BACKGROUND: Lung cancer (LC) is still the primary cause of cancer deaths worldwide, and late diagnosis is a major obstacle to improving lung cancer outcomes. Recently, elevated preoperative or pretreatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) detected in peripheral blood were identified as independent prognostic factors associated with poor survival with various cancers, including colon cancer, esophageal cancer, gastric cancer and breast cancer. OBJECTIVE: The aim of this study was to examine whether MPV, NLR and PLR could be useful inflammatory markers to differentiate lung cancer patients from healthy controls. An investigation was also made of the relationship between these markers and other prognostic factors and histopathological subgroups. MATERIALS AND METHODS: Retrospectively eighty-one lung cancer patients and 81 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. The preoperative or pretreatment blood count data was obtained from the recorded computerized database. RESULTS: NLR and PLR values were significantly higher in the LC patients compared to the healthy subjects.( NLR: 4.42 vs 2.45 p=0.001, PLR: 245.1 vs 148.2 p=0.002) MPV values were similar in both groups (7.7 vs 7.8). No statistically significant relationship was determined between these markers (MPV, NLR and PLR) and histopathological subgroups and TNM stages. CONCLUSIONS: NLR and PLR can be useful biomarkers in LC patients before treatment. Larger prospective studies are required to confirm these findings.

Clinicopathological characteristics of thyroid cancer in patients on dialysis for end-stage renal disease.

BACKGROUND: The prevalence rate of thyroid cancers in patients with renal failure is variable in different studies. Our aim was to determine the prevalence and clinicopathological characteristics of thyroid cancers in the dialysis population and to evaluate the potential risk factors. METHODS: We performed a retrospective analysis on end-stage renal disease (ESRD) patients on dialysis and thyroidectomized patients without ESRD (2000-2006). Then we compared the data of thyroid cancer patients on dialysis (n = 9) with the data of patients who had histopathologically verified benign thyroid disease on dialysis (n = 23) and with the histopathological data of thyroid cancer patients without ESRD. RESULTS: Papillary thyroid cancer (PTC) was the only histotype that was found in 9 of 420 (2.1%) ESRD patients on dialysis. Multifocal PTC was found in eight of nine patients; of them, four had follicular variant of PTC (FVPTC). Two patients had lymphatic metastasis at diagnosis. Eight PTCs were classified as tumor-node-metastasis (TNM) stage I and one as stage II. Among the analyzed factors, age (r = 0.374, p = 0.01) and duration of dialysis (r = 0.436, p = 0.007) showed a significant positive correlation with the occurrence of thyroid cancer. CONCLUSIONS: We conclude that the prevalence of thyroid cancer in patients undergoing dialysis was not higher than that in the background population. Age and duration of dialysis showed a significant positive correlation with the occurrence of thyroid cancer in patients on dialysis. Among the histotypes, there may be higher percentage of PTC, FVPTC, and multifocality in dialysis patients. The effect of these characteristics on prognosis of thyroid cancer in dialysis patients is needed to be further evaluated.