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1.  Intraperitoneal Follicular Dendritic Cell Sarcoma: Role of Chemotherapy and Bone Marrow Allotransplantation in Locally Advanced Disease? 
We describe a case of a 44 year-old woman diagnosed with follicular dendritic cell sarcoma (FDCS). FDCS is a very rare disease affecting the dendritic antigen presenting cells and is often misdiagnosed. Surgery is considered the best treatment modality, followed by chemotherapy. In our case, surgical excision was not possible, therefore the patient received two lines of chemotherapy followed by bone marrow allotransplantation, then a third line of chemotherapy with a complete metabolic response seen on PET/computed tomography (CT) follow-up 29 months later. A review of the literature has been performed.
PMCID: PMC4324466
intraperitoneal; follicular dendritic cell sarcoma (FDCS); chemotherapy; bone marrow allotransplantation
2.  Cisplatin, Cetuximab, and Radiation in Locally Advanced Head and Neck Squamous Cell Cancer: A Retrospective Review 
Efficacy of cisplatin versus cetuximab with radiation in locally advanced head and neck cancer (LAHNC) was evaluated. A total of 96 patients with newly diagnosed LAHNC treated at our institution between 2006 and 2011 with concurrent radiation and cisplatin (group A, n = 45), cetuximab (group B, n = 24), or started with cisplatin but switched to cetuximab because of toxicity (group C, n = 27) were reviewed. Chi-square test, analysis of variance, and log-rank test were used for analysis. The three groups had similar baseline characteristics, except for median age, T stage, albumin levels, hemoglobin levels, performance status, and comorbidities. A complete response (CR) was seen in 77%, 17%, and 67% of patients (P < 0.001), respectively. There was no significant difference in median overall survival (OS) between groups A and C. The median OS for groups A and C was not reached (>65 months), even though it was significantly longer than median OS for group B (11.6 months; P ≤ 0.001). The 2-year OS in groups A and C is significantly higher than that in group B (70% for groups A and C, 22% for group B). There is no significant difference in progression-free survival (PFS) between groups A and C. The median PFS for these groups was not reached (>62 months), and is significantly longer than that for group B (4.3 months; P ≤ 0.001). The 2-year PFS of group A (67%) and group C (76%) was significantly longer than that of group B (20%). Cisplatin with radiation appears to be more efficacious even in suboptimal dosing than cetuximab with radiation in LAHNC but the two groups were not well matched.
PMCID: PMC4283547  PMID: 25628515
head and neck cancer; cetuximab; cisplatin; radiation therapy; overall survival
3.  Clinicians’ Expectations for Gene-Driven Cancer Therapy 
A new era of medicine is rapidly approaching, which will change not only pathological diagnosis but also medical decision-making. This paper raises the question of how well prepared doctors are to address the new issues that will soon confront them. The human genome has been completely sequenced and general understanding about cancer biology has increased enormously with understanding that unregulated gene function and complicated changes in signal pathways are related to uncontrolled cell growth. Thus, gene-driven therapy involving alterations to genes are recognized to present new therapy options. This advance will necessitate major changes to the decision-making aspect of physicians. This article focuses on defining the pertinent changes and addressing what they mean for practicing physicians.
PMCID: PMC4271717  PMID: 25574148
gene alteration; medical decision; individualized medicine
4.  Changes in Protein Level in the Cerebrospinal Fluid of a Patient with Cerebral Radiation Necrosis Treated with Bevacizumab 
A 32-year-old woman underwent surgeries and radiation therapy for astrocytoma. She developed symptomatic radiation necrosis in the lesion, which caused hydrocephalus. She initially underwent ventricular drainage, because the protein level in the cerebrospinal fluid (CSF) was 787 mg/dL, which was too high for shunt surgery. Because she also had breast cancer, which was pathologically diagnosed as an invasive ductal carcinoma, standard bevacizumab therapy in combination with paclitaxel every 2 weeks was selected. Interestingly, after 2 days, the agents had dramatically reduced the CSF protein level. However, it returned to approximately the initial level within 2 weeks. After two courses of this regimen, a ventriculoperitoneal shunt was placed. After 10 courses of this regimen, the CSF protein level decreased to 338 mg/dL, which is less than half of the initial level. Long-term administration of bevacizumab might decrease leakage of protein from the vessels around the ventriculus.
PMCID: PMC4263439  PMID: 25574147
bevacizumab; radiation necrosis; cerebrospinal fluid protein; glioma; radiosurgery; tomotherapy
5.  Micro-cost Analysis of ALK Rearrangement Testing by FISH to Determine Eligibility for Crizotinib Therapy in NSCLC: Implications for Cost Effectiveness of Testing and Treatment 
Break-apart fluorescence in situ hybridization (FISH) is the gold standard test for anaplastic lymphoma kinase (ALK) gene rearrangement. However, this methodology often is assumed to be expensive and potentially cost-prohibitive given the low prevalence of ALK-positive non-small cell lung cancer (NSCLC) cases. To more accurately estimate the cost of ALK testing by FISH, we developed a micro-cost model that accounts for all cost elements of the assay, including laboratory reagents, supplies, capital equipment, technical and pathologist labor, and the acquisition cost of the commercial test and associated reagent kits and controls. By applying a set of real-world base-case parameter values, we determined that the cost of a single ALK break-apart FISH test result is $278.01. Sensitivity analysis on the parameters of batch size, testing efficiency, and the cost of the commercial diagnostic testing products revealed that the cost per result is highly sensitive to batch size, but much less so to efficiency or product cost. This implies that ALK testing by FISH will be most cost effective when performed in high-volume centers. Our results indicate that testing cost may not be the primary determinant of crizotinib (Xalkori®) treatment cost effectiveness, and suggest that testing cost is an insufficient reason to limit the use of FISH testing for ALK rearrangement.
PMCID: PMC4260793  PMID: 25520569
micro-cost; ALK rearrangement; FISH; cost effectiveness; crizotinib; companion diagnostic
6.  The Use of Pharmacogenomics for Selection of Therapy in Non-Small-Cell Lung Cancer 
Performance status (PS) is the only known clinical predictor of outcome in patients with advanced non-small-cell lung cancer (NSCLC), although pharmacogenomic markers may also correlate with outcome. The aim of our study was to correlate clinical and pharmacogenomic measures with overall survival.
This was an IRB approved, retrospective study in which the medical records of 50 patients with advanced NSCLC from 1998–2008 were reviewed, and gender, race, PS, and chemotherapy regimens were documented. Stromal expression of pharmacogenomic markers (VEGFR, ERCC1, 14-3-3σ, pAKT, and PTEN) was measured. Clinical factors and pharmacogenomics markers were compared to overall survival using a Cox proportional hazards model.
Forty patients received platinum-based therapy. Median age was 65 years. Improved PS, female gender, and gemcitabine therapy were significantly associated with longer overall survival (P = 0.004, P = 0.04, and P = 0.003, respectively). Age was not associated with survival. Caucasians had better overall survival in comparison to African Americans with median survival of 14.8 months versus 10.4 months (P = 0.1). Patients treated with platinum-based therapy had better survival of 15 months versus 8 months for non-platinum based therapy (P = 0.01). There was no significant association between any of the pharmacogenomics markers and overall survival other than in patients treated with platinum, in whom ERCC1 negativity was strongly associated with longer survival (P = 0.007).
ERCC1 negativity with platinum therapy, gemcitabine therapy, good PS, and female gender all correlated with improved overall survival in patients with advanced NSCLC.
PMCID: PMC4259862  PMID: 25520568
pharmacogenomics; selection of therapy; non-small-cell lung cancer
7.  Cancer-Associated Thrombosis: An Overview 
Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Emerging data have enhanced our understanding of cancer-associated thrombosis, a major cause of morbidity and mortality in patients with cancer. In addition to VTE, arterial occlusion with stroke and anginal symptoms is relatively common among cancer patients, and is possibly related to genetic predisposition. Several risk factors for developing venous thrombosis usually coexist in cancer patients including surgery, hospital admissions and immobilization, the presence of an indwelling central catheter, chemotherapy, use of erythropoiesis-stimulating agents (ESAs) and new molecular-targeted therapies such as antiangiogenic agents. Effective prophylaxis and treatment of VTE reduced morbidity and mortality, and improved quality of life. Low-molecular-weight heparin (LMWH) is preferred as an effective and safe means for prophylaxis and treatment of VTE. It has largely replaced unfractionated heparin (UFH) and vitamin K antagonists (VKAs). Recently, the development of novel oral anticoagulants (NOACs) that directly inhibit factor Xa or thrombin is a milestone achievement in the prevention and treatment of VTE. This review will focus on the epidemiology and pathophysiology of cancer-associated thrombosis, risk factors, and new predictive biomarkers for VTE as well as discuss novel prevention and management regimens of VTE in cancer according to published guidelines.
PMCID: PMC4259501  PMID: 25520567
cancer; thrombosis; management; low-molecular-weight heparin
8.  Phase II Clinical Trial of Gefitinib for the Treatment of Chemonaïve Patients with Advanced Non-small Cell Lung Cancer with Poor Performance Status 
Patients with advanced non-small cell lung cancer (NSCLC) have no curative treatment options; therefore, improving their quality of life (QOL) is an important goal. Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, is a safe oral agent that may be of benefit to a specific population of NSCLC.
A Phase II clinical trial included chemonaïve patients with advanced NSCLC and poor performance status (PS). Response rate, progression-free survival, overall survival, QOL using the Functional Assessment of Cancer Therapy – Lung (FACT-L) questionnaire, and Trial Outcome Index (TOI) were evaluated.
Twelve out of 19 enrolled patients were evaluable. The median age for the evaluable patients was 68.8 years (59.7–74.6). Out of all the patients, 7 (58.3%) had adenocarcinoma and 5 (41.7%) had squamous cell carcinoma. The median duration of treatment was 62.5 days (26.5–115.0) in the evaluable patients. Grade 3/4 toxicities included fatigue, rash, diarrhea, and nausea. One patient had partial response, eight patients had stable disease (SD), and three patients progressed. The median overall survival for the evaluable population was 4.9 months (2.3–16). The median progression-free survival was 3.7 months (1.9–6.6). TOI was marginally associated with the overall survival, with a hazard ratio of 0.92 (95% confidence interval: 0.84, 1.0) (P = 0.061). FACT-L score and the TOI were highly correlated (r = 0.96, P < 0.0001). TOI scores were higher in African Americans compared to Caucasians and increased with age.
Our results suggest that gefitinib use in patients with NSCLC and poor PS may improve the QOL of older patients and African American patients.
PMCID: PMC4245085  PMID: 25520566
advanced non-small cell lung cancer; poor performance status; gefitinib; quality of life
9.  Human Papilloma Virus and Squamous Cell Carcinoma of the Anus 
The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer. This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus.
PMCID: PMC4179600  PMID: 25288893
anal cancer; squamous cell carcinoma; basaloid carcinoma; surgery
10.  Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information 
The St. Gallen International Expert Consensus of 2011 proposes a new classification system for breast cancer based on its division into five subgroups. The criteria to identify these subtypes were recently refined at the 2013 Conference. In this respect, the authors of this paper have conducted a retrospective analysis of breast cancer subtypes, related to Ki-67 and involvement of the axillary lymph nodes (ALNs). The analysis was performed only in the cases of invasive breast cancer in the pT2 stages. The research and results of the paper have shown that investigating the value of these parameters could be of great benefit in future treatment strategies of invasive breast cancer.
A retrospective analysis of breast cancer subtypes, tumor nodal metastatic staging, and histopathological grading of 108 cases has been performed according to the methods recommended and provided by the St. Gallen International Expert Consensus Report, 2011. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 of 108 tumor samples were all investigated by immunohistochemistry according to the methods used to classify breast cancer subtypes as proposed in the St. Gallen Consensus Report, 2011. Invasive breast cancers (n = 108) were immunohistochemically classified as follows: 28 (25.92%) as Luminal A, 51 (47.22%) as Luminal B (HER2 negative), 21 (19.44%) as Luminal B-like (HER2 negative), 2 (1.85%) as HER2 positive, and 6 (5.55%) as being a triple-negative subtype.
The conclusion was made that when Ki-67 was found to be higher, patients also showed a higher involvement in their ALNs. The chi-square test shows the difference to be significant (chi-square = 4.757; P = 0.029). Luminal B subtypes had the highest percentage (54.9%) of involvement of lymph nodes when compared to the other four subtypes. The Luminal B subtype had a higher percentage (51.4%) of involvement of lymph nodes than did Luminal A (10.7%). The chi-square test also shows the difference to be significant (P < 0.05).
A combination of the Ki-67 index, HER negative tumors, PR negativity, and a low value that can be used to segregate ER positive pT2 tumors into prognostically significantly different clinical outcomes may be utilized clinically to guide patient management in accordance with these tumor characteristics.
PMCID: PMC4167319  PMID: 25249766
breast cancer; Luminal A; Luminal B; Ki-67; positive lymph node status; prognostic information
11.  Tandem Autologous Stem Cell Transplantation for Multiple Myeloma Patients Based on Response to Their First Transplant—A Prospective Phase II Study 
In this prospective phase II clinical trial, multiple myeloma (MM) patients were randomized to receive a second (tandem) autologous stem cell transplantation (ASCT) based on whether they achieved a partial response or worse (≤PR) following initial ASCT (ASCT1). Patients who achieved a very good partial response or better (≥VGPR) had salvage ASCT at relapse. Seventy-five patients received conditioning therapy and ASCT1. A total of 44 patients (59%) achieved ≥VGPR, whereas 31 patients entered ≤PR and were offered tandem ASCT. In all, 20 patients agreed to tandem ASCT. Demographic and clinical characteristics were similar between the two cohorts except for median lactate dehydrogenase (LDH) (P = 0.0141) and percentage of marrow plasma cells before ASCT1 (P = 0.0047), both lower in the ≥VGPR group. Intent to treat analysis showed that patients who achieved ≥VGPR to ASCT1 had a trend toward improved progression-free survival (PFS) (37 vs. 26 months, P = 0.078) and superior overall survival (OS) (not reached vs. 50 months, P = 0.0073). Patients with ≤PR who declined tandem transplantation had shortened PFS (20 vs. 28 months, P = 0.05) but similar OS (53 vs. 57.5 months, P = 0.29) compared to those who received it. Thus, a favorable clinical response to ASCT1 identifies a low-risk group with superior long-term prognosis despite similar PFS.
PMCID: PMC4159376  PMID: 25232286
multiple myeloma; autologous stem cell transplantation; tandem; survival
12.  Update on the Use of l-Asparaginase in Infants and Adolescent Patients with Acute Lymphoblastic Leukemia 
Great improvements have been made in acute lymphoblastic leukemia (ALL) treatment in the past decades, especially due to the use of l-asparaginase (l-ASP). Despite the significant success rate, several side effects mainly caused by toxicity, asparaginase silent inactivation, and cellular resistance, encourage an open debate regarding the optimal dosage and formulation of l-ASP. Alternative sources of asparaginases have been constantly investigated in order to overcome hypersensitivity clinical toxicity. Additionally, genomic modulation as gene expression profiling, genetic polymorphisms, and epigenetic changes is also being investigated concerning their role in cellular resistance to l-ASP. Understanding the mechanisms that mediate the resistance to l-ASP treatment may bring new insights into ALL pathobiology and contribute to the development of more effective treatment strategies. In summary, this review presents an overview on l-ASP data and focuses on cellular mechanisms underlying resistance and alternative therapies for the use of asparaginase in childhood ALL treatment.
PMCID: PMC4149393  PMID: 25210485
asparaginase; acute lymphoblastic leukemia; molecular resistance mechanisms; therapy updates
13.  Case Report About Fatal or Near-Fatal Hypersensitivity Reactions to Cetuximab: Anticetuximab IgE as a Valuable Screening Test 
Hypersensitivity reactions are a classic side effect of cetuximab. We report the cases of three patients who developed life-threatening hypersensitivity to cetuximab, which could have been predicted by assessing the concentration of serum anticetuximab immunoglobulin (Ig)E. The anticetuximab IgE concentration could be an interesting test to predict which patients are at risk of experiencing severe hypersensitivity reactions to cetuximab.
PMCID: PMC4116358  PMID: 25089092
hypersensitivity; anaphylaxis; cetuximab; antidrug IgE; neoplasms
14.  Advanced Extramammary Paget’s Disease of the Groin, Penis, and Scrotum 
Extramammary Paget’s disease (EMPD) is a rare intraepithelial malignancy arising in areas rich in apocrine glands, such as the perineum, vulva, axilla, scrotum, and penis. We describe the case of a man in his 50s who initially presented with a small eczematous lesion on his right groin, treated with topical ointments for eczema, until excisional biopsy of lesion unequivocally revealed invasive EMPD. Despite aggressive surgical interventions, his disease progressed to involve the scrotum and penis. Deemed unresectable, the patient was treated with systemic chemotherapy with minimal response. The rarity of EMPD, especially of the penis and scrotum, warrants an educated eye and heightened index of suspicion when dealing with eczematous lesions in the groin in any person. Early biopsy and histological examination is crucial for early surgical intervention of the lesions. There are no guidelines available to treat locally advanced unresectable disease. In addition, further studies are needed to identify genetic defects underlying the pathogenesis of this rare disease, to help improve treatment strategies and decrease morbidity.
PMCID: PMC4116380  PMID: 25089091
Extramammary Paget’s disease (EMPD); eczematous lesion; intraepithelial malignancy
15.  The Prognostic Role of the Neutrophil-to-Lymphocyte Ratio in Oropharyngeal Carcinoma Treated with Chemoradiotherapy 
The aim of the study is to investigate the prognostic role of pre-treatment of markers of the systemic inflammatory response (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin) in patients with oropharyngeal carcinoma treated with chemoradiotherapy.
A total of 251 patients with oropharyngeal squamous cell cancer treated with chemoradiotherapy between 2004 and 2010 were retrospectively identified. NLR, PLR, and albumin were recorded from baseline blood parameters. NLR threshold of >5 and PLR thresholds of ≤150, >150 and ≤300, and >300 were used for analysis.
Median follow-up was 46 months (range 9–98). The 3 year overall survival, local control, regional control, and distant control were 70%, 85%, 87%, and 87%, respectively. On multivariate analysis, locoregional control was associated with T stage (HR 3.3 (95% CI 1.5–6.9), P = 0.002) and NLR (HR 2.1 (95% CI 1.1–3.9), P = 0.023). Overall survival was associated with T stage (HR 2.47 (95% CI 1.45–4.2), P = 0.001) and grade (HR 0.61 (95% CI 0.38–0.99), P = 0.048). PLR and albumin were not significantly associated with disease outcomes or survival.
The NLR is an independent prognostic factor for locoregional control in oropharyngeal cancer treated with chemoradiotherapy.
PMCID: PMC4085107  PMID: 25057245
oropharynx cancer; squamous cell cancer; chemotherapy; radiotherapy; neutrophil-to-lymphocyte ratio
16.  Vismodegib: the Proof of Concept in Basal Cell Carcinoma 
Although basal cell carcinoma (BCC) is the most common cancer worldwide, its metastatic dissemination is exceptional. Before 2012, we had a few treatment options available for metastatic or locally advanced cases. Management of these patients was complicated due to the lack of scientific data, the deterioration of a patient’s general status, the patient’s advanced age, and the presence of multiple comorbidities. The hedgehog signaling pathway is dysregulated in BCC. The exploration of this signaling pathway yielded to a major milestone in the treatment of advanced BCC. Vismodegib (GDC-0449), an oral small-molecule agent that targets the Hedgehog signaling pathway, demonstrates high levels of activity in clinical trials. It was approved in January 2012 for the treatment of locally advanced or metastatic BCC. Vismodegib confirms, once again, the interest in exploring the signal transduction pathways in cancers.
PMCID: PMC4051803  PMID: 24932107
basal cell carcinoma; hedgehog; vismodegib; cetuximab
17.  Emerging Trends in Hepatocellular Carcinoma: Focus on Diagnosis and Therapeutics 
Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and one of the deadliest. Patients with chronic liver disease are at the highest risk for developing this tumor. This link provides an opportunity for developing preventive strategies and surveillance that aims at early detection of this tumor and possibly improving outcomes. In this review, we will discuss the latest developments in surveillance strategies, diagnosis, and treatment of this tumor. HCC is the sixth most common cancer in the world, with 782,000 new cases occurring in 2012 worldwide. In 2012, there were 746,000 deaths from liver cancer.1 HCC is the third most fatal cancer in the world.2 The distribution of HCC, which varies geographically, is related to the prevalence of hepatotropic virus. The burden of the disease is the highest in Eastern Asia, sub-Saharan Africa, and Melanesia where hepatitis B (HBV) infection is endemic. Meanwhile, in Japan, United States, and Europe, hepatitis C (HCV) infection is prevalent, and subsequently, is the major risk factor for acquiring HCC in these regions.1,3 It is estimated that the incidence of HCC in Europe and United States will peak at 2020—there will be 78,000 new HCC cases in Europe and 27,000 in the United States—and decline thereafter.1 Indeed, in Japan, the incidence of HCC had already plateaued and started to slowly fall.4 Cirrhosis is the most important risk factor for HCC regardless of etiology and may be caused by chronic viral hepatitis (mainly HBV and HCV), alcoholic liver disease, autoimmune disease, Stage 4 primary biliary cirrhosis, and metabolic diseases such as hereditary hemochromatosis, alpha-1 antitrypsin deficiency, and non-alcoholic fatty liver disease. In the Western hemisphere, HCC occurs in a background of cirrhosis in 90% of the cases.5 Before concentrating on diagnosis and therapeutics, it is important to discuss surveillance for this tumor.
PMCID: PMC4039215  PMID: 24899827
hepatocellular carcinoma (HCC); alpha-fetoprotein (AFP); ultrasound; dynamic imaging; liver transplantation; radiofrequency ablation (RFA); trans-arterial chemoembolization (TACE); Yttrium-90 (Y-90) radioembolization; sorafenib; molecular targets
18.  Oncology Nursing Support for Safe and Effective Use of Eribulin in Metastatic Breast Cancer 
Nurse practitioners play important roles in breast cancer prevention, early detection, therapeutic efficacy, and surveillance. Assessment of a patient’s health status is part of the nine nurse practitioner core competencies updated in 2012 by the National Organization of Nurse Practitioner Faculties. Although adverse events are common in treatment for metastatic breast cancer (MBC), proactive management strategies can limit the number and/or severity of adverse events. Additionally, knowledge of common metastatic sites and clinical signs/symptoms of recurrence provides one of the first-line strategies for successful treatment. We review five case studies of women with MBC who were managed successfully with eribulin mesylate in late lines of therapy after at least two chemotherapeutic regimens for advanced breast cancer that included both an anthracycline and a taxane in either the adjuvant or metastatic setting.
PMCID: PMC4022698  PMID: 24855406
eribulin; metastatic breast cancer; distant breast cancer metastases; eribulin-related AE management
19.  What is the Best Treatment for a Cancer Patient with Thrombosis? 
The relationship between venous thromboembolism and cancer has been known for many years, and there is solid scientific evidence addressing the adequate treatment of this condition in oncology patients. However, established prescribing habits, individual patient challenges, and uncertainty concerning treatment justifies poor adherence to published guidelines. This paper reviews venous thromboembolism treatment while focusing on vitamin K antagonists, low-molecular-weight heparins, and novel oral anticoagulants, namely in terms of their efficacy and limitations.
PMCID: PMC4011719  PMID: 24855404
venous thromboembolism; cancer; thrombosis; vitamin K antagonists; low-molecular-weight heparin; oral anticoagulants
20.  Influenza Vaccination in Cancer Patients Undergoing Systemic Therapy 
Cancer patients often experience preventable infections, including influenza A and B. These infections can be a cause of significant morbidity and mortality. The increased risk of infection may be because of either cancer itself or treatment-induced immunosuppression.1 Influenza immunization has been shown to decrease the risk of influenza infection in patients with intact immunity.2 In cancer patients, active immunization has been shown to confer protective immunity against several infections at similar rates to healthy individuals, which has translated into decreased duration and severity of infection and potentially improved morbidity and mortality.3
To assess the efficacy of influenza vaccination in stimulating immunological response in patients with cancer during chemotherapy compared to control groups.
To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or stimulating immunological response in children with cancer treated with chemotherapy, compared to placebo, no intervention, or different dosage schedules.
To determine the adverse effects associated with influenza vaccination in patients with cancer.
We searched MEDLINE/PubMed database for articles published from 1964 to 2013 using the search terms “cancer,” “adult,” “influenza vaccination,” and “chemotherapy.”
We included studies based on systematic sampling with defined clinical criteria irrespective of the vaccination status of cancer patients. Studies measure the serological response or clinical response to compare between the study group and the control group. Studies assessed the inactivated influenza vaccines and live attenuated influenza vaccine (LAIV) protective serological reaction and the clinical outcomes after vaccination.
Two independent authors assessed the methodological quality of included studies and extracted data.
We included 16 studies (total number of participants = 1,076). None of the included studies reported clinical outcomes. All included studies reported on influenza immunity and adverse reaction on vaccination. We included 6 solid tumor studies and 10 hematological studies. In 12 studies, the serological response to influenza vaccine was compared in patients receiving chemotherapy (n = 425) versus those not receiving chemotherapy (n = 376). In three studies, the serological responses to influenza vaccination in patients receiving chemotherapy are compared to that in healthy adult. Measures used to assess the serological responses included a four-fold rise increase in antibody titer development of hemagglutination inhibition (HI) titer >40, and pre- and post-vaccination geometric mean titers (GMTs). Immune responses in patients receiving chemotherapy were consistently weaker (four-fold rise of 17–52%) than in those who had completed chemotherapy (50–83%) and healthy patients (67–100%). Concerning adverse effects, oncology patients received influenza vaccine, and the side effects described were mild local reactions and low-grade fever. No life-threatening or persistent adverse effects were reported.
Patients with solid and some of hematological tumors are able to mount a serological response to influenza vaccine, but it remains unclear how much this response protects them from influenza infection or its complications. Meanwhile, influenza vaccine appears to be safe in these patients. While waiting results of randomized controlled trials to give us more details about the clinical benefits of the influenza vaccination, the clinicians should consider the currently proved benefits of influenza vaccination on management of the cancer patients undergoing systematic chemotherapy such as decrease in the duration and severity of the of the disease, and significant decrease in influenza-associated morbidity and mortality in these high-risk patients.3
PMCID: PMC4011725  PMID: 24855405
influenza vaccination; cancer patients; chemotherapy
21.  The Importance of Multidisciplinary Approach in Early Detection of BAP1 Tumor Predisposition Syndrome: Clinical Management and Risk Assessment 
Germline BAP1 (BRCA1-associated protein-1) mutations are involved into a novel specific cancer syndrome and strictly associated with a high cancer susceptibility. Recent data suggest that BAP1 has activity toward target substrates explaining why loss of BAP1 causes a pro-tumorigenic deregulation of gene expression. The recently published data reviewed raise the hypothesis that BAP1 regulates a common subset of substrates, which in turn causes a pro-tumorigenic deregulation of gene expression, and alternatively suggest the role of BAP1 as tumorigenesis suppressor/promoter also by independent mechanisms. The clinical phenotype of BAP1 alterations includes MBAITs (melanocytic BAP1-mutated atypical intradermal tumors), uveal melanoma (UM), cutaneous melanoma (CM), renal cell carcinoma (RCC), mesothelioma (MM), and possibly several other tumors. In clinical practice, early diagnosis is crucial for curative resection of all these tumor types. The uniformed and unambiguous definition of MBAITs as clinical/pathological predictive markers could provide physicians means to identify patients who may carry germline BAP1 mutations and thus could be at high risk of developing CM, UM, MM, RCC, and possibly other tumors. As part of a novel multidisciplinary approach, physicians, pathologists, and clinicians involved into diagnostics should be aware of the histological features and the spectrum of tumors associated with BAP1 loss. Further clinical, epidemiological, and functional studies are required to fully explain the roles of BAP1 and its interaction partners in neoplasia, to define mechanisms behind shared and non-shared clinical and pathological criteria.
PMCID: PMC4011723  PMID: 24855403
Bap1; cancer syndrome; melanoma; mesothelioma; MBAITs
22.  Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel—an Indirect Comparison 
This study aims to make an indirect comparison between enzalutamide and abiraterone acetate for mCRPC post-docetaxel.
A search for published phase 3 trials was performed with PubMed. Indirect comparisons of enzalutamide (AFFIRM) to abiraterone acetate (COU-AA-301) on outcomes overall survival (OS), time to prostate-specific-antigen (PSA) progression, radiographic progression-free survival (PFS), and PSA response were constructed in the context of log-linear regression models.
There was no statistically significant difference in OS (hazard ratio (HR) 0.85, 95% CI 0.68–1.07). However, there was some evidence that enzalutamide may outperform abiraterone acetate with respect to secondary outcomes: time to PSA progression (HR 0.40, 95% CI 0.30–0.53), radiographic PFS (HR 0.61, 95% CI 0.50–0.74), and PSA response rates (RRs) (OR 10.69, 95% CI 3.92–29.20).
While there was no statistically significant difference in OS, enzalutamide may be advantageous for secondary endpoints. Findings of this indirect comparison serve to be hypothesis-generating for future head-to-head trials.
PMCID: PMC3964205  PMID: 24678245
enzalutamide; abiraterone acetate; metastatic castration-resistant prostate cancer; mCRPC; post-docetaxel
23.  Impact of Gender in Renal Cell Carcinoma: The Relationship of FABP7 and BRN2 Expression with Overall Survival 
To investigate the relationship between gender differences in fatty acid-binding protein7 (FABP7) and BRN2 (POU class 3 homeobox 2) expression in renal cell carcinoma (RCC) and the prognosis of patients with RCC.
immunohistochemical (IHC) staining as well as reverse transcription-polymerase chain reaction (RT-PCR) was performed in renal tissues from 103 patients (83 men, mean age = 63.6 years old; 20 women, mean age = 63.1 years old) underwent radical nephrectomy from January 1, 2001 through December 31, 2010. The probability of overall patient survival was estimated using the Kaplan-Meier method.
FABP7 mRNA expression was more frequent in men (P = 0.07) while BRN2 protein expression was significantly more frequent in women (P = 0.029). In particular, FABP7 was expressed in 100% of G1 renal cell carcinoma both in mRNA and protein levels. In women, FABP7 (−) and BRN2 (+) groups had a worse prognosis both in mRNA level (P = 0.038) and protein level (P = 0.058). BRN2 was expressed 100% of papillary RCC both in mRNA and protein levels.
Our results demonstrated that gender was a key factor in FABP7 and BRN2 expression in RCC, and the combination with FABP7 and BRN2 stratified by gender could be a new potential prognostic factor in patients with RCC.
PMCID: PMC3937181  PMID: 24653654
BRN2; FABP7; gender; overall survival; renal cell carcinoma
24.  Folate Levels and Polymorphisms in the Genes MTHFR, MTR, and TS in Colorectal Cancer 
The aim of the study was to explore and describe the effect of polymorphisms in folate-associated genes regarding the levels of different folate forms and their distribution in tumors and mucosa in patients with colorectal cancer.
Tumor and mucosa tissues from 53 patients with colorectal cancer were analyzed. The concentrations of tetrahydrofolate (THF), 5-methylTHF, and 5,10-methyleneTHF were measured by liquid chromatography—mass spectrometry. Genotyping of polymorphisms in the folate-associated genes methylenetetrahydrofolate reductase (MTHFR, C677T), methionine synthase (MTR, A2756G), and thymidylate synthase (TS, 5′-TSER 28 bp tandem repeat and 3′-TSUTR 6 bp deletion/insertion), were done by real-time polymerase chain reaction. Folate levels and distributions were determined in the total patient cohort and after subgrouping by genotypes.
The total folate level, as well as the THF and 5,10-methyleneTHF levels, were significantly higher in the tumor compared with mucosa tissue (P = 0.030, 0.031, and 0.015, respectively). The individual variation in folate levels in both tumor and mucosa were larger than the variation found when the patients were subgrouped by the gene polymorphisms. No significant differences in the mean concentration of any folate in the mucosa or tumor tissue were found in relation to the analyzed polymorphisms. The percentage level of 5,10-methyleneTHF in tumors was highest in patients with the MTHFR 677 CC genotype, and lowest in patients with the TT genotype (P = 0.033). A significantly lower percentage level of the 5,10-methyleneTHF level was found in tumors of patients with the 5′-TSER 3R/3R genotype (P = 0.0031).
A significant difference was found between the percentage level of 5,10-methyleneTHF in tumor tissues in relation to the MTHFR C677T and 5′-TSER 28 bp repeat polymorphisms. However, no differences were found in the actual tissue folate levels, or in their distribution, in relation to the polymorphisms in the MTHFR, MTR, or TS genes. These findings could be of importance for further research in the field by explaining some of the difficulties of obtaining reproducible and uniform results when using a few selected polymorphisms as predictive markers.
PMCID: PMC3937179  PMID: 24596472
colorectal cancer; folate levels; gene polymorphisms
25.  Comparing the Metal Concentration in the Hair of Cancer Patients and Healthy People Living in the Malwa Region of Punjab, India 
The cancer prevalence in the Malwa region of Punjab (1089/million/year) is much higher than the national average cancer prevalence in India (800/million/year). The participants in the present study were 50 healthy individuals and 49 cancer patients all living in the Malwa region of Punjab, with the healthy people being selected from the same household as the cancer patients. High concentrations of several potentially toxic elements were found in hair samples from people living in Punjab. Compared to standard reference ranges, the metals in excess in both the control and patient groups were aluminium (Al), barium (Ba), manganese (Mn), strontium (Sr) and uranium (U). The most significant findings were high lead (Pb), U and Ba concentrations. The maximum values for Ba, Mn, Pb and U were found in hair from breast cancer patients. The mean concentration of U in hair from the breast cancer patients was 0.63 μg U/g, which is more than double the value found in the control group and over six times higher than the reference range of 0.1 μg U/g. Water, soil, and phosphate fertilizers all seem to play a potential role, causing an increased metal burden in Punjabi people living in the Malwa region. The present study indicates that metals, and especially U, may be a factor in the development of breast cancer among Punjabi women.
PMCID: PMC3891755  PMID: 24453505
Punjab; Malwa region; cancer; breast cancer; hair analysis; barium; lead; strontium; uranium

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