Inflammatory parameters in NSCLC with driver mutation.

Aim: The tumor microenvironment of NSCLC with driver mutations, such as EGFR, ALK and ROS, is less inflammatory. Materials & methods: This retrospective study included 38 patients with NSCLC driver mutations. The relationship between clinical and inflammatory markers concerning progression-free survival and overall survival was analyzed based on Kaplan-Meier curves. Results: The mean age of the patients was 59.8 ± 11.9. Progression-free survival and overall survival were significantly longer in patients under 65 years of age and with low neutrophil-lymphocyte ratio, low systemic immune-inflammation index and high lymphocyte count (p < 0.05). Conclusion: Unlike tumor biology, peripheral inflammatory parameters, such as neutrophil-lymphocyte ratio, systemic immune-inflammation index and lymphocyte count may be associated with survival in NSCLC patients with driver mutations.

Lung cancer is the most common cancer worldwide and has a high mortality rate. Overall survival expectancy in metastatic NSCLC has increased from 11 months to 18 months. The detection of targeting mutations and the introduction of targeted treatments are the factors that increase overall survival. The contribution of immunotherapy to NSCLC is indisputable. The contribution of immunotherapy is low in NSCLC with driver mutation. We found that survival was associated with peripheral parameter indicators of inflammation despite the less inflamed tumor microenvironment. For immunotherapy to be effective in NSCLC, where there are not many treatment options, investigating different immune checkpoints or escape mechanisms and treatment planning for these will further improve survival.

Peripheral inflammatory parameters may be associated with survival in driver mutation NSCLC, in contrast to a less inflammatory tumor microenvironment.

A novel prognostic biomarker in progression free survival for patients with cervical cancer, glucose to c-reactive protein ratio (GCR).

BACKGROUND: Cervical cancer is a tumor with high morbidity and mortality. The importance of inflammatory and metabolic parameters affecting progression-free survival (PFS) and overall survival (OS) has been investigated more intensively recently. We aimed to investigate the effect of glucose/c-reactive protein (CRP) ratio [GCR], which shows these two parameters together, on PFS in cervical cancer. METHODS: We retrospectively included 90 patients with adenocarcinoma and squamous cell carcinoma of the cervix. The effects of clinical variables, inflammatory and glycemic parameters on PFS and OS were analyzed by Kaplan-Meier method. The data were compared with the healthy control group of 90 individuals using the independent t test. The effect of parameters on mortality was analyzed using ROC curves and cut off values were determined. RESULTS: Glucose, CRP, CRP/lymphocyte ratio (CLR) and GCR were statistically significant in predicting mortality (p < 0.05). Disease stage, glucose, CRP, CLR and GCR were associated with overall survival. CRP, CLR and GCR were associated with progression-free survival (p < 0.05). In multivariate analysis, GCR was prognostic for PFS (p = 0.025). GCR was statistically significant while compared with the patient and healthy control group (p < 0.001). CONCLUSION: In cervical cancer, GCR rate was found to be prognostic independent of stage. Higher GCR rate was associated with longer PFS duration.

Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial.

BACKGROUND: Evidence for the efficacy of combined PD-1 and HER2 blockade with chemotherapy on progression-free and overall survival in HER2-positive gastro-oesophageal cancer is scarce. The first interim analysis of the randomised, phase 3 KEYNOTE-811 study showed a superior objective response with pembrolizumab compared with placebo when added to trastuzumab plus fluoropyrimidine and platinum-based chemotherapy. Here, we report results from protocol-specified subsequent interim analyses of KEYNOTE-811. METHODS: The randomised, phase 3 KEYNOTE-811 trial involved 168 medical centres in 20 countries worldwide. Patients aged 18 years or older with locally advanced or metastatic HER2-positive gastro-oesophageal junction adenocarcinoma, without previous first-line treatment, were randomly assigned (1:1) by an integrated interactive voice-response and web-response system to intravenous pembrolizumab 200 mg or placebo, both to be combined with standard chemotherapy (fluoropyrimidine and platinum-based therapy) plus trastuzumab every 3 weeks for up to 35 cycles or until disease progression, unacceptable toxic effects, or investigator or participant-initiated withdrawal. Randomisation used a block size of four and was stratified by region, PD-L1 status, and chemotherapy. Dual primary endpoints were progression-free and overall survival, analysed by intention to treat. Safety was assessed in all randomly assigned patients who received at least one dose of study treatment according to the treatment received. KEYNOTE-811 is registered with ClinicalTrials.gov (NCT03615326) and is active but not recruiting. FINDINGS: Between Oct 5, 2018, and Aug 6, 2021, 698 patients were assigned to pembrolizumab (n=350) or placebo (n=348). 564 (81%) were male and 134 (19%) were female. At the third interim analysis, 286 (82%) of 350 patients in the pembrolizumab group and 304 (88%) of 346 in the placebo group who received treatment had discontinued treatment, mostly due to disease progression. At the second interim analysis (median follow-up 28·3 months [IQR 19·4-34·3] in the pembrolizumab group and 28·5 months [20·1-34·3] in the placebo group), median progression-free survival was 10·0 months (95% CI 8·6-11·7) in the pembrolizumab group versus 8·1 months (7·0-8·5) in the placebo group (hazard ratio [HR] 0·72, 95% CI 0·60-0·87; p=0·0002). Median overall survival was 20·0 months (17·8-23·2) versus 16·9 months (15·0-19·8; HR 0·87 [0·72-1·06]; p=0·084). At the third interim analysis (median follow-up 38·4 months [IQR 29·5-44·4] in the pembrolizumab group and 38·6 months [30·2-44·4] in the placebo group), median progression-free survival was 10·0 months (8·6-12·2) versus 8·1 months (7·1-8·6; HR 0·73 [0·61-0·87]), and median overall survival was 20·0 months (17·8-22·1) versus 16·8 months (15·0-18·7; HR 0·84 [0·70-1·01]), but did not meet prespecified criteria for significance and will continue to final analysis. Grade 3 or worse treatment-related adverse events occurred in 204 (58%) of 350 patients in the pembrolizumab group versus 176 (51%) of 346 patients in the placebo group. Treatment-related adverse events that led to death occurred in four (1%) patients in the pembrolizumab group and three (1%) in the placebo group. The most common treatment-related adverse events of any grade were diarrhoea (165 [47%] in the pembrolizumab group vs 145 [42%] in the placebo group), nausea (154 [44%] vs 152 [44%]), and anaemia (109 [31%] vs 113 [33%]). INTERPRETATION: Compared with placebo, pembrolizumab significantly improved progression-free survival when combined with first-line trastuzumab and chemotherapy for metastatic HER2-positive gastro-oesophageal cancer, specifically in patients with tumours with a PD-L1 combined positive score of 1 or more. Overall survival follow-up is ongoing and will be reported at the final analysis. FUNDING: Merck Sharp & Dohme.

The value of pretreatment glucose-to-lymphocyte ratio for predicting survival of metastatic gastric cancer.

Aim: To demonstrate the prognostic importance of glucose-to-lymphocyte ratio (GLR) in metastatic gastric cancer (mGC). Methods: Retrospectively, 159 mGC patients were enrolled. Kaplan-Meier curve and Cox regression analysis were used to determine the prognostic value of the systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI) and GLR. Results: Progression-free survival (PFS) and overall survival (OS) were associated with NLR, PNI, SII and GLR by univariate analysis. Moreover, OS was associated with Eastern Cooperative Oncology Group performance status and the chemotherapy regimen. In multivariate analysis, only GLR was found to be independently prognostic for both PFS and OS. Conclusion: In mGC, GLR may be a new prognostic marker for both OS and PFS.

Gastric cancer (GC) is the fourth cause of cancer-related deaths. Although different treatment algorithms, including immunotherapy, are applied in patients with unresectable or disseminated (metastatic) GC (mGC), survival results are not yet at the desired level. Different markers are being investigated to measure the response of cancer to treatment in these patients. Many studies have been conducted in this direction with the thought that the prognosis of these cancers will be affected by the patient's own immune response and nutritional status. Despite this, standard markers have not been established to predict cancer-related survival. Studies have shown a relationship between GC and glucose metabolism processes. Recently, a fasting blood glucose-to-lymphocyte count ratio (GLR) marker was developed that simultaneously evaluates both glucose metabolism and the patient's immune response. GLR was found to be effective in predicting survival time in cancers such as gallbladder cancer and hepatocellular carcinoma. However, the effect of GLR on survival in mGC is unclear. In this study, the authors investigated the prognostic significance of GLR in mGC. They found that low GLR was associated with longer survival in mGC. GLR may be a prognostic marker for survival in patients with mGC.

Lipegfilgrastim may cause hyperleukocytosis.

INTRODUCTION: Granulocyte colony-stimulating factors (G-CSF) are utilized both in the treatment and prophylaxis of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting G-CSF. Albeit it provides ease of administration compared to short-acting GCSFs, some lipegfilgrastim-related adverse events may occur. Bone pain, widespread body pain, and feeling of fever are among common adverse effects, while rare but more serious adverse effects such as leukocytosis, spleen rupture, interstitial pneumonia, acute respiratory distress syndrome, capillary leak syndrome, hypokalemia, and glomerulonephritis may occur as well. CASE REPORT: We reported a case of hyperleukocytosis that developed due to prophylactic administration of lipegfilgrastim following the first course of neoadjuvant pertuzumab (840-420 mg), trastuzumab (8-6mg/kg), and docetaxel (75 mg/m2) in a 45-year-old female patient with a diagnosis of breast invasive ductal carcinoma. The patient, who presented with weakness, loss of appetite, and oral intake disorder, had elevated white blood cell (WBC), lactate dehydrogenase (LDH), and uric acid levels in her test results. Peripheral smear (PS) had a left shift. MANAGEMENT AND OUTCOME: Intravenous 0.9% NaCl and peroral allopurinol were started to be administered to the patient. On the ninth day of hospitalization, the patient's clinical manifestation improved, and her WBC, LDH, uric acid, and PS returned to normal. Besides, the progression to tumor lysis syndrome (TLS) was prevented by appropriate hydration and allopurinol treatment. In subsequent chemotherapies (CTs), lipegfilgrastim was discontinued and filgrastim was started. The patient whose hyperleukocytosis did not recur was operated on following neoadjuvant CT. The patient's routine follow-up continues without any problems. DISCUSSION: Although lipegfilgrastim-induced hyperleukocytosis has not been reported in the literature, it should be borne in mind that hyperleukocytosis and related complications may occur, as in our case.

A novel prognostic biomarker for cutaneous malignant melanoma: red cell distribution width (RDW) to lymphocyte ratio.

It is well-known that inflammation plays a significant role in cancer formation and prognosis. Both lymphocyte count and red cell distribution width (RDW) has been used to predict prognosis in various cancers as an indicator of inflammation. Yet, the role of RDW-lymphocyte ratio (RLR) in determining prognosis is still unknown. We aimed to determine the prognostic role of RLR in cutaneous malignant melanoma (MM). One hundred fifteen patients with MM were included in the study retrospectively. The relationship of the clinical-pathological data with overall survival (OS) and progression-free survival (PFS) was analyzed using Kaplan-Meier curves. The cut-off values of neutrophil to lymphocyte ratio, systemic immune-inflammation index (SII), prognostic nutritional index (PNI) and RLR were determined as 2, 487, 51.5 and 6.52, respectively. OS was significantly longer in the low SII, high PNI, low RLR group, while PFS was longer in groups with high PNI and low RLR. In univariate analysis, it was determined that PFS was significantly correlated with Eastern Cooperative Oncology Group (ECOG) performance, TNM stage, PNI and RLR. Moreover, in univariate analysis, a significant correlation was determined between OS and age, ECOG performance, TNM stage, adjuvant interferon, SII, PNI and RLR. In multivariate analysis, ECOG performance, TNM stage and RLR were determined as independent prognostic factors for PFS, while TNM stage and RLR were found to be independent prognostic factors for OS. RLR could be a novel prognostic marker for both PFS and OS in patients with cutaneous MM.

The importance of the glucose-to-lymphocyte ratio in patients with hepatocellular carcinoma treated with sorafenib.

Aim: To show the prognostic significance of the glucose-to-lymphocyte ratio (GLR) in hepatocellular carcinoma (HCC). Patients & methods: A total of 150 patients with advanced HCC who were treated with sorafenib in our center between January 2011 and December 2019 were included in the study retrospectively. Neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index and GLR were analyzed to assess their prognostic value using Kaplan-Meier and Cox regression analysis before and after propensity score matching (PSM). Results: In univariate analysis before and after PSM, albumin-bilirubin grade, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, prognostic nutritional index, AFP level and GLR were found to be significantly associated with both progression-free and overall survival. In multivariate analysis before and after PSM, GLR, albumin-bilirubin grade and AFP were determined to be independent prognostic factors for progression-free and overall survival. Conclusion: The GLR prior to sorafenib treatment is a new prognostic biomarker that may predict survival in advanced HCC.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

PURPOSE: We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). METHODS: Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. RESULTS: Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). CONCLUSION: In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

Pazopanib for metastatic soft-tissue sarcoma: A multicenter retrospective study.

PURPOSE: Soft tissue sarcomas are associated with a poor prognosis and low chemotherapeutic efficiency. Pazopanib is an orally available multi-tyrosine kinase inhibitor that was explored in patients with non-adipocytic advanced soft tissue sarcomas. The aim of this retrospective study was to evaluate the real life data of single-agent pazopanib efficacy and safety for soft tissue sarcomas in the Turkish population. MATERIALS AND METHODS: We evaluated a total of 103 patients (41 males, 62 females) who received pazopanib for advanced non-adipocytic soft tissue sarcomas diagnosis in eight centers of Turkey, retrospectively. The pazopanib dose was 800 mg once daily. Progression-free survival, overall survival, and adverse events were analyzed. RESULTS: The median age was 50 years (range, 38-58). Majority of the patients had leimyosarcoma (41%). Median progression-free survival was 4.3 months, and the median overall survival was 10.1 months. The main common toxicities were fatigue, anorexia, weight loss, nausea, hypertension, and grade ≥3 toxicities were fatigue, anorexia, weight loss, and liver disorder. CONCLUSION: Pazopanib is an efficient and tolerable agent and is well tolerated in good performance status patients with relapsed, advanced non-adipocytic soft tissue sarcomas.

The prognostic significance of hemoglobin-to-red cell distribution width ratio in muscle-invasive bladder cancer.

Aim: To investigate the prognostic significance of pretreatment hemoglobin (HB)-to-red cell distribution width (RDW) ratio (HRR) in patients with muscle-invasive bladder cancer (MIBC). Materials & methods: The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), prognostic nutritional index, HRR, HB and RDW were analyzed to assess their prognostic value using the Kaplan-Meier curves and Cox-regression analysis in 152 patients with MIBC. Results: Univariate analysis showed that the progression-free survival (PFS) was associated with NLR, SII, HRR, RDW, whereas overall survival (OS) was associated with NLR, SII, prognostic nutritional index, HRR, HB, RDW. In multivariate analysis, HRR was found to be an independent prognostic factor for both PFS and OS. Conclusion: HRR is a new prognostic factor that can be used to predict PFS/OS in MIBC.

The Significance of Controlling Nutritional Status (CONUT) Score as a Novel Prognostic Parameter in Small Cell Lung Cancer.

PURPOSE: The immuno-nutritional status is closely related to the prognosis in many cancers. Controlling nutritional status (CONUT) score is a new parameter that reflects the immuno-nutritional status and is prognostic in some cancers. However, the prognostic significance of the CONUT score in small cell lung cancer (SCLC) is unknown. We aimed to demonstrate the prognostic significance of the CONUT score in patients with SCLC. METHODS: Two hundred sixteen patients who were followed up with SCLC were included in the study retrospectively. According to the receiver operating characteristic (ROC) curve analysis, the optimal cutoff values were determined for the CONUT score, and the patients were divided into low (< 2) and high (≥ 2) CONUT groups. Neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI) were grouped based on a cutoff point 2.84, 626, and 46.1, respectively. Cox regression analyses were used to assess their prognostic values for progression-free survival (PFS) and overall survival (OS). RESULTS: The high CONUT group had significantly worse PFS and OS than the low CONUT group (p < 0.001, p < 0.001). In univariate analysis, stage, prophylactic cranial irradiation, extrapulmonary lesion, PNI, body mass index, CONUT score were found to be significant for both PFS and OS. In multivariate analysis, only CONUT score and stage were found as independent prognostic factors for both PFS (p: 0.018, p: 0.046) and OS (p: 0.038, p: 0.006). CONCLUSION: The CONUT score at the time of diagnosis is an independent prognostic parameter that predicts recurrence and survival times in SCLC.

ERCC2 Lys751Gln rs13181 and XRCC2 Arg188His rs3218536 Gene Polymorphisms Contribute to Subsceptibility of Colon, Gastric, HCC, Lung And Prostate Cancer.

PURPOSE: Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. The relationship between genetic polymorphisms and cancer risk has been extensively researched. In the present study, we evaluated the association between polymorphisms in two DNA repair genes, ERCC2 Lys751Gln (rs13181) and XRCC2 Arg188His (rs3218536) and the risk of colorectal, stomach, HCC, prostate and lung cancer. METHODS: This study was planned by the Medical Biology Unit and Department of Internal Medicine, Pathology and Surgical Medicine Sciences of Ataturk University. A total of 40 colon cancer, 40 gastric cancer, 40 hepatocellular carcinoma (HCC), 40 prostate cancer, and 40 lung cancer patients and 40 healthy individuals over 18 years of age were enrolled in the study (Controls). All patients and healthy subjects underwent ERCC2 Lys751Gln rs13181 and XRCC2 Arg188His rs3218536 genotyping. After collection of 10 ml venous blood from the patients, DNA was isolated and single nucleotide polymorphism (SNP) analysis was performed using Roche 480 Real-Time PCR device. Results were analyzed using SPSS version 23.0 software. RESULTS: There were statistically significant differences in ERCC2 Lys751Gln rs13181 polymorphism variants GG colon and GT in the colon control and GG,TTprostate cancer groups when compared with the control group.. GG variant of XRCC2 Arg188 rs3218536 was higher in the gastric patient group. AG variant of XRCC2 Arg188 rs3218536 was higher in gastric control group Conclusion: The results of the present study demonstrate that ERC22 Lys751Gln polymorphisms may be associated with the development of colon and prostate cancers in the Turkish population. This was a small-scale study, and the results should be corroborated with further research including larger groups of patients with each cancer type and more healthy controls.

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia.

INTRODUCTION: The immune checkpoint inhibitors (ICIs), which are used to activate the immune system and stimulate anti-tumor activity, are preferred in many cancers. Atezolizumab acts by blocking programmed cell death ligand (PD-L1) and may cause immune hyperstimulation in healthy tissues like other ICIs, resulting in immune-related adverse events (irAEs). Hepatitis, colitis, pneumonitis, hypophysitis, hypothyroidism, rash, musculoskeletal problems are the most common irAEs, and on the other hand, acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP) are infrequent. CASE REPORT: We present a case with non-small cell lung cancer (NSCLC) treated with atezolizumab 1200 mg every three weeks for third-line treatment. The patient was admitted with fatigue and back pain. The patient's complaints started one week after the first dose of atezolizumab. The patient had renal injury and thrombocytopenia and was diagnosed with drug-induced AKI and ITP. MANAGEMENT AND OUTCOME: After platelet replacement, intravenous immunoglobulin (IVIG), and steroid therapy, the patient whose platelet count was normalized and creatinine level regressed was discharged, and routine follow-up continues. DISCUSSION: Here, we present a case with NSCLC treated with atezolizumab and with drug-induced ITP and AKI association. Given that atezolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the irAEs, including the AKI and ITP.

The ratio of hemoglobin to red cell distribution width predicts survival in patients with gastric cancer treated by neoadjuvant FLOT: a retrospective study.

BACKGROUND: Hemoglobin (HB) and red cell distribution width (RDW) are known to be prognostic in many cancer types. The HB-RDW ratio (HRR) is a new biomarker that has been shown to be predictive in some cancer types. However, the prognostic significance of HRR in patients with gastric cancer (GC) is unknown. AIMS: In this study, we aimed to demonstrate the prognostic importance of HRR in GC patients treated with neoadjuvant fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT). METHODS: Eighty-five GC patients who were treated with neoadjuvant FLOT in our center were included in the study, retrospectively. Associations between clinical and histopathological parameters with disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. Neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and HRR were grouped based on a cutoff points 3.05, 802, and 0.89, respectively. Univariate and multivariate analyses were used to assess their prognostic values for DFS and OS. RESULTS: Low NLR, low SII, and high HRR were found to be associated with longer DFS/OS. In univariate analysis, Eastern Cooperative Oncology Group performance status, grade, stage, response to neoadjuvant treatment, NLR, SII, and HRR were found to be significantly associated with DFS and OS. But in multivariate analysis, only HRR was demonstrated as an independent prognostic factor for DFS/OS (p 0.001, p 0.037, respectively). CONCLUSIONS: HRR is a new biomarker that can predict DFS and OS in GC patients treated with neoadjuvant FLOT.

Colorectal cancer in Lynch syndrome associated with PMS2 and MSH6 mutations.

BACKGROUND: It is known that colorectal cancers (CRC) are frequently seen and constitute an important part of cancer-related deaths. Lynch syndrome (LS) is responsible for 3-5% of CRCs and develops due to mutations in DNA mismatch repair (MMR) genes. The most important MMR genes are MutL homolog1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6) and postmeiotic segregation increased 2 (PMS2). PMS2 and MSH6 mutations are very rarely seen in LS. CASE PRESENTATION: We present a case that developed metastatic CRC, which we diagnosed as LS in association with a very rarely seen PMS2 and MSH6 germline mutation. Genetic counseling was recommended for the family, and screening programs were initiated for the family of the patient whose chemotherapy was continued after the diagnosis. CONCLUSION: With the increase in daily use of next-generation sequencing (NGS) technology, it is thought that detection rate of both combined mutations and rare mutations will be increased.

A novel predictor in patients with gastrointestinal stromal tumors: Systemic immune-inflammation index (SII).

PURPOSE: Systemic inflammation and immune response are associated with tumors'prognosis. However, there is little information about inflammatory indexes in patients with gastrointestinal stromal tumor (GIST). In this study, we aimed to determine the prognostic significance of inflammation indexes such as neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI) and Glasgow prognostic score (GPS) in GIST patients. METHODS: Forty-five patients diagnosed with GIST between 2003 and 2018 were included in the study. The effects of NLR, SII, PNI and GPS on progression-free survival (PFS) and overall survival (OS) estimated based on clinicopathological and laboratory data were evaluated by Kaplan-Meier and Cox regression analysis. RESULTS: The optimal cut-off values for NLR, SII and PNI were 2.54, 940, and 37.5, respectively. Low SII and higher PNI values were associated with longer PFS (p=0.041, p=0.018, respectively). In terms of OS, patients with high NLR, high SII and low PNI had a shorter lifespan. In multivariate analysis, only SII was found to be independent prognostic factor. CONCLUSION: In cases with GIST, SII may predict recurrence and survival.

Clinicopathologic and Prognostic Differences between Three Different Age Groups (Child/Adolescent, Young Adults, and Adults) of Colorectal Cancer Patients: A Multicentre Study.

BACKGROUND: Colorectal cancer (CRC) is a rare disease amongst children and adolescents. Previous studies have reported a number of differences between children/adolescents, young adults, and adult patients with CRC. However, none of these studies compared these age groups according to their clinicopathologic and prognostic characteristics. In the current study, we compare these three age groups. METHODS: A total of 173 (1.1% of 15,654 patients) young CRC patients (≤25 years) were included in the study. As a control group, 237 adult CRC patients (>25 years) were also included. Patients were divided into three age groups: child/adolescent (10-19 years), young adult (20-25 years), and adult (>25 years). RESULTS: Statistical differences amongst the three groups in terms of gender (p = 0.446), family history (p = 0.578), symptoms of presentation (p = 0.306), and interval between initiation of symptoms and diagnosis (p = 0.710) could not be demonstrated. Whilst abdominal pain (p < 0.001) and vomiting (p = 0.002) were less common in young adults than in other groups, rectal bleeding and changes in bowel habits were relatively less common in adolescents than in other groups. Rectal localisation (p = 0.035), mucinous adenocarcinoma (p < 0.001), and a poorly differentiated histologic subtype (p < 0.001) were less common in the adult group than in other groups. The percentage of patients with metastasis and sites of metastasis (e.g., peritoneum and lung) differed between groups. The median overall survival was 32.6 months in the adolescent group, 57.8 months in the young adult group and was not reached in the adult group (p = 0.022). The median event-free survival of the adolescent, young adult, and adult groups was 29.0, 29.9, and 61.6 months, respectively (p = 0.003). CONCLUSIONS: CRC patients of different age groups present different clinicopathologic and prognostic characteristics. Clinicians should be aware of and manage the disease according to these differences.

Relationship between 18-FDG-PET/CT and Clinicopathological Features and Pathological Responses in Patients with Locally Advanced Breast Cancers.

OBJECTIVE: We investigated the relationship between the maximum standardized uptake value (SUVmax) of whole-body positron emission tomography/computed tomography (PET/CT) performed before treatment and the demographical and histopathological features in locally advanced breast cancer (LABC), as well as the role of PET/CT in the evaluation of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Fifty-one LABC patients who received NAC in our center between 2011 and 2015 were retrospectively analyzed. Basal PET/CT was performed in all the patients before NAC. The SUVmax levels and demographical and histopathological results were compared. The relationship between the SUVmax values after NAC and pathological responses were evaluated. RESULTS: The mean age of the patients was 49 (32-69) years. PET/CT performed after NAC showed complete response in 20 patients (39.2%), partial response in 28 patients (54.9%), stable disease in 2 patients (3.9%), and progressive disease in 1 patient (2%). There was no significant difference between the mean SUVmax values of the patients according to age (>50 and ≤50 years), menopausal status, tumor localization, clinical stage, and grade. The mean SUVmax value was higher in the triple-negative group than those in the HER2 positive and luminal groups. There was a significant difference in the SUVmax values between the group that achieved pCR after NAC and the group that could not achieve pCR (SUVmax value for breast 2.92 vs. 0.30; p=0.01; SUVmax value for axilla 1.5 vs. 0.0, p=0.02). CONCLUSION: The SUVmax values are independent of demographical features. There was a significant relationship between the pCR and SUVmax values after NAC. PET/CT could be useful in the evaluation of patients to predict the biological characteristics of tumors.