Tyrosine kinase inhibitors in the treatment of metastatic renal cell cancer patients with early cytokine intolerance: TURCOS, a Turkish national, prospective observational study.

OBJECTIVE: Cytokines have been the mainstay of treatment in metastatic renal cell cancer (mRCC) for decades before the introduction of tyrosine kinase inhibitors (TKIs), which dramatically changed the therapeutic landscape in these patients. This observational study was designed to evaluate use of TKIs in the treatment of cytokine-intolerant mRCC patients. METHODS: A total of 151 cytokine-intolerant mRCC patients who were treated with TKIs (sunitinib, pazopanib and sorafenib) were enrolled in this prospective, non-interventional, multi-center observational study at 16 oncology centers across Turkey. Mean (SD) age was 61.3 (11.1) years and 74.8% were males. Data on duration of TKI treatment was the primary outcome measure. Additionally, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and safety data were recorded. RESULTS: Median duration of treatment was 8.2 months at a median follow up of 17.9 months. ORR and disease control rate were 12.5% and 70.8%, respectively. Median PFS and OS were 7.5 months (95%CI: 6.4-10.4) and 27.3 months (95%CI: 17.6-27.3) with no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. The most common adverse events excluding progression-which was the protocol requirement were diarrhea (13.6%), asthenia (13.6%) and hand-foot syndrome (12.6%). Dose modifications were required in 30.5% of the patients and 15% discontinued TKIs because of toxicity. CONCLUSIONS: Our findings confirm the efficacy and safety profile of TKIs in the first-line treatment of mRCC patients intolerant to cytokine treatment. There was no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS.Trial registration: TURCOS ClinicalTrials.gov Identifier: NCT01585974. Registered April 25, 2012.

A metastatic histiocytic sarcoma case with primary involvement of the tonsil.

Histiocytic sarcoma (HS) is an extremely rare and aggressive hematopoietic tumor. Although it can be seen at any anatomic location, the most common primary sites are skin as extranodal region, locations including the lymph nodes and gastrointestinal tract. To the best of our knowledge, in light of PubMed search, this is the first primary tonsillar HS case presented with disseminated metastases at the time of diagnosis. A 58-year-old male patient applied with swelling on the right side of the neck, difficulty in swallowing, and weight loss. Positron emission tomography computed tomography was performed and increased pathological 18F fluorodeoxy D glucose uptake was detected in the right palatine tonsil, bilateral cervical multiple lymph nodes, liver masses, intra abdominal lymph nodes, and nodular lesion in the left adrenal gland. Tonsillectomy was performed and the pathological result was reported as HS. The patient did not respond to any treatment and had died after 5 months from the date of diagnosis. In conclusion, HS is generally diagnosed at advanced stage, it has limited chemotherapy response and high mortality rates. To understand this rare disease's pathophysiological and clinical features, further investigations are needed.

Safety and efficacy of regorafenib in patients with treatment-refractory metastatic colorectal cancer in Turkey: the single-arm, open-label REGARD study.

OBJECTIVES: Regorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC. DESIGN: Open-label, single-arm, phase IIIb study conducted between July 2013 and April 2015. SETTING: 11 tertiary centres in Turkey. PARTICIPANTS: Eligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status ≤1. Patients were excluded if they had previously received regorafenib. Of 139 patients screened, 100 were treated and completed the study, and all 100 were analysed. Fifty-eight per cent were male. INTERVENTIONS: Patients received oral regorafenib, 160 mg once daily, for the first 3 weeks of each 4-week cycle until disease progression, death or unacceptable toxicity. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was safety, assessed by incidence of treatment-emergent adverse events (TEAEs). Progression-free survival (PFS) per investigator was the primary efficacy endpoint. There were no secondary endpoints. RESULTS: The median treatment duration was 2.5 months (range 0.1 to 20.6). Ninety-six per cent of patients had at least one TEAE and 77% had a grade ≥3 TEAE. The most common grade ≥3 regorafenib-related TEAEs were hypophosphataemia (11%), fatigue (8%), hyperbilirubinaemia (6%), hand-foot skin reaction (5%), hypertension (5%), anorexia (5%) and increased alanine aminotransferase (5%). TEAEs led to dose reduction in 30% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17% of patients. Median PFS was 3.1 months (95% CI 2.9 to 3.8). CONCLUSION: The regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC. TRIAL REGISTRATION NUMBER: NCT01853319, ClinicalTrials.gov.

Efficacy and toxicity of sorafenib in the treatment of advanced medullary thyroid carcinoma: A systematic review and meta-analysis.

INTRODUCTION: The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid carcinomas (MTCs). METHODS: We included studies reporting the treatment efficacy or drug toxicity of sorafenib as a single therapeutic agent in MTCs. Pooled incidence and its 95% confidence interval (CI) for complete response, partial response (PR), stable disease (SD), and sorafenib-related AEs were calculated using random-effect model. RESULTS: Eight trials with 101 metastatic MTCs were included for meta-analyses. The overall PR and SD were 21% (95% CI = 9-33) and 58% (95% CI = 41-75), respectively. Hand-foot syndrome, diarrhea, alopecia, mucositis, skin rash, fatigue, and hypertension were the most commonly observed AEs. CONCLUSION: Our results show that sorafenib treatment has a modest effect and might be a candidate treatment in patients with metastatic MTCs who have failed other therapeutic regimens.

Ewing's sarcoma of kidney in a 60-year-old patient with local recurrence: A rare occurrence.

Ewing's family of tumors is aggressive tumors and frequently arises from bone and soft tissue. They might also arise from nonosseous structures such as gastrointestinal tract, adrenal glands, or kidney. Primary renal Ewing's sarcoma (ES)/primitive neuroectodermal tumor is an extremely rare entity which has aggressive clinical course. These high-grade malignant tumors predominantly affect adolescents and young adults. Patients mostly present with nonspecific symptoms such as pain, hematuria, mass, and sensitivity. It is confused with renal cell cancer in imaging techniques. The definitive diagnosis is based on the histopathological examination. Surgical or radiotherapy treatment is used for local control and multiagent chemotherapy used for systemic treatment. Despite all treatment options, prognosis is poor. We aimed to describe the diagnosis and follow-up and treatment of renal ES case that was considered as renal cell carcinoma in imaging but diagnosed as ES via histopathology.

Lobular breast cancer metastasis to uterus during adjuvant tamoxifen treatment: A case report and review of the literature.

Tamoxifen plays a critical role in the treatment of hormone receptor-positive breast cancer. Despite these great benefits against breast cancer, tamoxifen increases the risk of endometrial pathologies such as endometrial hyperplasia, polyp, and neoplasms because of agonistic effect on endometrial tissues. Therefore, gynecologic follow-up should be carried out during tamoxifen treatment. Uterine tumors are frequently detected as the result of presentation with abnormal uterine bleeding. In addition, genital tract's metastases from distant primary tumors can present with abnormal uterine bleeding. Therefore, it is important to determine whether the uterine mass is metastatic or primary because different treatment modalities are used for them. In this context, breast carcinomas are the most frequent metastatic tumors, particularly invasive lobular carcinoma. Here, we report an invasive lobular carcinoma case that presented with abnormal uterine bleeding while receiving tamoxifen therapy and has metastasize in the uterus.

Hepatitis B and C rates are significantly increased in certain solid tumors: A large retrospective study.

Objective: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with significant morbidity and mortality among cancer patients who received cytotoxic chemotherapy. The aim of current study was to elucidate the prevalence of HBV and HCV among large population of solid cancers and lymphoma and to compare them with large number of control group. Patients and Methods: Between 2000 and 2014, 8322 cancer patients who were admitted to Oncology Departments were evaluated retrospectively and 3890 patients in whom hepatitis serology were available were included in this study. Their results were compared with control group that consisted of 96,000 subjects. Results: In control groups, hepatitis B surface antigen (HBsAg) positivity rate was 3.3% and anti-HCV positivity rate was 0.84%. In cancer patients, HBsAg positivity rate was 3.65% and anti-HCV positivity rate was 1.2%. Neither HBsAg positivity rate nor anti-HCV positivity rate was statistically significant between groups (P = 0.12 and P = 0.09, respectively). HBsAg positivity rates of head and neck cancer (5.88%; P = 0.02), rectum (5.6%; P = 0.025), and gastric and esophagus cancer (5.88%; P = 0.025) were significantly higher than control groups. Anti-HCV positivity rate (2.5%; P = 0.0016) was significantly higher in lung cancer when compared with control group. Conclusion: The current study elucidated the prevalence of HBV and HCV among large population of solid cancers and lymphoma and we showed that hepatitis B and C positivity rates are significantly increased in certain solid tumors. Our findings should also be clarified with large prospective studies.

Effectiveness and Safety of LMWH Treatment in Patients With Cancer Diagnosed With Non-High-Risk Venous Thromboembolism: Turkish Observational Study (TREBECA).

We compared the efficacy and safety of low-molecular-weight heparins (LMWHs) in patients with cancer who are at low risk of venous thromboembolism (VTE). Patients were treated by medical oncologists in Turkey at 15 sites, where they were enrolled and followed up for a period of 12 months. Due to the study design, there was no specific treatment protocol for LMWH. Primary end points were efficacy and the time to change in VTE status. Of the included 250 patients, 239 (95.6%), 176 (70.4%), 130 (52.0%), and 91 (36.4%) completed their day 15, month 3, month 6, and month 12 visits, respectively. Number of patients treated with enoxaparin, bemiparin, and tinzaparin were 133, 112, and 5, respectively. Anticoagulant therapy provoked thrombus resolution in 1.2% and 12.7% of patients using enoxaparin and bemiparin, respectively ( P = .004). Thrombus resolution was observed in 81 more patients at month 3 visit. This ratio was 35 (40.2%) of 87 and 46 (54.1%) of 85 patients administered enoxaparin and bemiparin at the third visit, respectively ( P = .038). Thrombus resolution was observed in 21 more patients during month 6 visit. This ratio was 5 (7.7%) of 65 and 15 (23.4%) of 64 patients administered enoxaparin and bemiparin at the fourth visit, respectively ( P = .022). The LMWH was discontinued in only 2 patients due to gastrointestinal bleeding. This pioneering study shows bemiparin is more effective than enoxaparin in thrombosis resolution and has a similar tolerability profile.

A case of membranous glomerulopathy associated with lung cancer and review of the literature.

Membraneous nephropathy (MN) is the most commonly occurring nephrotic syndrome in adults as well as the most common paraneoplastic nephropathy associated with solid tumors, and it is mostly associated with gastrointestinal system and lung carcinomas. Accurate diagnosis is important as the treatment of paraneoplastic glomerulonephritis is very varied from that of idiopathic ones. In the current report, a case of a patient that was referred with proteinuria and edema and was diagnosed with lung cancer, and responded markedly to treatment of malignancy, with improvement of MN, is presented. Active cancer is present in all patients with paraneoplastic MN. In numerous patients, the paraneoplastic MN and cancer diagnoses are made within one year of each other. The treatment of paraneoplastic syndromes is usually associated with the treatment of primary malignancy. There are conflicting data on which treatment modality is more suitable. In conclusion, further studies are required in order to determine the actual incidence of cancer in patients with nephropathy, explain the physiopathological association between cancer and nephropathy and to determine the most suitable treatment approaches.

Renal cell cancer: overview of the current therapeutic landscape.

INTRODUCTION: The last decade has witnessed dramatic improvements in the diagnosis, classification and treatment of renal cell cancer (RCC). Besides improvements in surgical techniques in early stages, introduction of novel targeted agents has resulted in improved outcomes in advanced RCC for which no effective treatment existed until recently. AREAS COVERED: This article reviews epidemiology, pathology and pathogenesis, diagnosis, clinical staging, prognostic factors and treatment modalities of early stage and advanced RCC. Expert commentary: Although treatment options are expanding rapidly, practicing physicians face considerable challenges in the decision-making process. Therapeutic agents may have unique side effects and unexpected drug interactions. RCC represents one of the major success stories of clinical oncology in recent years and the progress appears to be far from having reached a plateau. We aim to present a comprehensive in-depth review of RCC in an attempt to provide evidence-based recommendations and future perspectives for practicing oncologists.

Multicenter experience of adult medulloblastoma: A study of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Medulloblastoma (MB) is rarely seen in adults. For adjuvant therapy in adults the same therapy protocols used in pediatric cases are used. The present study retrospectively evaluated the data of MB patients who were treated in different Oncology Centers in Turkey. METHODS: The data of 60 adult patients with MB from 8 Oncology Centers diagnosed between 2005 and 2012 were retrospectively analyzed. RESULTS: The median patient age was 28.8 years (range 16-54). The administered chemotherapy included procarbazine+lomustin+vincristine (group A, N=31) and cyclophosphamide/ifosfamide+vincristine+cisplatin (group B, N=13). Median chemotherapy courses were 4 (range 1-8). Median progression free survival (PFS) was 76 months and median overall survival (OS) has not been reached in both groups. In young female patients and in those who received adjuvant chemotherapy, median PFS and OS were longer but without statistical significance. Mean PFS and OS were 65.9 months and 101.2 months in group A and 113.6 months and 141.6 months in group B, respectively. CONCLUSION: Improved survival results were obtained in women, in patients aged below 25 years, in those who underwent gross total excision (GTE) and in those who received adjuvant therapy with cyclophosphamide/ifosphamide.

Crizotinib-induced toxicity in an experimental rat model.

AIM: The aim of the present study was to evaluate the effect of crizotinib on visceral organs in an experimental rat model. METHODS: Eighteen Wistar albino rats were divided into three groups: experimental toxicity was induced with crizotinib (10 mg/kg) administered for 28 days (Group 1), 42 days (Group 2) orally by gavage. Control group received only distilled water. Rats in Group 1 and Group 2 were sacrificed after the collection of blood and tissue samples on the 28th and 42nd days, respectively. RESULTS: Subjects in Group 1 and Group 2 had abnormal histology mainly in lung and liver. There were intraalveolar hemorrhage in lungs; mild portal inflammation, perivenular focal and confluent necrosis in liver; inflammatory reaction in renal pelvis and periureteral areas, and focal pancreatitis in pancreas. CONCLUSION: This study is the first to evaluate the histopathological features of toxicity of crizotinib in a rat model.

Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab.

PURPOSE: The aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab. METHODS: Medical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively. RESULTS: Median follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER- and PR-) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33-8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33-8.71) were significant risk factors for development of brain metastasis as the first site of recurrence. CONCLUSIONS: In patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER- and PR-) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.

Liver metastases from adenocarcinomas of unknown primary site: management and prognosis in 68 consecutive patients.

BACKGROUND: In this retrospective study, we aimed to evaluate the clinicopathological characteristics of the patients presenting with liver metastases from unknown primary site besides survival rates, treatment outcomes, and prognostic factors. METHODS: In all, 68 patients followed-up at our center with adenocarcinoma of unknown primary (ACUP) metastatic to the liver between 2005 and 2013 were enrolled. All of the liver metastases were proven by liver biopsy and all yielded diagnosis of adenocarcinoma. RESULTS: Median age was 61 years (29-90) and most of the patients were male (male/female: 43/25). The liver was the only metastatic site in 2 (3%) patients whilst 66 patients (97%) had extrahepatic metastases. The most common extrahepatic metastatic sites were lymph nodes (89.7%), lungs (32.4%), bones (25%), peritoneum (11.8%), brain (4.4%), and adrenal glands (2.9%). Of all 68 patients, 39 (57.4%) were treated with chemotherapy. Median overall survival (OS) was significantly higher in ACUP patients treated with chemotherapy [12.5 months (95% CI 8.3-16.7) vs. 4 months (95% CI 1.2-6.8), (p = 0.026), respectively]. In multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status (p = 0.009), chemotherapy (p = 0.024), serum albumin (p = 0.012), and serum CA 19-9 level (p = 0.026) at initial diagnosis were identified as independent prognostic factors influencing survival for the patients with liver metastases from ACUP. CONCLUSION: Patients with liver metastases from ACUP have poor prognosis and chemotherapy improves survival. Decreased serum albumin level, increased CA 19-9 level and poor performance status are independent poor prognostic factors.

Factors Influencing Chemotherapy Goal Perception in Newly Diagnosed Cancer Patients.

Cancer patients who start receiving chemotherapy have difficulty in understanding the state of their disease, the prognosis, and the purpose of treatment. We used a survey to evaluate the extent of perception of chemotherapy goal among cancer patients. Two hundred sixteen cancer patients who received chemotherapy for the first time participated in the study. The presence of depression and anxiety was assessed using the "Hospital Anxiety and Depression Scale" (HAD). The consistency between the patients' perception of the chemotherapy goal and the physician's perception was described as "right," and the inconsistency was described as "wrong." Among the patients who participated in the survey, 53.2 % (n = 115) were receiving adjuvant treatment and 46.8 % (n = 101) were receiving palliative treatment for metastatic disease. The rate of right and wrong perception of the chemotherapy goal was 51.9 % (n = 108) and 32.2 % (n = 67), respectively, and the rate of confused patients was 18.9 % (n = 41). The level of education was shown to be the only parameter involved in accurate perception of the treatment purpose (hazard ratio (HR) = 0.444, p = 0.025, 95 % confidence interval (CI) 0.219-0.903). In this study, there was a 51.9 % consistency between the physician's perception and that of the patient regarding the purpose of treatment. We demonstrated that the level of education was the unique factor in accurate perception of chemotherapy goal among cancer patients.

Small cell neuroendocrine carcinoma of the posterior tongue.

In the head and neck mucosa, neuroendocrine carcinomas of the oral cavity is rare. Herein, we present the first report of a small cell neuroendocrine carcinoma in a 54-year-old man on the right lateral posterior tongue. It is important to remember that although neuroendocrine small cell carcinomas (SCCs) are most commonly seen in the lung, they rarely may arise in the extrapulmonary sites, including salivary glands, as well. As there is not any standard therapeutic regimen already existing, it is important to be aware of and to know how to deal with such rare cases.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.