Acute sunitinib neurotoxicity.

Sunitinib malate is a multitargeted oral tyrosine kinase inhibitor (TKI) which is used in treatment of metastatic renal cell carcinoma with side effects such as diarrhea, mucositis, asthenia and myelosuppression. Serious toxicity associated with sunitinib is a rare situation. However; there are few cases reported in the literature. As a result of the inhibition that is caused by sunitinib malate agent at the receptor level, vascular endothelial growth factor (VEGF) level increases. These increased VEGF levels are considered to having a positive contribution on neurological side effects. Neurotoxicity that is related with the usage of sunitinib malate for two weeks will be presented in this case report.

Why Adjuvant and Neoadjuvant Therapy Failed in HCC. Can the New Immunotherapy Be Expected to Be Better?

INTRODUCTION: HCC remains a challenging disease with its unique characteristics and aggressive behavior. Although there are some curative-intent treatments such as liver transplantation and surgical resection, they themselves did not cure the patients with relatively high recurrence rates. Several modalities including local ablation methods like TACE or TARE, systemic treatments such as chemotherapy, tyrosine kinase inhibitors or antiviral therapies are tested in adjuvant or neoadjuvant setting, but none of them offered a survival benefit (except antiviral therapy in HBV-related HCC). CONCLUSION: After a decade of plateau in drug development, ICPIs came into podium with their different mechanism of action consistent with immunogenic nature of the disease and with high expectations, and ongoing trials will show if these agents can satisfy unmet demand in this area.

Author Correction: Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria.

The original version of this article unfortunately contained a mistake in the author group section.

Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria.

Survival was examined from a Turkish liver transplant center of patients with HCC, to identify prognostic factors. Data from 215 patients who underwent predominantly live donor liver transplant for HCC at our institute over 12 years were included in the study and prospectively recorded. They were 152 patients within and 63 patients beyond Milan criteria. Patients beyond Milan criteria were divided into two groups according to presence or absence of tumor recurrence. Recurrence-associated factors were analyzed. These factors were then applied to the total cohort for survival analysis. We identified four factors, using multivariate analysis, that were significantly associated with tumor recurrence. These were maximum tumor diameter, degree of tumor differentiation, and serum AFP and GGT levels. A model that included all four of these factors was constructed, the 'Malatya criteria.' Using these Malatya criteria, we estimated DFS and cumulative survival, for patients within and beyond these criteria, and found statistically significant differences with improved survival in patients within Malatya criteria of 1, 5, and 10-year overall survival rates of 90.1%, 79.7%, and 72.8% respectively, which compared favorably with other extra-Milan extended criteria. Survival of our patients within the newly defined Malatya criteria compared favorably with other extra-Milan extended criteria and highlight the usefulness of serum AFP and GGT levels in decision-making.

A rare case Of gastric cancer: Isolated vaginal metastasis.

Gastric cancer is one of the most common cancers worldwide. The vast majority of gastric cancer is adenocarcinoma histologically. The majority of gastric cancer patients show distant metastasis at the time of diagnosis. Because they are diagnosed with metastatic disease, most often they are inoperable ovarian metastasis is a well-known metastasis of gastric cancer. Vaginal metastasis happens by the local spreading of ovarian or uterine metastasis. This study reports a gastric cancer case that presented with isolated vaginal metastasis in the absence of ovarian or uterine metastasis.

Survival and prognostic factors in patients with brain metastasis: Single center experience.

PURPOSE: The purpose of this study was to evaluate the clinical status, prognostic factors and treatment modalities affecting survival in patients with brain metastasis. We aimed to evaluate the whole brain radiation therapy (WBRT) outcomes of patients with brain metastasis in our center. METHODS: Clinical data of 315 patients referred to our center between 2004 and 2014 with metastatic brain cancers were collected and analysed for possible relationships between survival time, age, gender, Karnofsky performance status (KPS), recursive partitioning analysis (RPA), primary tumor, number of brain lesions, surgery, radiation therapy scheme, extracranial metastatic status and primary disease control status. RESULTS: The average patient age of onset was 58 years. The primary tumor site was lung (68%), breast (12%), melanoma (4%), colorectal (1.6%), sarcoma (1.3%) and unknown primary disease (4.4%). The rest of the patients had other primary sites. Eighty four (26.6%) patients had single brain metastasis, 71 (22.5%) had 2 or 3 lesions, and 159 (50.4%) patients had more than 3 lesions. Leptomeningeal involvement was seen in combination of paranchymal involvement in 11 (3.5%) patients. Fifty patients had undergone surgical resection. WBRT was delivered to all of the patients. Median overall survival was 6.7 months (95% CI, 5.80-7.74). Median overall survival of patients treated with combination of surgery and WBRT was significantly better compared with those treated with WBRT alone (13.5 vs 5.5 months, p=0.0001). One- and 2- year survival was 17 and 4.7%, respectively. CONCLUSIONS: The present study concludes that brain metastasis is common in cancer patients. The best overall survival was obtained by surgery+NBRT in good-condition patients. Treatment should be tailored on an individual basis to all these patients.

Modified docetaxel and cisplatin in combination with capecitabine (DCX) as a first-line treatment in HER2-negative advanced gastric cancer.

BACKGROUND: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. MATERIALS AND METHODS: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel 60 mg/m2 plus cisplatin 60 mg/m2 (day 1) combined with capecitabine 1650 mg/m2 (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. RESULTS: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. CONCLUSIONS: DCX regimen offers prominent anti-tumor activity and considered to be effective first- line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.

Positive effects of oral ß-glucan on mucositis and leukopenia in colorectal cancer patients receiving adjuvant FOLFOX-4 combination chemotherapy.

The present study aimed to determine the effect of oral ß-glucan on mucositis and leukopenia in 62 consecutive patients with colorectal cancer treated with an adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2 groups: one group received ß-glucan and the other did not (control group). Leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil counts after chemotherapy in the ß-glucan group were 7,300/mm3 and 3,800/mm3, respectively, and the reductions, as compared to baseline, were not significant (p=0.673 and 0.784). The median platelet count was 264,000/mm3 after chemotherapy in the ß-glucan group and the reduction, as compared to baseline, was borderline significant (p=0.048). In the control group, reduction in leucocyte, neutrophil, and platelet counts was statistically significant. Oral mucositis and diarrhea were less common in the ß-glucan group. We conclude that ß-glucan can be used to reduce the adverse effects of chemotherapy.

Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer.

OBJECTIVES: To evaluate treatment results and toxicities in patients who received concomitant chemoradiotherapy (CRT) followed by consolidation with docetaxel and cisplatin in locally advanced unresectable non-small cell lung cancer (NSCLC). METHODS: Ninety three patients were included in this retrospective study. The patients received 66 Gy radiotherapy and weekly 20 mg/m(2) docetaxel and 20 mg/m(2) cisplatin chemotherapy concomitantly. One month later than the end of CRT, consolidation chemotherapy with four cycles of docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) were administered at each 21 days. RESULTS: Median age of the patients was 57 (range, 30-74). Following concomitant CRT, 14 patients (15%) showed complete and 50 patients (54%) showed partial response (total response rate was 69%). The median follow-up was 13 months (range: 2-51 months). The median overall survival was 18 months (95% confidential interval [CI]: 13.8-22.1 months); local control was 15 months (95% CI: 9.3-20.6 months); progression-free survival was 9 months (95% CI: 6.5-11.4 months). Esophagitis in eight (9%) patients, neutropenia in seven (8%) patients and pneumonitis in eight (9%) patients developed as grade III-IV toxicity due to concomitant CRT. CONCLUSION: Concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC.

Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study.

BACKGROUND: We aimed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients. METHODS: In this small, prospective, double-blind study, we randomly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive nebivolol 5mg daily (n=27) or placebo (n=18). Echocardiographic measurements and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were obtained at baseline and at 6-month of chemotherapy. RESULTS: Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline. At 6-month, the left ventricular (LV) end-systolic and end-diastolic diameters increased in the placebo group (LVESD: 29.7 ± 3.4 to 33.4 ± 4.5mm; LVEDD: 47.2 ± 3.8 to 52.0 ± 4.6mm, p=0.01 for both) but remained unchanged in the nebivolol group (LVESD: 30.4 ± 3.5 to 31.0 ± 3.6mm, p=0.20; LVEDD: 47.0 ± 4.4 to 47.1 ± 4.0mm, p=0.93). The placebo group also had lower LVEF than the nebivolol group (57.5 ± 5.6% vs. 63.8 ± 3.9%, p=0.01) at 6-month. NT-pro-BNP level remained static in the nebivolol group (147 ± 57 to 152 ± 69 pmol/l, p=0.77) while it increased in the placebo group (144 ± 66 to 204 ± 73 pmol/l, p=0.01). CONCLUSIONS: Prophylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients.

Stomach metastasis in a patient with prostate cancer 4 years after the initial diagnosis: a case report and a literature review.

Prostate cancer commonly metastasizes bones and lymph nodes, but it very rarely spreads to the gastrointestinal tract. However, only five cases of prostate cancer metastatic to the stomach have been previously reported in the literature. We report a case of a 69-year-old man with metastatic prostate cancer who presented with upper gastrointestinal bleeding (UGB) 4 years after the diagnosis. Esophagogastroscopy revealed multiple ulcerations in the gastric body and histopathological examination confirmed gastric metastasis that originated from prostate cancer. Chemotherapy could not be given because of patient's refusal. He was treated with LHRH agonist. We suggest that for a man with prostate cancer diagnosed with UGB, stomach metastasis should be considered in the differential diagnosis of UGB.

Do thrombophilic gene mutations have a role on thromboembolic events in cancer patients?

AIM: Thromboembolism is common in patients with cancer and may be considered a major cause of morbidity and mortality. We studied the most common genetic polymorphism characteristics that may have roles in the development of thrombosis in patients with cancer. METHODS: A total of 158 patients with cancer who had had any thrombotic event were included, together with a control group of 134 patients with cancer without a thromboembolic event. The presence of mutations (Factor V Leiden G1691A, prothrombin G20210A) and polymorphisms (methylenetetrahydrofolate reductase [MTHFR] C677T and plasminogen activator inhibitor (PAI-1) 4G/5G) were analysed. RESULTS: A heterozygous polymorphism for Factor V Leiden G1691A was found in 48 patients (30.3%) and a homozygous polymorphism in only one (0.63%), compared to 32 heterozygous (23.8%) and one homozygous (0.74%) polymorphism in the control group (P = 0.462). Prothrombin G20210A heterozygous polymorphism was observed in 11(6.9%) and four (2.5%) in the patients and controls, respectively. The MTHFR C677T heterozygous polymorphism was found in 48 (30.3%) and 24 (15.1%) and the homozygous polymorphism was observed in 15 (9.4%) and 12 (7.5%) in the study and control group, respectively (P = 0.04). CONCLUSION: Although we found a statistically significant difference between patients with and without thrombosis in respect to MTHFR C677T gene mutation, our data suggest that we do not have enough evidence yet to recommend performing genetic analysis.

Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer.

PURPOSE: The efficacy and tolerability of bevacizumab every 2 or 4 weeks using the same dosage in combination with biweekly FOLFIRI were retrospectively evaluated in metastatic colorectal cancer (mCRC) patients in the first-line and second-line therapy. PATIENTS AND METHODS: A total of 332 patients from six centers were evaluated. The patients had received biweekly FOLFIRI in combination with bevacizumab 5 mg/kg every 2 weeks or every 4 weeks schedule for various reasons in individual patients. RESULTS: Approximately 70 % of all patients had 2-week treatment schedule. In the first-line therapy (n = 240), the overall response rate (ORR) was 34.1 % in 2-week and 36.3 % in 4-week groups. Median progression-free survival (PFS) was 8 months (95 %CI, 6.8-9.2) and 9 months (95 %CI, 6.6-11.4) (p = 0.074), and median overall survival (OS) was 22 months (95 %CI, 15.8-28.2) and 20 months (95 %CI, 8.1-31.9) (p = 0.612) in 2- and 4-week groups, respectively. One-year survival rate was 76.2 % for 2-week group and 73.2 % for 4-week group. In the second-line therapy (n = 92), the ORR was similar between the groups (24.5 vs 25.9 % in 2- and 4-week groups, respectively). Median PFS was 6 months (95 %CI, 4.7-7.3) and 11 months (95 %CI, 6.3-15.7) (p = 0.074), and median OS was 15 months (95 %CI, 9.6-20.4) and 17 months (95 %CI, 13.7-20.3) (p = 0.456) for 2-week and for 4-week groups, respectively. One-year survival rate was 61.3 % for 2-week and 71.3 % for 4-week groups. Toxicity profile was similar in 2- and 4-week groups and included neutropenia, febrile neutropenia, nausea and vomiting, diarrhea, mucositis, bleeding, hypertension, thromboembolism and fistulization. CONCLUSION: Bevacizumab 5 mg/kg every 2 weeks or every 4 weeks in combination with biweekly FOLFIRI had similar efficacy and tolerability in mCRC. Because of the retrospective nature of our study, the data should be examined cautiously. However, our study clearly points out the need for determination of optimum biological dosing interval of bevacizumab in well-designed, prospective, randomized trials.

Irinotecan as a second-line monotherapy for small cell lung cancer.

OBJECTIVES: The present study was designed to investigate the efficacy of irinotecan monotherapy as a second-line treatment for small cell lung cancers (SCLCs). METHODS: Irinotecan monotherapy was administered to 46 SCLC patients who were previously undergone cisplatin based chemotherapy protocols. Response to treatment, time to progression (TTP), overall survival rates and adverse events associated with irinotecan monotherapy (300mg/m2; total 153 cycles; mean 3.78 ∓ 1.98) were determined, retrospectively. RESULTS: Limited stage disease was diagnosed in 19.6% of patients (n=9) while 80.4% (n=37) were diagnosed with extensive stage cancer preceeding the irinotecan monotherapy. None of the patients had complete response to irinotecan. Partial response and stable disease were achieved among 17.5% of patients. Mean time to tumor progression (TTP) was determined to be 11.3±5.94 weeks while overall survival was 13.3±6.83 months. Considering adverse events, grade 3 and 4 toxicity was encountered in 8.9% and 4.5% of patients, respectively. Irinotecan monotherapy in brain metastasized tumors was found to be associated with significantly higher survival times compared with tumors lacking brain metastasis (15.0±5.95 vs 10.7±4.82 months; p< 0.05). CONCLUSIONS: Irinotecan as a monotherapy in the second-line treatment of SCLC seems to have an acceptable level of toxicity and significant palliative effects. The prominent survival step-up effect particularly in brain metastasis patients appears worthy of note.

Cyclooxygenase-2 expression in gastrointestinal stromal tumours.

BACKGROUND: While it is well known that cyclooxygenase-2 (COX-2) expression is increased in colorectal adenoma and carcinoma, there is only limited information on its status in stromal tumours. METHODS: Immunohistochemical COX-2 staining was performed on a total of 42 confirmed gastrointestinal stromal tumours (GISTs) in the Pathology Department of Gaziantep University and the findings were compared with various other parameters. RESULTS: We found a statistically significant correlation between the tumor mitosis and COX-2 expression in GISTs. However, there was no relationship between COX-2 expression and death rate, presence of metastasis, tumour size, risk staging, usage of tyrosine kinase inhibitors, and complete resection rate. CONCLUSIONS: In the light of these findings, the usage of COX-2 inhibitors with or without tyrosine kinase inhibitors in GIST patients may be helpful in the adjuvant setting to prevent or delay recurrence. Moreover, we need more studies to define the status of COX-2 inhibitors in GISTs.

Association between the Thr431Asn polymorphism of the ROCK2 gene and risk of developing metastases of breast cancer.

The objective of this study was to analyze the genotype distributions and allele frequencies for ROCK2 Thr431Asn and Arg83Lys polymorphisms among breast cancer patients. In this case-control study, 223 patients with breast cancer were recruited and divided into two groups according to metastases (n = 128) and without metastases (n = 95). Genomic DNA from the patients and the control cases (n = 150) was analyzed by real-time PCR using a Light-Cycler. Neither genotype distributions nor the allele frequencies for the Arg83Lys polymorphism showed a significant difference between the groups. Although no marked changes were observed with nonmetastatic group, a statistically significant association was found between the control and metastatic group for the Thr431Asn polymorphism. Although homozygous carriers of the Thr431Thr genotype were more frequent, heterozygous carriers of the Thr431Asn genotype were less frequent among the metastatic patients than among controls. There was also an increase in Thr431 allele (60.5% in patients vs. 51.7% in controls) and decrease in Asn431 allele frequencies (48.3% in control vs. 39.5% in metastatic patients) in metastatic groups (p = 0.036). Our results demonstrate that Thr431Asn polymorphism of the ROCK2 gene could be a risk factor for the metastases of the breast cancer, and may help in predicting the prognosis.

Prognostic value of excision repair cross-complementing gene 1 expression for cisplatin-based chemotherapy in advanced gastric cancer.

BACKGROUND: Association of excision repair cross-complementing gene 1 (ERCC1) expression and treatment response and survival was evaluated in advanced stages of gastric cancer patients who were given different platinum-based chemotherapy. PATIENTS AND METHODS: Forty-one patients with advanced gastric cancer were enrolled into the study from January 2000 to December 2009. ERCC1 expression was evaluated by immunohistochemistry (IHC). RESULTS: Thirteen of the 41 patients (31%) were shown to have ERCC1 positive lesions. Although the clinical benefit from platin based chemotherapy was the same for ERCC1 positive and negative patients, survival times were statistically significantly better in ERCC1 negative gastric cancer patients. CONCLUSION: We suggest that IHC studies for ERCC1 may be useful in prediction of the clinical outcome of advanced gastric cancer patients treated with platin-based chemotherapy.

Recovery of paraneoplastic hypercalcemia by sunitinib treatment for renal cell carcinoma: a case report and review of the literature.

Sunitinib is a novel oral multitargeted tyrosine kinase inhibitor. It has higher response rates and progression-free survival in patients with metastatic renal cell carcinoma (RCC) when compared with standard chemotherapy and interferon-alpha. We report a case of paraneoplastic hypercalcemia, resistant to conventional treatment but recovers by sunitinib treatment as the first case in the literature, in a 33-years-old man with metastatic RCC. At the sixth month of follow-up period, in this case, serum calcium level was still in normal ranges. Besides sunitinib is effective in symptom control, it is also helpful in management of paraneoplastic hypercalcemia, a life-threatening entity.

Triple-negative breast cancer: immunohistochemical correlation with basaloid markers and prognostic value of survivin.

OBJECTIVE: Among the subgroups of breast cancer, basaloid type has the shortest disease-free survival. Survivin is an apoptosis inhibitor and its prognostic and predictive value in breast cancer is under investigation. In this study, we examined the basaloid markers CK5/6, CK14, CK17, and EGFR in triplet-negative patients and evaluated the impact of survivin on survival. MATERIALS AND METHODS: Thirty patients with breast cancer in triplet-negative form admitted to Erciyes University Medical Oncology Department between 2001 and 2005 were included in the study. Median follow up and age were 45 months (range 5-76 months) and 47 years (range 23-76), respectively. Eighteen patients (60%) were premenopausal and 12 (40%) were postmenopausal. In total, 2, 12, and 14 patients had stage I, II, and III disease, respectively. When cytokeratines and survivin were analyzed independently, association between CK5/6 positivity and lymph node involvement was statistically significant (P = 0.014). In 70% of patients, CK5/6 or EGFR was found positive, and positive results were only had statistically significant correlation with age and menopausal status (P = 0.049 and 0.049, respectively). Ten patients (33.3%) totally and nine patients (42.8%) in the basaloid subgroup had positive staining for survivin. Survivin was not correlated with any of the clinical or histopathological features. While correlation between the number of involved lymph nodes, lymphovascular invasion, histopathological grade, and disease-free survival was statistically significant (P = 0.036, 0.002, and 0.035, respectively), this is not valid for CK5/6, EGFR, and survivin. CONCLUSION: CK5/6 or EGFR was accepted as determinants of basaloid breast cancer. The correlation between basaloid form and other histopathological markers did not reveal any significant difference with respect to prognostic and clinical parameters. We were unable to demonstrate the prognostic impact of survivin in patients with basaloid form or triplet-negative breast cancer.