Critical reviews in oncology/hematology

Publications in this journal

• Article: Cancer in developing countries: The next most preventable pandemic. The global problem of cancer.

  Miriam López-Gómez, Eduardo Malmierca, Miguel de Górgolas, Enrique Casado
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  ABSTRACT: Cancer is a global problem that accounts for almost 13% of deaths worldwide, a number similar to the 7 million deaths each year from HIV/AIDS, TB and malaria combined According to Globocan it is estimated that by 2020, there will be between 15 and 17 million new cases of cancer every year, 60% of which will be in developing countries. Moreover, the survival rates in these regions are often half those of developed countries. However, cancer is potentially the most preventable disease; with current resources, one-third of tumors could be preventable, and another one-third of newly diagnosed cancer patients could experience increased survival or early-stage detection. There have been proposed several strategies and programs to ameliorate cancer prevention and treatment in less developed countries. If all these proposed strategies are taken into consideration, worldwide cancer care, control and survival in low-income countries may improve in the years to come.
  Critical reviews in oncology/hematology 04/2013;
• Article: The systemic inflammation-based neutrophil-lymphocyte ratio: Experience in patients with cancer.

  Graeme J K Guthrie, Kellie A Charles, Campbell S D Roxburgh, Paul G Horgan, Donald C McMillan, Stephen J Clarke
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  ABSTRACT: There is increasing and consistent evidence that cancer-associated inflammation is a key determinant of outcome in patients with cancer. Various markers of inflammation have been examined over the past decade in an attempt to refine stratification of patients to treatment and predict survival. One routinely available marker of the systemic inflammatory response is the neutrophil-lymphocyte ratio (NLR), which is derived from the absolute neutrophil and absolute lymphocyte counts of a full blood count. To date, over 60 studies (>37,000 patients) have examined the clinical utility of the NLR to predict patient outcomes in a variety of cancers. The present systematic review examines and comments on the clinical utility of the NLR. The NLR had independent prognostic value in (a) unselected cohorts (1 study of >12,000 patients), (b) operable disease (20 studies, >4000 patients), (c) patients receiving neoadjuvant treatment and resection (5 studies, >1000 patients), (d) patients receiving chemo/radiotherapy (12 studies, >2000 patients) and (e) patients with inoperable disease (6 studies, >1200 patients). These studies originated from ten different countries, in particular UK, Japan, and China. Further, correlative studies (15 studies, >8500 patients) have shown that NLR is elevated in patients with more advanced or aggressive disease evidenced by increased tumour stage, nodal stage, number of metastatic lesions and as such these patients may represent a particularly high-risk patient population. Further studies investigating the tumour and host-derived factors regulating the systemic inflammatory response, in particular the NLR, may identify novel treatment strategies for patients with cancer.
  Critical reviews in oncology/hematology 04/2013;
• Article: Supportive care needs of hematological cancer survivors: A critical review of the literature.

  Alix Hall, Marita Lynagh, Jamie Bryant, Rob Sanson-Fisher
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  ABSTRACT: The purpose of this review was to determine the perceived supportive care needs of hematological cancer survivors, and the patient characteristics associated with higher levels of need. Medline, PsychInfo, CINAHL, EMBASE and PsycEXTRA, were searched for eligible articles published between 1979 and 2011. Ten full-text articles were identified. Extensive variation among study populations, methodologies and needs assessment measures used, made it difficult to synthesize results. Consequently, we could not confidently determine the most prevalent perceived needs of hematological cancer survivors. However, the limited data loosely suggests that concerns surrounding cancer recurrence and survival may be predominant needs experienced by hematological cancer survivors. Younger survivors were also identified by several studies as reporting higher levels of several areas of need. Future research is needed to assess the supportive care needs of large heterogeneous, population-based samples of hematological cancer survivors, utilizing valid, reliable and standardized measures of supportive care needs.
  Critical reviews in oncology/hematology 04/2013;
• Article: HER2 status for prognosis and prediction of treatment efficacy in adenocarcinomas: A review.

  Constance Thibault, Wassim Khodari, Marie Lequoy, Joseph Gligorov, Yazid Belkacémi
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  ABSTRACT: The past few years have seen flourish new biologic parameters for cancer prognosis that are revolutionizing therapeutic strategies. HER-2 is in this perspective a striking example, as it is now a key element for the care of 15-20% of breast cancer. HER-2 overexpression has first been reported as a prognostic factor before its consideration as a main parameter to predict treatment efficacy. However, although HER-2 status is now also used as a prognostic factor for many cancers, its ability to predict the action of trastuzumab in these new contexts is much lower than in breast cancer. In this literature review, we aimed to discuss HER-2 overexpression as a prognostic factor and as a predictive parameter of treatment response in selected solid tumors with a focus on adenocarcinomas.
  Critical reviews in oncology/hematology 04/2013;
• Article: Mismatch repair status and clinical outcome in endometrial cancer: A systematic review and meta-analysis.

  Ivan Diaz-Padilla, Nuria Romero, Eitan Amir, Xavier Matias-Guiu, Eduardo Vilar, Franco Muggia, Jesus Garcia-Donas
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  ABSTRACT: BACKGROUND: The association between the deficiency in mismatch repair (MMR) genes and prognosis in women with endometrial cancer is unclear. Here we report a systematic review and meta-analysis exploring this association. METHODS: We searched literature databases (MEDLINE, EMBASE, and Cochrane) from 1980 until December 2011 to identify studies evaluating the association between MMR status and clinical outcome in endometrial cancer. The main outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: Twenty-three studies met the inclusion criteria. The median sample size of studies was 112, 74% were retrospective case-series and 70% performed microsatellite instability (MSI) analysis to evaluate the status of MMR. Only 22% of studies used the panel of five microsatellite markers recommended by the National Cancer Institute. Seven studies used immunohistochemistry to define MMR deficiency, but only two of them determined the expression of all four MMR proteins. Overall, significant associations between MMR and outcome were observed in 32% of studies. There was marked inter-study heterogeneity for estimates of OS and DFS. Pooled analysis did not show any significant association between deficiency in MMR and worse OS (6 studies, hazard ratio [HR] 2.0, p=0.11) or DFS (4 studies, HR ratio 1.31, p=0.66). CONCLUSION: There is no definitive evidence of a significant association between MMR status and detrimental survival in endometrial cancer.
  Critical reviews in oncology/hematology 04/2013;
• Article: Anti-thymocyte globulins for post-transplant graft-versus-host disease prophylaxis-A systematic review and meta-analysis.

  Sebastian Theurich, Hans Fischmann, Geothy Chakupurakal, Alexander Shimabukuro-Vornhagen, Jens M Chemnitz, Udo Holtick, Achim Rothe, Christof Scheid, Michael Hallek, Nicole Skoetz, Michael von Bergwelt-Baildon
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  ABSTRACT: BACKGROUND: Despite advances made in allogeneic hematopoietic stem cell transplantation (alloSCT), graft versus host disease (GvHD) remains a major problem. The main strategy to combat GvHD is prophylaxis and ATG plays a major role in this arena. Conflicting reports on the effectiveness of ATG on GvHD prevention prompted us to address this question by means of a systematic review and meta-analysis. METHODS: Six prospective randomized controlled trials (RCT) comparing the addition of ATG to standard immunosuppressive regimen as GvHD prophylaxis were analyzed. All ATG preparations were considered but homogeneity in type of preparation and dosage had to be observed within each trial. RESULTS: Our meta-analysis reveals that the incidence of grade II-IV GvHD was significantly lower in patients receiving ATG. Addition of ATG had no impact on overall survival, relapse or non-relapse mortality. CONCLUSIONS: Based on the current level of the data analyzed in this systematic review, we cannot conclude a general recommendation for the use of ATG for GvHD prophylaxis in alloSCT. In patients who are at high risk for severe GvHD it should be considered individually. However, due to the heterogeneity of the analyzable studies it seems likely that future studies might change the results of the pooled data of this meta-analysis. In order to improve the current level of data, further randomized studies in this topic are therefore urgently warranted.
  Critical reviews in oncology/hematology 04/2013;
• Article: A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapies.

  G Ranieri, C D Gadaleta, R Patruno, N Zizzo, M G Daidone, M G Hansson, A Paradiso, D Ribatti
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  ABSTRACT: Murine cancer models have been extremely useful for analyzing the biology of pathways involved in cancer initiation, promotion, and progression. Interestingly, several murine cancer models also exhibit heterogeneity, genomic instability and an intact immune system. However, they do not adequately represent several features that define cancer in humans, including long periods of latency, the complex biology of cancer recurrence and metastasis and outcomes to novel therapies. Therefore, additional models that better investigate the human disease are needed. In the pet population, with special references to the dog, cancer is a spontaneous disease and dogs naturally develop cancers that share many characteristics with human malignancies. More than 40 years ago, optimization of bone marrow transplantation protocols was undertaken in dogs and recently novel targeted therapies such as liposomal muramyl tripeptide phosphatidylethanolamine and several tyrosine kinase inhibitors, namely masitinib (AB1010) and toceranib phosphate (SU11654), have been developed to treat dog tumors which have then been translated to human clinical trials. In this review article, we will analyze biological data from dog tumors and comparative features with human tumors, and new therapeutic approaches translated from dog to human cancer.
  Critical reviews in oncology/hematology 04/2013;
• Article: Current status and future directions in induction chemotherapy for head and neck cancer.

  Athanassios Argiris
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  ABSTRACT: As a component of multimodal therapy in locally advanced head and neck cancer, induction chemotherapy represents a strategy to reduce tumor burden and target distant metastases prior to definitive treatment. Although the addition of taxanes to the cisplatin and 5-fluorouracil induction regimen (TPF) has greatly benefitted outcomes in comparison with PF alone, recent phase III trials have not shown a survival advantage for TPF induction followed by chemoradiotherapy vs. chemoradiotherapy alone. While these trials may have been underpowered to demonstrate a survival benefit, additional phase III trials are ongoing, with highly anticipated results. "Next-generation" sequential regimens that include targeted agents such as cetuximab are emerging as an approach to increase activity while decreasing toxicity. In addition, patient selection based on individual disease characteristics may identify ideal candidates for induction therapy. These developments may result in personalized therapeutic regimens that improve clinical outcomes.
  Critical reviews in oncology/hematology 03/2013;
• Article: The role of the ubiquitin proteasome system in lymphoma.

  K Stephen Suh, Takemi Tanaka, Sreeja Sarojini, Ginah Nightingale, Rajendra Gharbaran, Andrew Pecora, Andre Goy
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  ABSTRACT: The ubiquitin-proteasome system (UPS) maintains the integrity of cellular processes by controlling protein degradation pathways. The role of the UPS in proliferation, cell cycle, differentiation, DNA repair, protein folding, and apoptosis is well documented, and a wide range of protein activities in these signaling pathways can be manipulated by UPS inhibitors, which include many anti-cancer agents. Naturally occurring and synthetic drugs designed to target the UPS are currently used for hematological cancers, including lymphoma. These drugs largely interfere with the E1 and E2 regions of the 26S proteasome, blocking proteasomal activity and promoting apoptosis by enhancing activities of the extrinsic (death receptors, Trail, Fas) and intrinsic (caspases, Bax, Bcl2, p53, nuclear factor-kappa B, p27) cell death programs. This review focuses on recent clinical developments concerning UPS inhibitors, signaling pathways that are affected by down-regulation of UPS activities, and apoptotic mechanisms promoted by drugs in this class that are used to treat lymphoma.
  Critical reviews in oncology/hematology 03/2013;
• Article: State of the art for cardiotoxicity due to chemotherapy and to targeted therapies: A literature review.

  Rossana Berardi, Miriam Caramanti, Agnese Savini, Silvia Chiorrini, Chiara Pierantoni, Azzurra Onofri, Zelmira Ballatore, Mariagrazia De Lisa, Paola Mazzanti, Stefano Cascinu
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  ABSTRACT: Cardiotoxicity is a common complication of many anti-cancer agents and it remains a major limitation, strongly impacting the quality of life and the overall survival, regardless of the oncologic prognosis. Cardiotoxicity may occur during or shortly after treatment (within days or weeks), or it may become evident months, and sometimes years, after completion of chemotherapy. Cardiotoxicity associated with cancer therapies can range from asymptomatic subclinical abnormalities, including electrocardiographic changes and temporary left ventricular ejection fraction decline, to life-threatening events such as congestive heart failure or acute coronary syndromes. The aim of this review is to summarize potential cancer chemotherapeutics-related cardiovascular toxicities in adult cancer-patients and to suggest monitoring and treatment options for each agent, that can serve as a tool in the clinical practice.
  Critical reviews in oncology/hematology 03/2013;
• Article: Biomolecular markers of cancer-associated thromboembolism.

  Diana L Hanna, Richard H White, Ted Wun
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  ABSTRACT: Venous thromboembolism (VTE; deep venous thrombosis and pulmonary embolism) is associated with a poor prognosis in most malignancies and is a major cause of death among cancer patients. Universal anticoagulation for primary thromboprophylaxis in the outpatient setting is precluded by potential bleeding complications, especially without sufficient evidence that all patients would benefit from such prophylaxis. Therefore, appropriately targeting cancer patients for thromboprophylaxis is key to reducing morbidity and perhaps mortality. Predictive biomarkers could aid in identifying patients at high risk for VTE. Possible biomarkers for VTE include C-reactive protein, platelet and leukocyte counts, D-dimer and prothrombin fragment 1+2, procoagulant factor VIII, tissue factor, and soluble P-selectin. Evidence is emerging to support the use of risk assessment models in selecting appropriate candidates for primary thromboprophylaxis in the cancer setting. Further studies are needed to optimize these models and determine utility in reducing morbidity and mortality from cancer-associated thromboembolism.
  Critical reviews in oncology/hematology 03/2013;
• Article: mTOR inhibitors in advanced renal cell carcinomas: From biology to clinical practice.

  Philippe Barthélémy, Benjamin Hoch, Christine Chevreau, Florence Joly, Brigitte Laguerre, François Lokiec, Brigitte Duclos
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  ABSTRACT: To date, oral everolimus is indicated for the treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with vascular endothelial growth factor-targeted therapy, and intravenous temsirolimus for the first-line treatment of patients with poor prognosis metastatic renal cell carcinoma. However, some factors could guide the treatment choice aiming to individualize a treatment plan. Besides the crucial issue of treatment efficacy, other factors are to be considered such as disease status, histological subtype, extent of the disease, patient-specific factors, and agent-specific factors. All of these considerations have to stay in the frame of guideline recommendations which represent evidence-based medicine. The purpose of this article is to summarize the main pharmacological and pharmacokinetic characteristics of mTOR inhibitors, and to define targeted populations according to prognostic indexes.
  Critical reviews in oncology/hematology 03/2013;
• Article: The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer.

  Francesco Torino, Roberta Sarmiento, Giampietro Gasparini
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  ABSTRACT: Neoadjuvant chemoradiation therapy is a commonly used option aimed to make less aggressive surgery approaches and to improve quality of life allowing a high proportion of patients operated with sphincter-sparing surgical techniques in locally advanced rectal cancer (LARC). During the last 5 years a number of studies have tested the efficacy of more intensive chemotherapeutic approaches by combining irinotecan or oxaliplatin with fluoropyrimidines and standard radiation treatments as well as testing combined treatments with targeted agents directed against epidermal growth factor receptor (EGFR) or angiogenesis. Herein, we review the results and critiques of the published studies based on the introduction of novel targeted agents in neoadjuvant therapy of LARC.
  Critical reviews in oncology/hematology 03/2013;
• Article: Primary renal carcinoid: Treatment and prognosis.

  Taner Korkmaz, Selcuk Seber, Dilek Yavuzer, Mahmut Gumus, N Serdar Turhal
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  ABSTRACT: Primary carcinoid tumors of the kidney are very rare, malignant tumors consisting of neuroendocrine cells. The pathogenesis of renal carcinoid is unclear because neuroendocrine cells are not normally found in adult renal parenchyma. Electron microscopy, immunohistochemistry, octreotide scan, positron emission tomography along with conventional radiographic imaging techniques are used in diagnosis and follow-up. Presenting symptoms usually include flank pain and haematuria. Early stage disease is treated with surgery only. However, randomized trials are lacking because of the very low number of reported cases. Thus, the role of debulking surgery, chemotherapy, radiotherapy, octreotide and targeted therapy in the management of advanced disease remains an open question. In this article the clinicopathologic features and prognosis of this very rare disease along with treatment outcomes of the reported cases are reviewed. In addition, we report a new case of a metastatic primary renal atypical carcinoid tumor treated with octreotide therapy.
  Critical reviews in oncology/hematology 03/2013;
• Article: The treatment of glioblastomas: A systematic update on clinical Phase III trials.

  An-An Yin, Jin-Xiang Cheng, Xiang Zhang, Bo-Lin Liu
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  ABSTRACT: Glioblastomas (GBMs) are invariably associated with unavoidable tumor recurrence and overall poor prognosis. The present study is to summarize the results of clinical Phase III studies on GBMs over the past seven years. A systematic literature search was performed using major electronic databases and by screening meeting abstracts. Totally, 16 studies of patients with newly diagnosed GBMs, recurrent GBMs, and elderly patients with GBMs were selected for this review. Although the outcomes of the experimental therapies were not encouraging, these studies produced a considerable amount of potentially clinically relevant information. Such aspects as surgical outcomes, radiation schedules, temozolomide (TMZ) schedules, methylation status of the O6-methylguanine DNA methyltransferase (MGMT) gene, combination of therapies, novel drug delivery methods and use of targeted agents have come to light and are being addressed here. In addition, we discuss the existing controversies of (1) surgical studies, (2) evaluations of recurrence, (3) salvage treatment bias, and (4) studies on elderly patients.
  Critical reviews in oncology/hematology 02/2013;
• Article: The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy.

  Erik Wibowo, Richard J Wassersug
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  ABSTRACT: Androgen deprivation therapy (ADT) for prostate cancer (PCa) treatment causes sexual dysfunction. We review here the effects of estrogen on the sexual performance of androgen-deprived males. The major findings are: We discuss the general benefits of estrogen therapy to quality of life of men on ADT, the potential risks of this treatment, and possible treatment regimes for estrogen therapy in males. Unless contraindicated, we propose that PCa patients on ADT would benefit from supplemental parenteral estrogen.
  Critical reviews in oncology/hematology 02/2013;
• Article: The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer.

  Vladimir N Anisimov, Andrzej Bartke
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  ABSTRACT: Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. GH/Insulin/insulin-like growth factor-1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases lifespan in nematodes, fruit flies and mice. The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both lifespan extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore, metformin seems to decrease the risk for cancer in diabetic patients.
  Critical reviews in oncology/hematology 02/2013;