Clinicopathological and survival features of neuroendocrine tumors: A retrospective analysis of 153 cases, our current remarks on a heterogeneous tumor group, and still unmet future expectations.

Objective: Neuroendocrine neoplasms (NENs) originate from the diffuse neuroendocrine cell system and constitute a heterogeneous group of tumors exhibiting diverse clinical and biological characteristics. NENs include well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). In the present study, we performed a retrospective analysis of patients diagnosed with NET to evaluate clinicopathological characteristics, treatment and outcomes. Material and Methods: Data from 153 patients diagnosed with NET who were treated and followed up at three tertiary care centers from November 2002 to June 2021 were retrospectively evaluated. Clinicopathological and prognostic factors, treatment modalities and survival data were analyzed. Kaplan-Meier analysis was used to assess survival data and comparisons were performed using the logrank test. Results: Median age (IQR) was 53 (18-80) years. 85.6% of the patients had gastro-entero-pancreatic (GEP)-NET. The primary tumor was resected in 95 patients (62.1%) and metastasectomy were performed in 22 patients (14.4%). Seventy-eight patients received systemic therapy for metastatic disease. Patients were followed up for a median of 22 (IQR = 33.8) months. The estimated one-year and three-year survival rate was 89.8% and 74.4%, respectively. Median progression-free survival (PFS) were 10.1, 8.5, and 4.2 months after first-, second- and third-line therapy, respectively. Conclusion: The number of systemic treatment options and diagnostic tools for NETs has significantly improved in the last few years. NET classification, which treatment will be more appropriate for which group of patients, the molecular basis of this disease and the development of treatment strategies are open-ended questions that still need to be investigated.

Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, neutrophil-platelet score and prognostic nutritional index: do they have prognostic significance in metastatic pancreas cancer?

INTRODUCTION: We aimed to evaluate the prognostic significance of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet score (NPS) and prognostic nutritional index (PNI) as proinflammatory markers in metastatic pancreas cancer (MPC). MATERIAL AND METHODS: A total of 146 MPC patients followed up at our center were evaluated retrospectively for clinicopathological characteristics and hematological ratios (NLR, PLR, NPS and PNI). PNI was calculated as (10 × serum albumin [g/dL]) + (0.005 × peripheral lymphocyte count [per mm³]). Log rank and Cox regression analysis were used. RESULTS: Median age was 53 years (range: 22-78) with male predominance (73.3%). Liver (94.7%) was the most common site for metastasis. Half (53.4%) of the patients had ECOG-PS <2; 18% had cholestasis. Palliative chemotherapy predominantly gemcitabine was given to 86.3% of the patients. Clinical benefit rate was 58.2% and objective response rate (ORR) was 23%. Median overall survival (OS) and progression-free survival (PFS) were 6.3 months (95% CI: 5.2-7.8) and 4.9 months (95% CI: 3.6-6.1). Age (p = .003), ECOG-PS (p = .0001), palliative chemotherapy (p = .002), cholestasis (p = .001) and NLR (p = .001) were statistically significant but PLR (p = .062), NPS (p = .86) and PNI (p = .51) were not significant in univariate analysis. Age (HR 1.026, 95% CI: 1.007-1.045, p = .007), ECOG-PS (HR 0.299, 95% CI: 0.202-0.443, p = .0001), cholestasis (HR 0.541, 95% CI: 0.325-0.901, p = .01) and NLR (HR 1.076, 95% CI: 1.025-1.130, p = .003) were significant prognostic factors in multivariate analysis. CONCLUSIONS: Basal high NLR (>3), advanced age (>60 years), poor ECOG-PS (>2) and cholestasis were independent poor prognostic factors in MPC. However, PNI, NPS and PLR had no prognostic significance (p = .51, p = .86 and p = .062, respectively).

Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio associated with prognosis in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab?

PURPOSE: To investigate whether the pretreatment neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) have any prognostic significance in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab. METHODS: 187 patients were retrospectively analyzed. The patients were separated into two groups according to the mean value of NLR and PLR (low NLR≤2.38, high NLR>2.38; and low PLR≤161.28, high PLR>161.28, respectively). The relationship between pretreatment NLR, PLR and clinicopathological factors was investigated. Univariate and multivariate Cox regression analyses were performed. To evaluate survival rates, the Kaplan-Meier method with log rank test were used. RESULTS: The median duration of follow up was 26.0 months (range 6.0-84.0). In high NLR and PLR groups, the mean age was lower, tumor size was larger and the number of hormone receptor positive patients was higher. No statistically significant relationship was found between clinicopathological factors and both NLR and PLR groups. During follow up, the rate of relapse was 12.6% in the low NLR group, 16.2 % in the high NLR group, 12.6% in the low PLR group and 15.8% in the high PLR group (p=non significant). Although median disease free survival (DFS) was shorter in the high NLR than in the low NLR group, the difference was not statistically significant (p=0.45). No statistically significant difference was found between high and low PLR groups with regard to median DFS and overall survival (OS) (p=0.76, p=0.29, respectively). CONCLUSION: We conclude that in HER2-positive early breast cancer patients receiving adjuvant trastuzumab with high pretreatment NLR, DFS was shorter. As for PLR, no effect either on DFS or on OS was registered. Prospective studies with larger number of patients are required in order to evaluate the prognostic effect of NLR and PLR in HER2-positive breast cancer patients.

Patients with HER2-positive early breast cancer receiving adjuvant trastuzumab: clinicopathological features, efficacy, and factors affecting survival.

BACKGROUND: The aim of the present study was to evaluate clinicopathological characteristics of our early stage breast cancer patients who are epidermal growth factor receptor 2 (HER2) overexpressed/ amplified (HER2+), the efficacy of trastuzumab treatment and survival results. MATERIALS AND METHODS: Patients with HER2- positive early stage breast cancer receiving adjuvant trastuzumab were investigated retrospectively. Clinicopathological features of 210 patients and treatment outcome were analysed. To evaluate survival rates, the Kaplan-Meier method was used. Univariate and multivariate analyses were conducted with the Cox regression model. RESULTS: Mean age of the patients was 51.8, 71.9% being postmenopausal. Some 37.6% of patients were node negative, and 31% had T1 tumor size and 52.4% were positive for estrogen receptor. Of 210 patients, 89.5% completed planned 52 weeks adjuvant trastuzumab treatment. The median follow up was 27.5 months (6.0-86.0 ). Relapse free survival (RFS) was 68.0 months (95% CI: 62.1-74.0) and overall survival (OS) was 74.8 months (95% CI: 69.5-80.1). The 3 year OS for all patients was 92.0% and RFS was 79.6%. During follow up, relapse was detected at the rate of 14.3%. Trastuzumab associated cardiotoxicity was found at the rate of 3.3%. In univariate analyses, larger tumor size and grade III were significantly associated (p<0.05) with RFS. Multivariate analyses of covariates displaying p<0.05 identified grade III as an independent prognostic factor. CONCLUSIONS: In the present study, it was established that trastuzumab had a satisfactory safety profile and treatment efficacy as in other clinical studies and that among clinicopathological factors evaluated, only being grade 3 had a significant effect on RFS. The occurrence of relapse with adjuvant trastuzumab makes it necessary to identify molecular predictors, which will define this group better and help explain resistance to anti HER2 based therapies.

Hypersensitivity and tumor lysis syndrome associated with cetuximab treatment: should we be afraid?

The majority of the chemotherapy agents in use today cause various infusion reactions, from mild flushing to life-threatening events. The frequency of the reported hypersensitivity reactions induced by cetuximab varies between 3% and 22%. It is recommended in the literature to stop the infusion and replace cetuximab with panitumumab in case of hypersensitivity reactions observed during the treatment of colon cancer. Tumor lysis syndrome (TLS) may occur in colorectal cancers with heavy tumor load. Tumor lysis syndrome may be life-threatening. In our patient with widespread bone and liver metastases, treatment continued with cetuximab as a combination therapy with irinotecan in spite of the hypersensitivity and TLS led to a complete treatment response. The complete response observed after 3 months through continued therapy in our patient may present an example supporting treatment with cetuximab in spite of severe reactions.

Prognostic factors and adjuvant treatments for surgically treated cancers of the biliary tract: a multicentre study of the Anatolian Society of Medical Oncology (ASMO).

BACKGROUND: Biliary tract cancers are rare, and surgical resection is the standard treatment at early stages. However, reports on the benefits of adjuvant treatment following surgical resection are conflicting. This study aimed to evaluate the factors affecting survival and adjuvant treatments in patients with surgically treated biliary tract cancers. MATERIALS AND METHODS: Patient clinical features, adjuvant treatments, and efficacy and prognostic factor data were evaluated. Survival analyses were performed using SPSS 15.0. RESULTS: The median overall survival was 30.7 months (95% confidence interval [CI], 18.4-42.9 months). Median survival was 19 months (95% CI, 6-33) for patients treated with fluorouracil based chemotherapy and 53 months (95% CI, 33.2-78.8) with gemcitabine based chemotherapy (p=0.033). On univariate analysis, poor prognostic factors for survival were galbladder localization, perineural invasion, hepatic invasion, a lack of adjuvant chemoradiotherapy treatment, and a lack of lymph node dissection. On multivariate analysis, perineural invasion was a poor prognostic factor (p=0.008). CONCLUSIONS: Biliary tract cancers generally have poor prognoses. The main factors affecting survival are tumour localization, perineural invasion, hepatic invasion, adjuvant chemoradiotherapy, and lymph node dissection. Gemcitabine-based adjuvant chemotherapy is more effective than 5-fluorouracil-based chemotherapy.

Serum 25-hydroxy vitamin D status is not related to osteopenia/osteoporosis risk in colorectal cancer survivors.

BACKGROUND: The incidence of colorectal cancer increases with vitamin D deficiency as shown in recently published studies. In addition, prospective investigations have indicated that low vitamin D levels may be associated with increased mortality of colorectal cancer, especially in stage III and IV cases. However, the exact incidence of vitamin D deficiency and the relation between vitamin D deficiency and osteopenia/osteporosis is still not known. The aim of this study is to identify severity of vitamin D deficiency and absolute risk factors of osteopenia/osteoporosis in colorectal cancer survivors. MATERIALS AND METHODS: A total of 113 colorectal cancer survivors treated with surgery and/or chemotherapy ± radiotherapy were recruited from medical oncology outpatient clinics during routine follow-up visits in 2012-2013. Bone mineral densitometry (BMD) was performed, and serum 25-OH vitamin D levels were also checked on the same day of the questionnaire. The patients was divided into 2 groups, group A with normal BMD and group B with osteopenia/osteoporosis. RESULTS: The median age of the study population was 58 (40-76). Thirty (30.0%) were female, whereas 79 (70.0%) were male. The median follow-up was 48 months (14-120 months). Vitamin D deficiency was found in 109 (96.5%); mild deficiency (20-30 ng/ml) in 19 (16.8%), moderate deficiency (10-20 ng/ml) in 54 (47.8%) and severe deficiency (<10 ng/ml) in 36 (31.9%). Osteopenia was evident in 58 (51.4%) patients whereas osteoporosis was noted in 17 (15.0%) . Normal BMD was observed in 38 (33.6%). No apparent effects of type of surgery, presence of stoma, chemotherapy, radiotherapy and TNM stage were found regarding the risk of osteopenia and osteoporosis. Also, the severity of the vitamin D deficiency had no effect in the risk of osteopenia and osteporosis (p=0.93). In female patients, osteopenia/osteoporosis were observed in 79.5% patients as compared to 60.7% of male patients (p=0.04). CONCLUSIONS: In our study, vitamin D deficiency and osteopenia/osteoporosis was observed in 96.5% and 66.4% of colorectal cancer survivors, respectively. There is no defined absolute risk factor of osteopenia and osteoporosis in colorectal cancer survivors. To our knowledge, in the literature, our study is the first to evaluate all the risk factors of osteopenia and osteoporosis in colorectal cancer survivors.

Treatment and outcomes of Ewing sarcoma in Turkish adults: a single centre experience.

BACKGROUND: Ewing sarcoma is a small round cell tumor arising from soft tissue and bone that predominantly affects children and adolescents. The most unfavorable prognostic factor is the presence of distant metastasis at the time of diagnosis. MATERIALS AND METHODS: The records of 26 Ewing sarcoma patients (14 male, 12 female) were re-evaluated retrospectively. RESULTS: The median age was 26.5 (19-42) years. Eight patients (31%) showed a primary tumor in their extremities, 8 (31%) in the thorax, 4 (15%) at the vertebra, 4 (15%) in the head and neck, and 2 (8%) in the abdomen. Five patients (19%) had distant metastasis at diagnosis. The median progression-free survival was 72 months and 10 months in localized and metastatic disease, respectively (p=0.005). The overall survival rate was 19 months in metastatic disease, and the 5-year overall survival rate was 64% in localized disease (p=0.006). Patients who had localized disease in the extremities and were under age 30 had a favorable prognosis. CONCLUSIONS: Although Ewing sarcoma is a tumor affecting children and adolescents, it may be seen in adults, where the prognosis is generally worse. Although it is a highly malignant tumor, it is possible to achieve improved survival with combined modality treatments.

Results of adjuvant FOLFOX regimens in stage III colorectal cancer patients: retrospective analysis of 667 patients.

OBJECTIVE: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. METHODS: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. RESULTS: The median age of the patients was 56 years (range 17-78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1-79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. CONCLUSION: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.