Showing papers in "Current Opinion in Oncology in 2005"

Doctor-patient communication and satisfaction with care in oncology.

Abstract: Purpose of reviewThis review summarises current knowledge on the impact on patient satisfaction of initiatives undertaken to enhance the communication between doctors and their patients in oncology.Recent findingsRecent studies have assessed the effectiveness of different approaches aimed at improvi

Patient-physician communication in oncology: past, present, and future.

Abstract: Purpose of reviewContemporary oncology practice acknowledges the importance of partnering with the patient and family in dealing with the illness. Patients also value their physicians as important sources of support when they provide information about the illness, encouragement, and hope, discuss tr

DNA methylation and cancer therapy: new developments and expectations.

Abstract: Purpose of reviewIn addition to having genetic causes, cancer can also be considered an epigenetic disease. The main epigenetic modification is DNA methylation, and patterns of aberrant DNA methylation are now recognized to be a common hallmark of human tumors. One of the most characteristic feature

Duel nature of TGF-beta signaling: tumor suppressor vs. tumor promoter.

Abstract: Purpose of reviewTransforming growth factor β type I (TGF-β) is a ubiquitous cytokine that is well known for its ability to inhibit epithelial cell proliferation. Somatic mutations abrogating the TGF-β signal transduction pathway are found in many gastrointestinal cancers, confirming its importance

Communication skills training in cancer care: where are we and where are we going?

Abstract: Purpose of reviewThis review gives an overview of recent developments in the field of communication skills training programs designed for cancer health care professionals.Recent findingsThe Web of Knowledge was searched for empirical papers published between January 2002 and February 2005. Twenty-tw

Systems biology for cancer.

Abstract: Purpose of review Significant insight can be gained into complex biologic mechanisms of cancer via a combined computational and experimental systems biology approach. This review highlights some of the major systems biology efforts that were applied to cancer in the past year. Recent findings Two main approaches to computational systems biology are discussed: mechanistic dynamical simulations and inferential data mining. Significant developments have occurred in both areas. For example, mechanistic simulations of the EGFR pathway are promoting understanding of cancer, and Bayesian inference approaches allow for the reconstruction of regulatory networks. In addition, the article reports on advancements in experimental systems biology for determining protein-protein interactions and quantifying protein expression to generate the necessary data for computational modeling and inferential data mining. Emerging approaches will further improve the ability to bridge the gap between in vitro systems and in vivo human biology. Technologies paving the way include in vitro models that better reflect in vivo tumors, microfabricated devices of human physiology, and improved animal models. Summary An important challenge facing the field is how better to translate in vitro discoveries to the clinic. Computational systems biology approaches that use omic data to predict biology along with novel experimental systems that better represent human in vivo biology will prove useful in bridging this gap. Although still early, the potential application of systems biology and the future evolution of the field will significantly affect understanding of cancer disease mechanisms and the ability to devise effective therapeutics.

Communication in palliative care: a review of recent literature.

Abstract: Purpose of review The quality of communication with patients, family, and team members is an extremely important element in palliative cancer care. The current paper reviews the literature on these topics as published in 2004. Recent findings Trust was found to be a major factor for relationship building. Information gathered by patient self-report is the method of choice, given improved insight in symptom prevalence, duration, frequency, and interference. Cultural factors in information giving, the optimal process and content, and the difficulty of conveying hope were addressed. Decision making in palliative care requires a complex integration of conceptual knowledge, ethical and legal implications, and communication skills. Aspects of manageability are explored. Although health care providers must communicate about emotions, the existential distress of cancer patients and carers often goes overlooked in the last phases of life. Summary Themes included the education of health care providers, the need to care for carers, and interdisciplinary communication. Little attention was given to the growing population of elderly patients. Observer-based studies are unfortunately scarce, making the practice of palliative communication unseen. Finally, few studies report the cost-effectiveness of palliative care interventions though such studies may enhance palliative care and convince policy makers of the need to support such care. More empirical work is needed to improve the level of quality needed to ensure a good remaining lifetime for cancer patients whose disease cannot be cured.

Dermoscopy for skin cancer detection.

Abstract: Tomographic imaging of soft tissue such as skin has a potential role in cancer detection. The penetration of infrared wavelengths makes a confocal approach based on laser feedback interferometry feasible. We present a compact system using a semiconductor laser as both transmitter and receiver. Numerical and physical models based on the known optical properties of keratinocyte cancers were developed. We validated the technique on three phantoms containing macro-structural changes in optical properties. Experimental results were in agreement with numerical simulations and structural changes were evident which would permit discrimination of healthy tissue and tumour. Furthermore, cancer type discrimination was also able to be visualized using this imaging technique.

Update on angiogenesis inhibitors.

Abstract: Purpose of reviewA number of therapeutic agents have been developed which have anti-angiogenic potential. Here we present the most recent data from clinical trials with some of the promising inhibitors of angiogenesis.Recent findingsAgents that target the vascular endothelial growth factor signaling

Low-level laser for prevention and therapy of oral mucositis induced by chemotherapy or radiotherapy.

Abstract: Purpose of review Oral mucositis is a common morbid condition associated with chemotherapy or radiotherapy for which there is no standard prophylaxis or treatment. There is increasing evidence that the use of low-level laser can reduced the severity of mucositis associated with chemotherapy or radiation therapy. The purpose of this review is to examine the available evidence for it. Recent findings For most approaches commonly used to prevent or treat chemotherapy-associated or radiotherapy-associated oral mucositis, a recent panel of experts could not find sufficient levels of evidence to recommend or suggest their use. As for low-level laser therapy, the results are difficult to assess and compare because of interoperator variability and because clinical trials are difficult to conduct in that field. Nevertheless, there is accumulating evidence in support of low-level laser therapy. Summary On the basis of literature data, it is reasonable to conclude that the evidence that low-level laser therapy may be useful in decreasing the severity of chemotherapy-associated or radiotherapy-associated mucositis is substantial, even though there have been few controlled studies in the field of prevention.

Basal cell nevus syndrome.

Abstract: Purpose of review Basal cell nevus syndrome (BCNS), is a hereditary condition transmitted as an autosomal dominant trait exhibiting high penetrance and variable expressivity. Inherited or spontaneous mutations in the human homologue of the Drosophila patched gene underlie the disorder and in addition to tumor predisposition, are associated with a range of ‘patterning’ defects. Recent advances, with glimpses of possible therapies are emerging, but because of the wide-ranging nature of phenotypic expression and overlap with other syndromes, there is difficulty. Finally, because of the importance of PTCH and paralogous genes in many species other than humans, reports appear in a correspondingly wide range of journals, which makes ‘keeping abreast’ difficult. Recent findings Progress has been achieved in understanding the role of Gli-1, 2, & 3 in development of ‘sporadic’ BCCs and BCNS. Expression of PTCH1 is now known to be regulated by alternative promoters and a single functional Gli-binding site. Expression of FOXE1 as a new transcriptional target of Gli2 has been demonstrated in human epidermis and BCCs. Finally, the discovery of Shh pathway inhibitors such as cyclopamine, a naturally occurring alkaloid and ornithine decarboxylase inhibition suggest possible interventional therapies. Summary In BCNS, phenotype does not correlate with position of mutations within Patched, suggesting genetic makeup and environment modulate effects of premature protein truncation induced by PTCH mutation. These developmental abnormalities occur as a result of haplo-insufficiency in heterozygotes for the mutated gene, whereas neoplastic complications arise from a classical two-hit tumor suppressor gene model. Attention is therefore turning toward TP53 and PTCH associations.

Biomarkers for prediction of sensitivity to EGFR inhibitors in non-small cell lung cancer

Abstract: PURPOSE OF REVIEW Epidermal growth factor receptor (EGFR) Inhibitors have shown promising results in patients with advanced non-small cell lung cancers (NSCLC) who previously have failed on chemotherapy. Objective response is achieved in 10 to 28% of the patients, and about 30% will achieve stable disease. A major problem is how to select the patients, who will benefit from treatment, and who will not. RECENT FINDINGS The predictive role of EGFR protein expression assessed by IHC is still debated. Specific EGFR gene mutations have been identified associated with response to gefitinib (Iressa(R)), but seem not to be associated with stable disease. No studies have yet demonstrated any association between EGFR gene mutations and survival. In this review we describe other marker studies, which are associated with sensitivity to EGFR inhibitors. Increased EGFR gene copy number based on FISH analysis is demonstrated to be a good predictive marker for response, stable disease, time to progression, and survival. SUMMARY EGFR/FISH seems today to be the best predictive marker for clinical benefit from EGFR inhibitors in NSCLC. Prospective large scale clinical studies must identify the most optimal paradigm for selection of patients.

The role of surgery in ovarian cancer with special emphasis on cytoreductive surgery for recurrence.

Abstract: Purpose of review The role of cytoreductive surgery for recurrent ovarian cancer has not clearly been defined, and randomized trials are lacking. Some series have reported favorable outcomes for selected patients. This review summarizes the available evidence for selecting patients and the results of cytoreductive surgery in recurrent ovarian cancer. Recent findings A Medline search identified 23 series including 1795 patients (21-285 patients per study). Patients who underwent cytoreductive surgery for recurrence were highly selected. Complete tumor resection was feasible in 9 to 82% of patients and was commonly associated with prolonged survival. A variety of predictive and prognostic factors for complete resection were reported. Good performance status, disease characteristics (e.g. peritoneal carcinosis), and outcome of prior surgery seemed to have an impact on surgical outcome. By contrast, disease-free survival played only a minor role, especially in patients with recurrence later than 6 months after primary treatment. Summary Prospective evaluation of predictive scores for successful cytoreductive surgery in recurrent ovarian cancer is urgently needed. In a second step, randomized trials evaluating the role of surgery in the treatment strategy of recurrent ovarian cancer should be initiated. Until then, experienced and trained surgeons might offer surgery for recurrent disease to individually selected patients after giving information about the potential benefit and about the limited available evidence regarding this strategy.

Angiogenesis in malignant lymphoma.

Abstract: PURPOSE OF REVIEW: Angiogenesis plays an important role in the pathophysiology of both solid tumors and hematologic malignancies Angiogenesis-associated parameters are important prognosticators, and tumor blood vessels are an emerging target for therapy This review addresses the evidence of the role of angiogenesis in malignant lymphoma and discusses some therapeutic implications RECENT FINDINGS: In angiogenesis assays, lymphoma cells show angiogenic properties Tumor vascularization is higher in lymphoma tissue than in reactive lymph nodes and increases in step with clinically more aggressive lymphoma subtypes and advanced-stage disease High levels of vascular endothelial growth factor in blood and tissue are associated with adverse prognosis Vascular endothelial growth factor and vascular endothelial growth factor receptors are also present in lymphoma cells Therapy against vascular endothelial growth factor in animal models is effective and points to both the tumor cell and the host endothelium as targets Structural microvessel abnormalities are present in some lymphoma subtypes The role of angiogenesis might vary in lymphoma subtypes because the prognostic value of microvessel density and the expression of angiogenesis-related molecules differ between lymphoma subtypes There are also differences in blood vessel phenotype between lymphoma subtypes This heterogeneity may have implications for antiangiogenic therapies Antiangiogenic therapy in human lymphoma is still in its infancy SUMMARY: The role of angiogenesis in malignant lymphoma is evident Tumor vasculature is an attractive target for lymphoma therapy Differences between lymphoma subtypes must be taken into account in the selection of the most suitable patients for trials with antiangiogenic agents

Multiple endocrine neoplasia syndrome: genetic basis for clinical management.

Abstract: Purpose of review Multiple endocrine neoplasia (MEN) types 1 and 2 are rare hereditary cancer syndromes expressing a variety of mainly endocrine neoplasias. Improved understanding of the molecular and clinical genetics associated with these lesions will likely enhance the diagnosis and treatment of patients with these diseases. Recent findings The MEN1 gene causing MEN1 is a tumor suppressor gene and seems to act as a regulator of the transcriptional machinery. Novel genetic and diagnostic modalities tend to identify neoplastic lesions at an earlier stage, potentially improving outcome and quality of life. Improved understanding of genotype-phenotype correlations in MEN2, caused by a mutation in the RET oncogene, may enable a more individualized treatment for these patients. Summary Recent advances in molecular pathology, diagnosis, and management of patients with MEN1 and MEN2 are reviewed.

Mathematical modeling of tumorigenesis: mission possible.

Abstract: Purpose of review Mathematical modeling of tumorigenesis is a fast-growing area of research. This review describes recent (since July 2003) advances in this area and discusses possible implications for the field of cancer biology in general. Recent findings Broadly speaking, there are three major areas in which theory has contributed the most to cancer research: (1) modeling in the context of epidemiology and other statistical data, (2) mechanistic modeling of avascular and vascular tumor growth, and (3) modeling of cancer initiation and progression as somatic evolution. The first area uses models to fit the existing data, the second approach takes advantage of methods of physics and engineering to describe tumor growth, and the third method looks at cancer progression as a local, Darwinian evolution. Summary The article describes new, interesting ideas put forward in the last year, and suggests that to make the modeling effort more relevant, a better dialogue should be developed between theorists and experimental biologists. The author believes this is possible.

Adjuvant chemotherapy for soft tissue sarcoma.

Abstract: Purpose of review To review current state-of-the-art knowledge about adjuvant medical therapy in adult soft tissue sarcomas. Recent findings Most recent contributions have added nonrandomized evidence to previously available controlled clinical trials, which were undertaken from the 1970s. Again, results are conflicting, with a limited benefit suggested by some retrospective analyses and denied by others. While a delay in relapse is likely to occur in a fraction of patients treated with adjuvant chemotherapy, a permanent benefit has been more difficult to prove. This result is consistent with findings from previous clinical trials, which pointed to a slight benefit from Doxorubicin-based adjuvant chemotherapy and a possibly higher, although less evidence-based, benefit from anthracycline plus Ifosfamide regimens. Summary Overall, adjuvant chemotherapy may give some benefit in soft tissue sarcoma. If any, it is likely to be of limited degree, confined to the highest-risk patients, and requiring a fully active chemotherapy regimen. This was mainly shown for extremity soft tissue sarcoma but may also apply to other primary sites. The value of molecular-targeted therapy as an adjuvant for high-risk gastrointestinal stromal tumor patients is a different subject awaiting long-term results of ongoing trials.

Neuroendocrine tumors of the gastrointestinal tract: recent advances in molecular genetics, diagnosis, and treatment.

Abstract: Purpose of reviewNeuroendocrine tumors of the gastrointestinal tract represent a small area within oncology, but many new data have been reported during the past year. This paper updates the recent findings.Recent findingsAn N-terminally truncated variant of heat shock protein 70 (Hsp70) has been id

Targeting human herpesvirus-8 for treatment of Kaposi's sarcoma and primary effusion lymphoma.

Abstract: PURPOSE OF REVIEW: Human herpesvirus-8, also called the Kaposi's sarcoma herpesvirus, is present in all cases of Kaposi's sarcoma and primary effusion lymphoma and in some cases of multicentric Castleman's disease. This review discusses mechanisms by which human herpesvirus-8 contributes to tumorigenesis and how this knowledge can be used to target the virus for the treatment of these tumors. RECENT FINDINGS: Most primary effusion lymphomas and Kaposi's sarcoma tumor cells are latently infected with human herpesvirus-8 and hence resistant to antiherpesvirus drugs that are dependent on lytic replication. In contrast, many of the cells infected with human herpesvirus-8 in multicentric Castleman's disease support lytic replication, so that clinical improvement frequently occurs in response to treatment with antiherpesvirus drugs. The resistance of latently-infected tumor cells to antiherpesvirus drugs can be overcome by inducing human herpesvirus-8 to reenter the lytic cascade in the presence of antiherpesvirus drugs. This leads to apoptosis of virally infected cells without increasing production of infectious virus. Alternatively, the replication and maintenance of the human herpesvirus-8 episome during latency can be disrupted by glycyrrhizic acid or hydroxyurea so that the virus no longer contributes to tumorigenesis. Both the innate and acquired immune systems can also be augmented to help prevent or treat human herpesvirus-8-associated tumors. SUMMARY: Novel strategies targeting human herpesvirus-8, which is present in all cases of Kaposi's sarcoma and primary effusion lymphoma, provide opportunities for selectively killing tumor cells.

Treatment of malignant thymoma.

Abstract: Purpose of review The present review reports findings in the field of epithelial tumors originating from the thymus from the past year and discusses these findings in the context of the literature. Recent findings Epithelial tumors of the thymus are relatively common tumors of the anterior superior mediastinum. Thymomas are usually slowly growing tumors, and their prognosis depends on the macroscopic and microscopic invasion of surrounding tissues. Thymic carcinomas are more aggressive and less common tumors than thymomas and have been increasing in frequency in recent years. Surgery is the mainstay treatment of thymic malignancies, and complete resection represents the best prognostic factor in this disease. Postoperative radiotherapy may be indicated in tumors with invasion of surrounding tissues, but it is controversial in early-stage thymomas. Combination chemotherapy has been employed in several small studies and in advanced disease has been demonstrated to produce a 50-80% objective response rate. Neoadjuvant chemotherapy or external beam radiotherapy have been used with success in patients with tumors that are not readily resectable. Novel antiproliferative systemic agents are being investigated, based on a better understanding of the biology of these tumors. Summary A better understanding of the clinical behavior of thymomas versus thymic carcinomas and systemic therapies targeted to biologically validated targets in these diseases will help improve efficacy of treatment.

The changing face of invasive fungal infections in hematopoietic cell transplant recipients.

Abstract: Purpose of reviewTo review recent observations that describe changes in the likelihood of invasive fungal infections, shifts in types of fungal pathogens, and altered manifestations of fungal syndromes after hematopoietic cell transplantation and explore how changes in transplant practices are influ

Taxanes in the treatment of head and neck cancer.

Abstract: Purpose of reviewThis review presents new data on the role of paclitaxel and docetaxel in the management of squamous cell carcinoma of the head and neck. Recently both agents have been tested in squamous cell carcinoma of the head and neck in combination with other chemotherapeutic agents, targeted

Implications of treatment-induced mucosal barrier injury.

Abstract: PURPOSE OF REVIEW: This review highlights recent developments in the pathophysiology of treatment-induced mucosal barrier injury, outlines the application of new diagnostic tools, focuses on risk factors and complications, and offers an up-to-date overview on treatment options. RECENT FINDINGS: Treatment-induced mucosal damage is now thought to occur in five phases: initiation, up-regulation and message generation, amplification and signaling, ulceration, and healing. It is now possible to assess gut mucosal damage both by sugar permeability tests and serum citrulline. Amifostine reduces the oral mucositis of stem cell transplantation recipients after radiotherapy and high-dose chemotherapy. Palifermin (recombinant human keratinocyte growth factor 1), a trophic growth factor, has been shown to reduce significantly both the incidence and duration of severe mucositis after myeloablative therapy and may have the potential to reduce gut mucosal damage. SUMMARY: Treatment-induced mucosal barrier injury is a complex, dynamic pathobiological process manifested not only in the oral cavity but throughout the entire digestive tract, diminishing the quality of life and predisposing the patient to serious clinical complications. Therefore, it is important to detect mucosal damage induced by cytotoxic therapy adequately to be able to test the efficacy of new therapeutic options for preventing or ameliorating this complication.

Biology and therapy of mantle cell lymphoma.

Abstract: Purpose of reviewMantle cell lymphoma is an aggressive non-Hodgkin's lymphoma characterized by the t(11;14) chromosomal translocation and overexpression of cyclin D1. Constituting approximately 5 to 8% of all non-Hodgkin's lymphomas, it carries the poorest prognosis among non-Hodgkin's lymphoma subt

Advances in nasopharyngeal carcinoma.

Abstract: Purpose of review Intergroup 0099 established the role of concurrent chemotherapy with radiation therapy in the treatment of locally advanced nasopharyngeal carcinoma, but its reproducibility was unclear and chemotherapy compliance was poor. Multiple concurrent chemoradiation phase III trials were initiated in response to the Intergroup trial, and technologic advances in radiotherapy were explored to improve the therapeutic ratio. This review highlights recent advances in the management of nasopharyngeal carcinoma as a result of these endeavors. Recent findings Five randomized phase III trials confirmed the benefit of concurrent chemoradiation over radiation therapy alone, firmly establishing concurrent chemoradiation as the standard of care in locally advanced nasopharyngeal carcinoma. Each of these studies used conventional radiation therapy and noted an increase in toxicity over radiation therapy alone. Intensity-modulated radiation therapy is an advanced form of three-dimensional conformal radiotherapy which allows delivery of high doses of radiation to the tumor while sparing adjacent normal tissues, leading to improved local control and decreased radiation therapy-induced toxicities. Distant metastasis remains a significant problem despite intensity-modulated radiation therapy. Taxane-based induction chemotherapy seems promising in phase II studies. Targeted therapies remain a major area of interest and require further investigation. Summary Cisplatin-based concurrent chemoradiation followed by adjuvant chemotherapy is the standard of care for locally advanced nasopharyngeal carcinoma. Intensity-modulated radiation therapy has undergone a rapid evolution and is replacing conventional radiation therapy in many institutions. A multidisciplinary effort is under way to explore more effective systemic therapy to improve the distant metastasis free rates.

Apply innovative technologies to explore cancer genome.

Abstract: Purpose of reviewMolecular genetic alterations characterize the development of human cancer. Recent advances in molecular genetic technology and the success of the human genome project have empowered investigators with new tools in dissecting the cancer genome for discovery of new cancer-associated

Management of locally advanced cervical cancer.

Abstract: Purpose of reviewCervical cancer is a significant global public health problem. In underdeveloped countries where screening programs are not widely available and in underserved populations in developed countries, women commonly present with locally advanced disease that is not curable by any extent

Surgical considerations for management of distal extremity soft tissue sarcomas.

Abstract: Purpose of reviewThis review focuses on the surgical management of soft tissue sarcomas of the hands and the feet. With recent advances in limb salvage surgery and radiotherapy delivery, local control of soft tissue sarcoma in the extremity has become optimized, and the associated functional results

Psychosocial aspects of risk communication and mutation testing in familial breast-ovarian cancer.

Abstract: Purpose of reviewAs cancer genetics services develop, psychosocial research evaluating risk communication and mutation testing for familial breast-ovarian cancer has expanded rapidly. It is timely to review findings in key areas. These will inform risk counselling practice and help prepare women mak

Biomarkers for melanoma.

Abstract: Purpose of review Given the capricious nature of melanoma, biomarkers that provide significant insight into the behavior of melanoma would greatly aid in identifying patients at risk for disease progression, those whose disease has progressed subclinically, and those who would benefit from currently available systemic therapies This review focuses on molecular prognostic markers in primary melanoma, markers that aid in the detection of metastatic melanoma, and markers predictive of systemic therapy Recent findings Significant advances have been made in the field of melanoma biomarkers Utilization of paraffin-embedded tissue and multiple markers have improved the RT-PCR assays for detection of melanoma cells in lymph node tissue as well as peripheral blood Lymphangiogenesis has been identified as a novel mechanism for melanoma progression, and candidate markers in the NF-κB signaling pathway have been identified to play a key role in melanoma: tumor vasculature interactions Loss of heterozygosity has been used to identify potential candidates for biochemotherapy Furthermore, serum S100B protein has been shown to be superior to lactate dehydrogenase in predicting prognosis and response to treatment for patients with advanced melanoma Summary Although recent studies have contributed greatly to the development of melanoma markers, it is anticipated that the application of gene expression profiling and proteomics techniques to melanocytic neoplasms will result in the identification of even more effective biomarkers for melanoma than those currently in clinical use