Sonographic Measurements of Rectus Femoris Muscle Thickness Strongly Predict Neutropenia in Cancer Patients Receiving Chemotherapy.

The objective of this study was to explore the possible association between low skeletal muscle mass (SMM)-assessed by computed tomography (CT) and ultrasound (US)-and hematologic toxicity in cancer patients. A prospective cohort study was conducted in cancer patients who received anthracycline-based chemotherapy between 2018 and 2020 and who had baseline abdominal CT including L3 level for measuring SMM. Regional muscle measurements were carried out using US. A total of 65 patients (14 males, 51 females) were included. ROC (receiver operating characteristic) analysis identified threshold values of 18.0 mm [AUC (area under the curve) = 0.765] for females and 20.0 mm (AUC = 0.813) for males, predicting severe neutropenia. Using these cut-offs, females with low rectus femoris (RF) thickness (<18.0 mm) had a significantly higher incidence of grade ≥3 neutropenia (50.0% vs. 10.8%, p = 0.005), and males with low RF values (<20.0 mm) had a higher incidence (80.0% vs. 22.2%, p = 0.063). A regression analysis, irrespective of age, gender, and body mass index, revealed that only low RF muscle thickness increased the risk of grade 3-4 neutropenia by 9.210 times (95% CI = 2.401-35.326, p = 0.001). Utilizing US to measure RF muscle thickness aids in identifying cancer patients at an elevated risk of developing neutropenia. Needless to say, US can serve as a convenient and easily accessible tool for assessing low SMM, providing repeat point-of-care evaluations in clinical practice.

The Prognostic Significance of KIAA1522 Expression in Non-Small-Cell Lung Cancer Patients.

The majority of lung cancers belong to the non-small-cell lung cancer (NSCLC) category, which is linked to a high mortality rate despite significant progress in diagnosis and treatment. Therefore, there is a need for novel prognostic NSCLC biomarkers to improve prognosis which currently remains poor. Recent studies and analyses of gene expression data of NSCLC revealed that high expression of KIAA1522 was significantly associated with poor prognosis and decreased overall survival. We identified 98 patients who underwent radical curative surgical resections or metastasectomy for pulmonary adenocarcinoma and squamous cell carcinoma at our institution or the pathological diagnosis confirmed by our pathologists. Following the latest data, we utilized immunohistochemistry to assess the expression of KIAA1522 and investigated its association with various clinic-demographic parameters, pathological stages, recurrence rates, overall survival, and disease-free survival in patients who achieved complete remission. Notably, there were no significant differences in the expression profiles of KIAA1522 between adenocarcinoma and squamous cell carcinoma samples (p=0.6). Survival analysis was conducted using log-rank tests and a multivariate Cox proportional hazard model. Of the 98 samples, 54 (55.1%) exhibited high expression of KIAA1522, and patients with high KIAA1522 expression had a significantly shorter overall survival than the low-expression group (p=0.01). Multivariate Cox proportional hazard models in which metastatic patients were included revealed that along with older age, higher TNM stage (tumor, node, metastasis system), and Eastern Cooperative Oncology Group (ECOG) performance status, high expression of KIAA1522 served as an independent prognostic factor. A high expression profile was not significantly associated with relapses in those whose complete remission had been achieved. Still, those patients with high expression of KIAA1522 tended to exhibit a shorter disease-free survival rate. In conclusion, our findings suggest that KIAA1522 expression is an independent factor for predicting overall survival and may serve as a valuable prognostic indicator for relapse and disease-free survival in NSCLC patients.

Prognostic and predictive value of tumor infiltrating lymphocytes in combination with systemic inflammatory markers in colon cancer.

OBJECTIVE: Systemic inflammatory indices and CD8(+) tumor infiltrating lymphocytes (TILs) in the tumor microenvironment are highly prognostic in colon cancer (CC) but combined assessment is less well studied. The purpose of this study was to investigate the prognostic and predictive value of CD8(+) TILs in combination with systemic inflammatory indices in patients with resected stage II-III colon cancer. PATIENTS AND METHODS: Patients with stage II-III CC (n = 304) diagnosed between 2008 and 2016 were included. Pan-immune inflammation value (PIV) was used as a comprehensive inflammatory index and was calculated as: [neutrophil count × platelet count × monocyte count]/lymphocyte count. The mean density of CD8+ TILs in the periphery and center of the tumor was assessed and dichotomized at the 75th percentile. Combined inflammation score (CIS) was classified as "high" in patients with high PIV (>median) plus low mean CD8(+) TILs density, and CIS "low" in the remaining patients. RESULTS: 5-year DFS was 71% (78% in stage II, 63.4% in stage III). PIV was higher in right colon tumors, T4 tumors and in patients with obstruction / perforation. CD8(+) TIL density was lower in node positive tumors. High PIV and low CD8(+) TILs were associated with shorter disease-free survival (DFS). In multivariate analysis; age > 65 years, stage III disease and high CIS (PIVhigh / CD8low) were associated with shorter DFS. Among patients with stage II disease, patients with high CIS (PIVhigh / CD8low) derived significant benefit from adjuvant chemotherapy while those with low CIS derived no benefit. CONCLUSION: Combined inflammation score may represent a new prognostic factor for localized colon cancer and predictor of chemotherapy response in patients with stage II disease.

Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer.

OBJECTIVE: DNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC. PATIENTS AND METHODS: Patients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed. RESULTS: 130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48-9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04-3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13-5.48, p = 0.023) and high post-operative CA 19-9 level (>100 IU/ml) (HR:2.61 95% CI 1.40-4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53. CONCLUSION: Contrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.

Blood Based Biomarkers as Predictive Factors for Hyperprogressive Disease.

Purpose: With the widespread use of immunotherapy agents, we encounter treatment responses such as hyperprogression disease (HPD) that we have not seen with previous standard chemotherapy and targeted therapies. It is known that survival in patients with HPD is shorter than in patients without HPD. Therefore, it is important to know the factors that will predict HPD. We aimed to identify HPD-related factors in patients treated with immunotherapy. Methods: A total of 121 adult metastatic cancer patients treated with immunotherapy for any cancer were included. Baseline demographics, the ECOG performance status, type of tumors and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. Results: The median age was 62.28 (interquartile range (IQR) 54.02−67.63) years, and the median follow-up was 12.26 (IQR 5.6−24.36) months. Renal cell carcinoma (33%) and melanoma (33.8%) were the most common diagnoses. Twenty patients (16.5%) had HPD. A high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007) were found to be associated with hyperprogression. Sex (female vs. male, p: 0.114), age (>65 vs. <65, p: 0.772), ECOG (0 vs. 1−4, p: 0.480) and the line of treatment (1−5, p: 0.112) were not found to be associated with hyperprogression. Conclusions: In this study, we observed HPD in 16.5% of immunotherapy-treated patients and increased HPD risk in patients with a high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007).

Crizotinib Efficacy After Progression With Entrectinib in ROS1-Positive Lung Cancer: A Case Report.

Crizotinib and entrectinib are approved tyrosine kinase inhibitors by the FDA to treat advanced-stage ROS1-positive non-small cell lung cancer (NSCLC). Although, entrectinib could be used after crizotinib, it is unknown whether crizotinib is effective after entrectinib. We report a case of NSCLC with ROS1 rearrangement that achieved a nearly complete response with crizotinib in the second-line treatment after progression with entrectinib. A 22-year-old Caucasian non-smoker female patient was diagnosed with stage IV non-squamous lung cancer with ROS1 positivity. We started on entrectinib as first-line therapy. Due to progression in the 10th month of treatment, entrectinib was stopped and crizotinib was started as a second-line treatment. At the end of the third month of the treatment, a nearly complete response was obtained in the follow-up imaging. The patient is still being followed up with crizotinib and is in the 15th month of treatment. Based on our experience, crizotinib can be an option as second-line therapy in patients who are treated with entrectinib in the first line, especially in patients without brain metastasis.

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.

Prognosis of Liposarcoma Patients in Modern ERA: Single-Center Experience.

Objective Liposarcomas are relatively rare tumors. Prognostic and predictive factors and treatment options are limited. We herein presented our 10-year experience with liposarcomas. Materials and Methods Adult patients with liposarcoma treated between 2005 and 2015 in our center were included. Demographic and clinicopathologic features of patients were retrieved from patient files. Statistical Analyses Outcomes in terms of disease-free survival (DFS) and overall survival (OS) were assessed along with potential prognostic factors using Kaplan-Meier analyses. Results A total of 88 patients were included. The median age was 52. Rates of well-differentiated (WDLS), dedifferentiated (DDLS), myxoid (MLS), and pleomorphic liposarcomas (PLS) were 42, 9.1, 37.5, and 4.5%, respectively. Only 10% of patients had high-grade tumors and 93% had localized disease. Ninety-six percent of patients ( n = 84) underwent surgery. Adjuvant chemotherapy was delivered to 16 patients. The most common regimen was ifosfamide-doxorubicin. Recurrences were observed in 30 patients, 21 had local, and 9 had distant metastasis. Five-year DFS of patients with the localized disease was 68%. All patients with PLS had relapses and those had the highest distant relapse rates among all subtypes. Multivariate analysis showed T stage and grade were associated with DFS. Five-year OS of the entire population was 68%. Five-year OS was 79, 76, 50, and 0% in WDLS, MLS, DDLS, and PLS, respectively ( p = 0.002). Conclusion Management of liposarcomas is still challenging. Surgery is the mainstay of treatment. Novel effective therapies are needed, particularly in advanced disease settings.

Nivolumab in metastatic renal cell carcinoma: results from the Turkish Oncology Group Kidney Cancer Consortium database.

Aim: The authors present real-world data on the efficacy and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) database includes patients with mRCC from 13 cancer centers in Turkey. Patients with mRCC treated with nivolumab in the second line and beyond were extracted from the TKCC database. Results: A total of 173 patients were included. The rates of patients treated with nivolumab in the second, third, fourth and fifth lines were 47.4%, 32.4%, 14.5% and 5.7%, respectively. The median overall survival and progression-free survival were 24.2 months and 9.6 months, respectively. Nivolumab was discontinued owing to adverse events in 11 (6.4%) patients. Conclusion: Nivolumab was effective in patients with mRCC and no new safety signal was observed.

Lay abstract Nivolumab is an immune checkpoint inhibitor (ICI) that blocks the communication between T cells and cancer cells and instead activates T cells to fight against cancer. Metastatic renal cell carcinoma (mRCC) is one of the most susceptible tumors to ICIs. The Checkmate 025 trial showed the efficacy of nivolumab in patients with previously treated mRCC. In this real-world study, 173 patients with mRCC were treated with nivolumab in the second line and beyond. Nivolumab was effective in the real-world setting without additional safety concerns.

Lower prognostic nutritional index is associated with poorer survival in patients receiving immune checkpoint inhibitors.

Aim: Blood-based biomarkers like prognostic nutritional index (PNI) are readily available biomarkers for immunotherapy efficacy, although the data are limited. So, we aimed to evaluate the association between PNI and overall survival (OS) in immunotherapy-treated patients. Materials & methods: For this retrospective cohort study, data of 150 immunotherapy-treated advanced cancer patients were evaluated. The association between clinical factors and OS was evaluated with multivariate Cox-regression analyses. Results: After a median follow-up of 8.5 months, 94 patients died. The median OS was 11.07 months. The low PNI (hazard ratio [HR]: 2.065; p = 0.001), high lactate dehydrogenase (HR: 2.515; p = 0.001) and poor Eastern Cooperative Oncology Group (ECOG) status (HR: 2.164; p = 0.009) was associated with poorer OS in multivariate analyses. Conclusion: In our experience, survival with immunotherapy was impaired in patients with lower PNI and higher lactate dehydrogenase levels and poorer ECOG status.

Impact of albumin to globulin ratio on survival outcomes of patients with metastatic renal cell carcinoma.

OBJECTIVE: The albumin to globulin ratio (AGR) has been demonstrated to be associated with survival outcomes in various tumor types. However, the prognostic value of AGR in patients with metastatic renal carcinoma (mRCC) remains unclear. Therefore, this study aimed to investigate the impact of AGR values in predicting overall survival (OS) of patients with mRCC treated with targeted therapy. MATERIAL AND METHODS: A total of 163 patients with mRCC treated with targeted therapy between 2008 and 2019 were enrolled. The AGR value was measured as AGR: albumin/(total protein-albumin). The Kaplan-Meier method with long-rank testing and Cox proportional hazard models were used to estimate the correlation of AGR with OS. RESULTS: The receiver operating characteristic curve analysis showed that the optimal cut-off value of AGR in predicting OS was 1.11 with a sensitivity of 37.25% and specificity of 85.25% (area under curve, 0.62; 95% confidence interval [CI], 0.54-0.69; p=0.005). OS was significantly higher in patients with AGR>1.11 than in those with AGR≤1.11 (36.2 vs. 12.4 months; p<0.001). After adjustment for the number of covariates, multivariate Cox regression analysis identified a high AGR as an independent indicator of better OS (hazard ratio, 0.476; 95% CI, 0.304-0.745; p=0.001). CONCLUSION: Our results suggested that AGR value, which is an easily obtainable and cost-effective marker in routine biochemistry testing, could function as an independent predictor of OS in patients with mRCC treated with targeted therapy.

Poorer baseline performance status is associated with increased thromboembolism risk in metastatic cancer patients treated with immunotherapy.

PURPOSE: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. However, the association of VTE with immunotherapy remains poorly defined. We therefore evaluated the frequency of VTE in patients receiving immunotherapy and tried to determine predisposing factors. METHODS: A total of 133 adult metastatic cancer patients treated with immunotherapy for any cancer between were included. Baseline demographics, ECOG performance status, type of tumors, and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. RESULTS: The median age was 60 (interquartile range (IQR) 48-66) years, and the median follow-up was 10.1 (IQR 5.8-18.5) months. Renal cell carcinoma (26.3%) and melanoma (24.1%) were most common diagnoses. Fifteen patients (11.3%) had an episode of VTE. Most of the VTEs were diagnosed as pulmonary emboli (10/15; 67%). Eighty percent (12/15) of these VTE cases were detected incidentally. Patients with a baseline ECOG performance status of 1 or more (29.3% of patients) had a significantly increased risk of venous thrombosis (ECOG ≥1 vs. 0, HR: 3.023, 95% CI: 1.011-9.039, p=0.048). Other factors, including patient age, tumor type, body mass index, baseline thrombocyte, neutrophil, and lactate dehydrogenase levels were not significantly associated with VTE risk. CONCLUSIONS: In this study, we observed VTE development in more than 10% of immunotherapy-treated patients and increased VTE risk in patients with poorer ECOG status. With the asymptomatic nature of VTEs in most cases, a high index of suspicion level for VTE is required in patients treated with immunotherapy.

Evaluation of emergency departments visits in patients treated with immune checkpoint inhibitors.

BACKGROUND: The emergency department (ED) is a crucial encounter point in cancer care. Yet, data on the causes of ED visits are limited in patients treated with immune checkpoint inhibitors (ICI). Therefore, we evaluated ED visits in patients treated with ICIs in attempt to determine the predisposing factors. METHODS: We performed a retrospective chart review on adult cancer patients treated with ICIs for any type of cancer in the Hacettepe University Cancer Center. The data on ED visits after the first dose of ICIs to 6 months after the last cycle of ICIs were collected. RESULTS: A total of 221 patients were included in the study. The mean age was 58.46 ± 13.87 years, and 65.6% of patients were males. Melanoma was the most common diagnosis (27.6%), followed by kidney and lung cancers. Eighty-three of these patients (37.6%) had at least one emergency department (ED) visit. Most of the ED visits were related to symptoms attributable to the disease burden itself, while immune-related adverse events comprised less than 10% of these visits. While baseline Eastern Cooperative Oncology Group performance status, age, polypharmacy, concomitant chemotherapy, eosinophilia, and lactate dehydrogenase levels did not significantly increase the risk, patients with regular opioid use and baseline neutrophilia (> 8000/mm3) had a statistically significant increased risk of visiting the ED (p = 0.001 and 0.19, respectively). These two factors remained significant in the multivariate analyses. CONCLUSION: In this study, almost 40% of ICI-treated patients had ED visits. Collaboration with other specialties like emergency medicine is vital for improving the care of patients receiving immunotherapy.

Neutrophil-lymphocyte ratio as a prognostic factor for survival in patients with advanced renal cell carcinoma (Turkish Oncology Group Study).

BACKGROUND: To describe the prognostic value of neutrophil-lymphocyte ratio and its effect on survival in in patients with advanced renal cell carcinoma. METHODS: We retrospectively analyzed 331 patients. The cut-off value of neutrophil-lymphocyte ratio was specified as "3" which is mostly close-and also clinically easily applicable-to the median neutrophil-lymphocyte ratio level of our study group. High group is identified as neutrophil-lymphocyte ratio >3 (n = 160) and low group is identified as neutrophil-lymphocyte ratio ≤3 (n = 163). RESULTS: A total of 331 (with 211 male and 120 female) patients were enrolled to study. The median age of the patients was 58. The International Metastatic RCC Database Consortium risk score is calculated for the 72.8% (n = 241) of the study group and among these patients, favorable, intermediate, and poor risk rates were 22, 45.2, and 32.8%. The total usage of tyrosine kinase inhibitors reached 78% of the patients. The median overall survival was 32 months versus 11 months in the neutrophil-lymphocyte ratio low and high groups, respectively (HR: 0.49 (95% CI 0.37-0.65), p < 0.001). CONCLUSION: In conclusion, the pre-treatment value of elevated neutrophil-lymphocyte ratio might be a predictor of poor overall survival in advanced renal cell carcinoma patients.

Development of de novo psoriasis during nivolumab therapy in a patient with small cell lung cancer.

INTRODUCTION: The immune checkpoint inhibitors recently entered to small cell lung cancer (SCLC) stage, firstly in the third and recently in the first lines of therapy. This efficacy comes at the expense of many toxicities including skin toxicity. This toxicity is usually in the form of rash and pruritis; however, rare reactions like psoriasis can also be seen. CASE REPORT: Herein, we report an SCLC case who developed de novo psoriasis while treated with nivolumab as the third-line treatment for SCLC. MANAGEMENT AND OUTCOME: The psoriatic plaques were regressed with the topical highly potent steroid therapy, and immunotherapy was continued without further complications. DISCUSSION: We think that rare adverse events like de novo psoriasis are important considering the expanding role of these agents; their timely recognition and treatment are important in the management of cancer patients.

The relationship between prognostic nutritional index and treatment response in patients with metastatic renal cell cancer.

INTRODUCTION AND AIM: To investigate the effect of the prognostic nutritional index on treatment response and survival in patients with metastatic renal cell cancer. METHODS: We retrospectively analyzed the treatment modalities; the demographic, clinical and pathological features of 396 patients with RCC and prognostic nutritional index. Based on the median value, patients were grouped as having low and high prognostic nutritional index values. Kaplan-Meier method was used for survival analysis, and Cox-regression analysis was used for multivariate analysis. RESULTS: The median overall survival was 39 months (95% CI 26.1-51.8), 28 months (95% CI 17.9-38) and 7 months (95% CI 4.7-9.2) in patients with favorable, intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium risk group, respectively. The difference between the groups was statistically significant (p < 0001). Overall survival was 11 months (95% CI 7.5-14.5) in the low-prognostic nutritional index (prognostic nutritional index ≤38.5) group, and 41 months (95% CI 30.5-51.4) in the high prognostic nutritional index (prognostic nutritional index >38.5) group (p < 0.001). In Cox regression analysis, Eastern Cooperative Oncology Group performance score (HR: 2.5), time to systemic treatment (HR: 1.7) and prognostic nutritional index (HR: 1.8) were associated with overall survival. CONCLUSION: In patients with renal cell cancer, prognostic nutritional index is closely related to survival and has prognostic significance.