Critical Reviews in Oncology / Hematology - Articles in Press

Colon cancer - Corrected Proof

2010-02-08

Abstract: Colon cancer is one of the leading tumours in the world and it is considered among the big killers, together with lung, prostate and breast cancer. In the recent years very important advances occurred in the field of treatment of this frequent disease: adjuvant chemotherapy was demonstrated to be effective, chiefly in stage III patients, and surgery was optimized in order to achieve the best results with a low morbidity. Several new target-oriented drugs are under evaluation and some of them (cetuximab and bevacizumab) have already exhibited a good activity/efficacy, mainly in combination with chemotherapy. The development of updated recommendations for the best management of these patients is crucial in order to obtain the best results, not only in clinical research but also in every-day practice. This report summarizes the most important achievements in this field and provides the readers useful suggestions for their professional practice.

Genomic Grade Index: An important tool for assessing breast cancer tumor grade and prognosis - Corrected Proof

Otto Metzger Filho, Michail Ignatiadis, Christos Sotiriou — 2010-02-08

Abstract: Different multi-gene expression signatures have been shown to outperform classic histopathologic variables and therefore represent an important step towards personalizing breast cancer treatment. In particular, gene profiles overcome many of the limitations observed with classic histopathologic variables. The Genomic Grade Index (GGI) is a gene expression signature developed to better define histologic grade assessment. GGI divides classic histologic grade into low and high risk, instead of grades 1, 2 and 3. The ability of GGI to predict response to chemotherapy and separate hormone receptor positive breast cancer subtypes has also been demonstrated. This article critically reviews the limitations inherent in classic histologic grade evaluation; it also reviews the process of gene signature development in general and then focuses on GGI, its biologic significance, comparison with different gene signatures, and its applicability to clinical practise.

Tomorrow's targeted therapies in breast cancer patients: What is the risk for increased radiation-induced cardiac toxicity? - Corrected Proof

2010-02-08

Abstract: Ongoing clinical trials are now investigating the benefits of new targeted therapies, including ErbB and tyrosine kinase inhibitors (TKI) and antiangiogenics. Those may carry a potential risk for additional cardiac toxicity, particularly in association with radiotherapy. Although the risk of symptomatic cardiotoxicity is low, more subtle functional declines may increase mortality with longer follow-up and necessitate caution when assessing concurrent or sequential trastuzumab or lapatinib with radiotherapy. Potential additive toxicity encourages more conformal irradiation modalities minimizing cardiac dose, such as gating, intensity-modulated radiotherapy or Helical Tomotherapy. We recommend the collection of substantial information relevant to cardiac radiotoxicity in further clinical trials of targeted agents in breast cancer treatment, including doses delivered to cardiac structures, especially the coronary arteries. The incorporation of new biomarkers or modalities for assessment of cardiac function may also become necessary to detect cardiac toxicity at earliest stage.

Emerging role of small ribonucleic acids in gastrointestinal tumors - Corrected Proof

Iuliana Shapira, Keith Sultan, Bhoomi Mehrotra, Daniel R. Budman — 2010-02-08

Abstract: Small regulatory ribonucleic acids (RNAs) are recently recognized as being connected with a growing list of common diseases such as: cancer, heart disease, diabetes and inflammation and to date more than 5,000 publications are recorded on PubMed alone. Specific pathways generate each class of RNAs and their activities converge in the process of silence interference.In gastrointestinal malignancies microRNAs are deregulated, sometimes found in higher or lower levels depending on the type of malignancy and stage of the disease, functioning either as tumor suppressors or as oncogenes they interact forming regulatory loops with known transcription factors and signaling pathways. MiRNAs extracted from archived tissue biopsies can be used effectively as diagnostic, prognostic tools and molecular markers because they are stable over time and resistant to RNAse degradation. The distinct physiology of small RNAs may translate in more targeted cancer therapies in the near future.

Adjuvant endocrine therapy in postmenopausal breast cancer patients: Does hormone receptor status influence decision-making? - Corrected Proof

Fabio Puglisi, Alessandro Marco Minisini — 2010-02-04

Abstract: Hormonal therapy, such as tamoxifen (TAM), is the cornerstone of adjuvant treatment for women with surgically resected early breast cancer that is hormone receptor-positive (HR+), typically defined by breast tumors that express the estrogen receptor (ER), the progesterone receptor (PgR), or both. TAM can have both estrogen-antagonistic and estrogen-agonistic effects, and expression of growth factor receptors such as human epidermal growth factor receptor (HER)2 in breast cancer is associated with the development of TAM resistance. Studies also suggest that a lack of PgR expression in tumors with positive ER status may be associated with increased growth factor expression, a more aggressive tumor phenotype, and TAM resistance. The aromatase inhibitors (AIs) anastrozole, letrozole, and exemestane have proven more effective than TAM as adjuvant hormonal therapy in postmenopausal women with HR+ disease. Some translational studies have also begun to investigate the efficacy of hormonal therapy according to PgR or HER2 status of the tumor. The AIs have proven to be an attractive option for patients across a broad spectrum of receptor expression profiles, and the potential for combination therapy using AIs and specific growth factor inhibitors is also under investigation.

The potential role of sunitinib in gastrointestinal cancers other than GIST - Corrected Proof

Cristina Grávalos, Enrique Grande, Joan Manel Gasent — 2010-02-04

Abstract: Gastrointestinal tumors are the most frequent and lethal malignancies worldwide. The deeper knowledge in molecular biology mechanisms involved in carcinogenesis has allowed the design of new targeted drugs mainly directed against the epidermal growth factor receptor (EGFR), the vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). Sunitinib is an oral multitargeted inhibitor of the VEGF, platelet-derived growth factor (PDGF), and c-KIT, among others, tyrosine kinase receptors. Therefore, sunitinib acts in a dual mode as antiangiogenic agent and as antitumoral drug. The aim of this review is to gather the preclinical rationale behind the clinical use of sunitinib in gastrointestinal malignancies other than gastrointestinal stromal tumors (GIST) and to summarize the clinical data from phase I to III trials currently available.

Employment and work-related issues in cancer survivors - Corrected Proof

Anja Mehnert — 2010-02-01

Abstract: Purpose of this systematic literature review was to identify current knowledge about employment in cancer survivors. Sixty-four studies met inclusion criteria that were original papers published between 01/2000 and 11/2009. Overall, 63.5% of cancer survivors (range 24–94%) returned to work. The mean duration of absence from work was 151 days. Factors significantly associated with a greater likelihood of being employed or return to work were perceived employer accommodation, flexible working arrangements, counseling, training and rehabilitation services, younger age and cancer sites of younger individuals, higher levels of education, male gender, less physical symptoms, lower length of sick leave and continuity of care. Cancer survivors had a significantly increased risk for unemployment, early retirement and were less likely to be re-employed. Between 26% and 53% of cancer survivors lost their job or quit working over a 72-month period post diagnosis. Between 23% and 75% of patients who lost their job were re-employed. A high proportion of patients experienced at least temporary changes in work schedules, work hours, wages and a decline in work ability compared to non-cancer groups.

How has proteomics informed transfusion biology so far? - Corrected Proof

Giancarlo Liumbruno, Angelo D’Alessandro, Giuliano Grazzini, Lello Zolla — 2010-02-01

Abstract: Since the genomic era has not fully kept its promises, studies addressing the protein complement to the genome have been recently gaining momentum. Proteomics investigations could be potentially used from bench to bedside, in order to test the quality of collected blood components prior to or during storage. In parallel, proteomics could be used to verify the effects of the production and pathogen reduction processes of plasma derivatives and blood components on the protein fractions, or to reduce the effects of storage lesions. Another area of interest is represented by the discovery of peculiar biomarkers readily adoptable for targeted evaluation of blood-component integrity or functionality, as well as to assess the proliferative capacity of hematopoietic stem/progenitor cells. These accumulating basic research evidences will hopefully be accompanied by actual applications in routine clinical practice. Whether the costs of the needed facilities (instruments and trained personnel) will meet the current demand of the clinical market, proteomic-expert transfusionists will no longer only inform, but also perform a role in clinical routine.

A mini geriatric assessment helps treatment decision in elderly patients with digestive cancer. A pilot study - Corrected Proof

2010-01-29

Abstract: Comprehensive geriatric assessment (CGA) is advocate to improved care of elderly with cancer but is not available in every hospital within a short delay. Therefore, a tool allowing gastroenterologist to detect rapidly specific abnormalities in elderly is needed.Patients and methods: The aim of our pilot study was to evaluate feasibility of a mini geriatric assessment (MGA) to adapt the anticancer treatments. MGA was done by a gastroenterologist and was taken into account during the cancer multidisciplinary team meeting for making decision. Then, CGA was realised and suggested adaptation of care.Results: 21 patients over 75 years treated for different digestive cancers were enrolled. The treatments recommended by the cancer multidisciplinary team meeting after the GMA were: standard treatments in 9 (41%); modified in 10 (47%) and best supportive care in 2 (12%) patients. CGA led to an adaptation of the non-oncological treatment in 15 (72%) and of the social care in 8 (38%) patients, but never modified the oncological strategy.Conclusions: MGA could help gastroenterologists for adaptation of anticancer treatment. The characteristics of the patients that should subsequently have a geriatric follow-up remain to be defined.

The influences of age and co-morbidities on treatment decisions for patients with HER2-positive early breast cancer - Corrected Proof

Alistair Ring — 2010-01-25

Abstract: Objective: To investigate the influences of age and co-morbidities on the use of adjuvant chemotherapy and trastuzumab in patients with HER2-positive early breast cancer.Methods: Thirty surgeons and 101 oncologists reviewed the profiles of 16 hypothetical patients which included details of age, tumour size/grade, nodal/ER status, and co-morbidities. Respondents viewed different patient profiles. Oncologists were asked how likely they would be to prescribe chemotherapy ±trastuzumab. Surgeons were asked whether they would refer to an oncologist.Results: Oncologists’ treatment decisions were most affected by age and co-morbidities: 81% would prescribe chemotherapy for a high-risk patient aged 68 years, but only 47% for an otherwise identical patient aged 73 years. The majority of surgeons (84%) would still refer older patients.Conclusions: National variation in the use of adjuvant chemotherapy in women aged ≥70 years with high-risk breast cancer is substantial. Practice audits or clinical trials addressing the outcomes of systemic adjuvant therapy are needed for this ever-increasing population of patients.

Diagnosis, evaluation and treatment of carcinoma in situ of the urinary bladder: The state of the art - Corrected Proof

2010-01-25

Abstract: Urothelial carcinoma in situ (CIS) is regarded as a precursor of invasive bladder carcinoma. Although relatively uncommon as a primary entity, CIS is frequently seen in conjunction with other bladder tumors and represents a significant source of difficulty for surveillance of patients with known bladder cancer. CIS lesions are difficult to detect by cystoscopic examination or by currently available screening markers. Urothelial CIS is infrequently reported in the literature as a primary process; however, a wide variety of emerging methodologies are becoming available for screening and follow-up of bladder cancer. Most new methods demonstrate sensitivity and specificity similar to the current standard of urine cytology and cystoscopy. Detection of high-grade lesions such as CIS by these methods appears generally better than detection of low-grade lesions. Current molecular evidence suggests that a spectrum of genetic aberrations including p53 mutations are strongly associated with the potentially invasive CIS phenotype in contrast to low-grade papillary and hyperplastic lesions. These low-grade lesions frequently recur but infrequently become invasive. Patients with high-grade lesions including CIS and high-grade papillary tumors warrant aggressive treatment and life-long surveillance.

First-line chemotherapy with or without biologic agents for metastatic breast cancer - Corrected Proof

Claudia Andreetta, Alessandro M. Minisini, Manuela Miscoria, Fabio Puglisi — 2010-01-25

Abstract: Breast cancer (BC) is one of the most important causes of morbidity and mortality representing the first tumor in the female sex in terms of incidence and the third in terms of mortality in the western world. An increased survival is evident in metastatic breast cancer (MBC) as a result of the introduction of novel therapeutic agents. Oncologists have several options available (chemotherapy, hormone-therapy and biologic agents such as anti-angiogenic and anti-HER2 drugs) and the challenge nowadays is the individualization of the therapy (tailored approach). Despite better diagnostic tools and new therapeutic agents, at the present the main treatment goal in MBC is still palliation.Into the attempt to better tailor treatments, the search for predictive factors deserves a huge effort. This review faces the different approaches in terms of first-line chemotherapy for MBC together with the biological therapies recently approved for the treatment of this tumor.

Identifying an accurate pre-screening tool in geriatric oncology - Corrected Proof

2010-01-08

Abstract: The use of comprehensive geriatric assessment (CGA) in cancer patients older than 70 is recommended. Three pre-screening instruments have been proposed: the abbreviated comprehensive geriatric assessment (aCGA), the Vulnerable Elders Survey (VES-13), and the Groningen frailty index (GFI). The objective of the study was to identify the most efficient pre-screening tool that accurately determines individuals who may benefit from the entire CGA. A total of 113 elderly cancer patients were assessed by means of the aCGA, VES-13, GFI and the full CGA. The sensitivity, specificity of the three instruments was calculated, using the results from the entire CGA as the gold standard for the GFI and the VES-13. The aCGA was assessed whether each sub-component reliably predicts impairment on each sub-component of the full CGA.The majority of the participants were defined as being at risk of vulnerability: 68.14% had two or more impairments of the CGA or were cognitively impaired. The physical and disability questions are useful, but all other screening instruments miss too many cases.

Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer - Corrected Proof

David J. Stewart — 2010-01-04

Abstract: While chemotherapy provides useful palliation, advanced lung cancer remains incurable since those tumors that are initially sensitive to therapy rapidly develop acquired resistance. Resistance may arise from impaired drug delivery, extracellular factors, decreased drug uptake into tumor cells, increased drug efflux, drug inactivation by detoxifying factors, decreased drug activation or binding to target, altered target, increased damage repair, tolerance of damage, decreased proapoptotic factors, increased antiapoptotic factors, or altered cell cycling or transcription factors. Factors for which there is now substantial clinical evidence of a link to small cell lung cancer (SCLC) resistance to chemotherapy include MRP (for platinum-based combination chemotherapy) and MDR1/P-gp (for non-platinum agents). SPECT MIBI and Tc-TF scanning appears to predict chemotherapy benefit in SCLC. In non-small cell lung cancer (NSCLC), the strongest clinical evidence is for taxane resistance with elevated expression or mutation of class III β-tubulin (and possibly α tubulin), platinum resistance and expression of ERCC1 or BCRP, gemcitabine resistance and RRM1 expression, and resistance to several agents and COX-2 expression (although COX-2 inhibitors have had minimal impact on drug efficacy clinically). Tumors expressing high BRCA1 may have increased resistance to platinums but increased sensitivity to taxanes. Limited early clinical data suggest that chemotherapy resistance in NSCLC may also be increased with decreased expression of cyclin B1 or of Eg5, or with increased expression of ICAM, matrilysin, osteopontin, DDH, survivin, PCDGF, caveolin-1, p21WAF1/CIP1, or 14-3-3sigma, and that IGF-1R inhibitors may increase efficacy of chemotherapy, particularly in squamous cell carcinomas. Equivocal data (with some positive studies but other negative studies) suggest that NSCLC tumors with some EGFR mutations may have increased sensitivity to chemotherapy, while K-ras mutations and expression of GST-pi, RB or p27kip1 may possibly confer resistance. While limited clinical data suggest that p53 mutations are associated with resistance to platinum-based therapies in NSCLC, data on p53 IHC positivity are equivocal. To date, resistance-modulating strategies have generally not proven clinically useful in lung cancer, although small randomized trials suggest a modest benefit of verapamil and related agents in NSCLC.

Abnormal immunity and stem/progenitor cells in acquired aplastic anemia - Corrected Proof

Jian Ping Li, Cui Ling Zheng, Zhong Chao Han — 2010-01-04

Abstract: Acquired aplastic anemia (AA) is considered as an immune-mediated bone marrow failure syndrome, characterized by hypoplasia and pancytopenia with fatty bone marrow. Abnormal immunity is the major factor mediating the pathogenesis of acquired AA. Activated DCs might promote the polarization to Th1 cells, and activate CD8+ T cells. A variety of immune molecules including IFN-γ, TNF-α, MIP-1α and IL-2, 8, 12, 15, 17, 23, produced by them and stromal cells, compose a cytokine network to destruct stem/progenitor cells as well as hematopoietic stem/progenitor cells, mesenchymal stem cells (MSCs) and angioblasts/endothelial progenitor cells. Inversely, deficient MSCs, CD4+CD25+ T cells, NK cells, NKT cells and early hematopoietic growth factors diminish the capacity of immune regulation and the support of hematopoiesis. As a result, stem/progenitor cells are significantly impaired to be disabled cells with markedly deficient proliferation, differentiation, induced apoptosis and dysfunctional response to growth factor stimuli, together with rare normal ones. Although some patients can be ameliorated by stem-cell transplantation or immunosuppressive therapy, more effective and convenient therapies such as patient-specific pluripotent iPS cells based on definite pathogenesis are expected.

Preoperative radiochemotherapy for resectable localised oesophageal cancer: A controversial strategy - Corrected Proof

2009-12-31

Abstract: Preoperative chemoradiation (P-CRT) remains a controversial strategy in the treatment of squamous cell cancer (SCC) and adenocarcinoma (ADC) of the oesophagus. Until recently, randomised studies mixed the two, often without any distinction. In randomised studies involving exclusively SCC, P-CRT increases the rate of local control, R0 resection, pCR and disease-free survival. The absence of any impact on overall survival may be linked to the toxic effects of this treatment. Meta-analyses have revealed a survival benefit of approximately +13% at 2 years. However, the methodology used was perhaps questionable. Five randomised trials involving ADC patients compared P-CRT with surgery alone. The results were contradictory with insufficient statistical power in selected positive studies to answer this issue once and for all. P-CRT is unsatisfactory as a standard treatment. Although local control rates were increased with P-CRT, it should be considered only for selected patients in selected centres.

First-line single-agent cetuximab in elderly patients with metastatic colorectal cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD) - Corrected Proof

2009-12-30

Abstract: Purpose: To evaluate the efficacy and safety of first-line single-agent cetuximab in fit elderly patients with metastatic colorectal cancer, as well as potential molecular predictive factors for efficacy.Patients and methods: Patients aged 70 or older with metastatic CRC without criteria for frailty and no prior treatment for advanced disease were treated with single-agent cetuximab 400mg/m2 followed by weekly 250mg/m2 until disease progression or unacceptable toxicity.Results: Forty-one patients were included. Two patients achieved a complete response and 4 patients had a partial response for an overall response rate of 14.6%. Fifteen patients (36.6%) remained stable. Median time to progression was 2.9 months and median overall survival 11.1 months despite two-third of patients received chemotherapy at progression. Forty-five percent of EGFR gene copy number positive patients by FISH were progression-free at 12 weeks, in contrast with 12% of FISH negative patients (p=0.04). Grade 3 skin toxicity was reported in 5 patients (12.2%). Hypersensitivity infusion reactions were not reported and there were no toxic deaths.Conclusion: Cetuximab is a safe monoclonal antibody with moderate activity in first-line metastatic colorectal cancer, but the present study does not support the use of cetuximab as single-agent in first-line fit elderly patients with metastatic CRC.

Cancer patients with cardiovascular disease have survival rates comparable to cancer patients within the age-cohort of 10 years older without cardiovascular morbidity - Corrected Proof

2009-12-28

Abstract: Due to aging of the population the prevalence of both cardiovascular diseases (CVDs) and cancer is increasing. Elderly patients are often under-represented in clinical trials, resulting in limited guidance about treatment and outcome. This study gives insight into the prevalence of CVD among unselected patients with colon, rectum, lung, breast and prostate cancer and its effects on cancer treatment and outcome. Over one fourth (N=11,200) of all included cancer patients aged 50 or older (N=41,126) also suffered from CVD, especially those with lung (34%) or colon cancer (30%). These patients were often treated less aggressively, especially in case COPD or diabetes was also present. CVD had an independent prognostic effect among patients with colon, rectum and prostate cancer. This prognostic effect could not be fully explained by differences in treatment.Conclusions: Many cancer patients with severe CVD have a poorer prognosis. More research is needed for explaining the underlying factors for the decreased survival. Such research should lead to treatment guidelines for these patients.

Angioprevention with fenretinide: Targeting angiogenesis in prevention and therapeutic strategies - Corrected Proof

2009-12-25

Abstract: Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR; fenretinide), a synthetic retinoic acid derivative, is a highly active and promising therapeutic and chemopreventive agent. Fenretinide shows biological activity against numerous cancer types in vitro and in preclinical studies. Clinical trials have shown that fenretinide induces a significant reduction of second breast cancer in premenopausal women. Several studies on different neoplasms are ongoing, such as breast and ovarian cancer, neuroblastoma, glioblastoma, head and neck and skin cancers and others. It has minimal side effects in humans, so that trials in young women at high-risk of breast cancer and ovarian and for the prevention of other tumor types such as lung cancer could be envisaged. Here we review some ongoing clinical trials and evaluate the possible mechanisms underlying the secondary chemopreventive effects of 4HPR. In particular we report basic and translational data on the anti-angiogenic “angiopreventive” properties of fenretinide, its anti-invasive activity, its ability to induce apoptosis and to generate or enhance production of reactive oxygen species as possible molecular bases for a chemopreventive action in patients.

Cognitive functioning of postmenopausal breast cancer patients before adjuvant systemic therapy, and its association with medical and psychological factors - Corrected Proof

2009-12-25

Abstract: Purpose: This study aimed to identify medical and psychological predictors for cognitive performance of breast cancer (BC) patients before the start of adjuvant systemic treatment and to compare cognitive performance between BC patients and healthy controls adjusting for medical and psychological variables.Material: 205 postmenopausal BC patients underwent pre-treatment neuropsychological tests and provided medical and psychological data. 124 healthy controls underwent the same assessment.Results: ‘Treatment for diabetes mellitus’ and/or ‘hypertension’, ‘less hours spent on cognitively stimulating activities’, ‘fewer days since surgery’ and ‘more reproductive years’ were associated with worse cognitive performance in the BC patients, independent of age and IQ. Cognitive differences between BC patients and healthy controls could partly be explained by the evaluated variables.Conclusion: The results stress the need for adjustment for pre-treatment cognitive differences between study groups, and also indicate that further research into pre-treatment cognitive dysfunction is warranted.

Comprehensive geriatric assessment can predict complications in elderly patients after elective surgery for colorectal cancer: A prospective observational cohort study - Corrected Proof

2009-12-14

Abstract: Objective: To examine the association between the outcomes of a pre-operative comprehensive geriatric assessment (CGA) and the risk of severe post-operative complications in elderly patients electively operated for colorectal cancer.Methods: One hundred seventy-eight consecutive patients ≥70 years electively operated for all stages of colorectal cancer were prospectively examined. A pre-operative CGA was performed, and patients were categorized as fit, intermediate, or frail. The main outcome measure was severe complications within 30 days of surgery.Results: Twenty-one patients (12%) were categorized as fit, 81 (46%) as intermediate, and 76 (43%) as frail. Eighty-three patients experienced severe complications, including three deaths; 7/21 (33%) of fit patients, 29/81 (36%) of intermediate patients and 47/76 (62%) of frail patients (p=0.002). Increasing age and ASA classification were not associated with complications in this series.Conclusion: CGA can identify frail patients who have a significantly increased risk of severe complications after elective surgery for colorectal cancer.

Brain metastases in HER2-positive breast cancer: The evolving role of lapatinib - Corrected Proof

2009-12-10

Abstract: Due to improvements in diagnosis and systemic therapy, brain metastases are an increasingly common cause of morbidity and mortality for patients with advanced breast cancer. The incidence of symptomatic brain metastases among women with metastatic breast cancer ranges from 10% to 16%. The HER2 receptor, which is overexpressed in approximately 25% of all breast cancers, is an important risk factor for the development of central nervous system metastases. Surgery and radiation therapy are the primary approaches to the treatment of brain metastases but new chemotherapy and biological agents promise to play an important role in the future management of central nervous system disease. This article reviews the epidemiology, current treatment options and recent advances in the field, with a focus on HER2-positive disease and the emerging role of lapatinib for the treatment and prevention of brain metastases.

Tumour markers predictive of successful treatment of breast cancer with primary endocrine therapy in patients over 70 years old: A prospective study - Corrected Proof

Anne Stotter, Rosemary Walker — 2009-12-07

Abstract: We report a prospective study of women over 70 years of age with early breast cancer who had primary endocrine treatment. Core biopsies of the cancer were taken at diagnosis and assessed using immunohistochemistry for oestrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor (EGFR), pS2, cyclin D1, p21, p53, HER2 and MIB1 (Ki67). Outcome analysis was performed at a median follow-up of 70 months. Correlation was sought between tumour marker measurements and disease control. When all patients were considered, a significant relationship was found between the absence of ER and PgR, the presence of p53 and EGFR, and high MIB1 and treatment failure. However, for the ER positive cancers, no other marker predicted treatment failure or relapse. There remains an important clinical need to identify those ER positive breast cancers that will not respond to endocrine treatment, and those in which the response will be short-lived.

Major and minor salivary gland tumors - Corrected Proof

2009-11-26

Abstract: Malignant salivary gland tumors are rare. The most common tumor site is the parotid. Aetiologic factors are not clear. Nutrition may be a risk factor, as well as irradiation or a long-standing histologically benign tumor that occurs at youth. Painless swelling of a salivary gland should always be considered as suspicious, especially if no sign of inflammation is present. Signs and symptoms related to major salivary gland tumors differ from those concerning minor salivary gland tumors, as they depend on the different location of the salivary gland. Surgical excision represents the standard option in the treatment of resectable tumors of both major and minor salivary glands. Neutron, heavy ions or proton radiotherapy may be a treatment option for inoperable locoregional disease. Surgery, irradiation or re-irradiation are treatment options for local relapse, whereas radical neck dissection is indicated for regional relapses. Metastatic disease may be either treated with radiotherapy or palliative chemotherapy, depending on the site of metastases. For highly selected patients the employment of anti-androgen therapy is indicated.

Impact of comorbidities on clinical outcomes in non-small cell lung cancer patients who are elderly and/or have poor performance status - Corrected Proof

2009-11-26

Abstract: Aim: We evaluated the effect of comorbidities on clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) who have poor performance status (PS 2/3) and/or are elderly (≥70 years old).Summarized description: The impact of age (<70 versus >70), PS, and comorbidity score - Cumulative Illness Rating Scale for Geriatrics (CIRS-G) on treatment response, toxicities, QOL and overall survival (OS) was analyzed using data from a completed phase II trial that randomly assigned patients with advanced NSCLC who had PS 2/3 and/or were aged ≥70 to receive gemcitabine (GEM), vinorelbine (VIN) or docetaxel (DOC).Results: Data from records of 134 patients accrued during the trial were available for analysis. Eighty-eight patients (66%) were aged ≥70 years. 59 patients (67%) had PS of ECOG 0–2 and 29 patients (33%) had ECOG 3. In those aged ≥70, 53 (60%) had at least one comorbidity rated CIRS-G category 3/4 while those aged <70, 12 (26%) had at least one CIRS-G 3/4 comorbidity. Age, PS, and comorbidity scores had no significant association with PFS and QOL scores changes, although PS had marginal influence on OS (0.05

Does frailty predict hospitalization, emergency department visits, and visits to the general practitioner in older newly-diagnosed cancer patients? Results of a prospective pilot study - Corrected Proof

M.T.E. Puts, J. Monette, V. Girre, C. Wolfson, M. Monette, G. Batist, H. Bergman — 2009-11-26

Abstract: Research on the use of health care by older newly-diagnosed cancer patients is sparse. We investigated whether frailty predicts hospitalization, emergency department (ED) and general practitioner (GP) visits in older cancer patients in a prospective pilot study. Newly-diagnosed cancer patients aged 65 years and over were recruited in the Segal Cancer Centre, Jewish General Hospital, Montreal, Canada. One hundred ten patients participated, mean age 74.1, 70% women. During 1 year follow-up, 52 patients (47.3%) had cancer-related hospitalizations, 23 patients (20.9%) had ED visit and 17 patients (15.5%) had GP visit. No frailty marker predicted hospitalization or visits to the GP. Cognitive impairment suspicion was the only frailty marker that predicted ED visits (odds ratio 4.97; 95%CI 1.14–21.69). Although health care use was considerable in this sample, most frailty markers were not associated with health care use in this pilot study.

Histopathologic and genetic alterations as predictors of response to treatment and survival in lung cancer: A review of published data - Corrected Proof

2009-11-16

Abstract: Lung carcinogenesis is considered to be the result of composite environmental, genetic and epigenetic changes. Despite the fact that many of the genetic alterations, including loss of heterozygocity in the 3p chromosome locus and point mutations in the tumor-suppressor genes TP53 and retinoblastoma (RB1), occur in nearly all histopathologic types of lung cancer, the frequency and the “timing” of their occurrence seems to differ between small-cell lung cancer (SCLC) cells, that are characterized by neuroendocrine differentiation, and non-small-cell lung cancer (NSCLC) cells. Although loss of cell-cycle control is the crucial molecular event in both types, the mechanism by which it provokes oncogenesis differs significantly between SCLC and NSCLC. Importantly, some of these molecular events, including DNA-damage response and epidermal growth factor receptor (EGFR) mutations are valuable in predicting response to conventional chemotherapy or molecular-targeted agents as well as in the prognosis of patients that harbor these alterations. In the current review we report on the best characterized histopathologic and genetic changes in NSCLC and SCLC in relation to each histological subtype and we discuss their predictive and prognostic implications.

Serous papillary peritoneal carcinoma: Unknown primary tumour, ovarian cancer counterpart or a distinct entity? A systematic review - Corrected Proof

George Pentheroudakis, Nicholas Pavlidis — 2009-11-09

Abstract: Introduction: Serous peritoneal papillary carcinoma (SPPC), though managed according to ovarian cancer therapeutic principles, has been variably considered as an ovarian cancer counterpart, a peritoneal malignancy with distinct characteristics or a cancer of unknown primary (CUP).Patients and methods: We systematically reviewed all publications studying molecular pathophysiology, clinical presentation, management and outcome of at least 10 patients with SPPC from 1980 to 2008 in anglophone medical journals and critically analysed the data.Results: Molecular profiling of CUP was performed in eight papers reporting on 211 patients with stage III/IV SPPC by means of immunohistochemistry or PCR-based assays. Twenty-five clinical series, mostly retrospetive, reported management and outcome of 579 patiens with SPPC, in several cases matched to advanced ovarian cancer controls. Though we did not identify statistically significant differences in molecular biology, clinical presentation, management and outcome of SPPC and ovarian cancer cases, some subtle differences emerged: patterns of loss of heterozygosity at several chromosomal loci differed from those seen in ovarian cancer, while the overexpression of the HER2 oncogene was encountered more often. Serous peritoneal tumours affected older patients and were more frequently multifocal or exhibited virulent clonal expansion in metastatic sites. Diffuse micronodular spread formed a high total load of malignancy in omental, peritoneal surfaces, difficult to debulk optimally. Despite effective chemotherapeutic cytoreduction and occasional long-term remissions, SPPC patients survived 2–6 months less than ovarian cancer patients.Conclusions: Patients with SPPC should not be classified in the poor-risk CUP category, in view of the therapeutic and prognostic differences. Still, the assimilation of the SPPC entity by ovarian cancer hindered further research into its genotypic and phenotypic characteristics that may differ from ovarian cancer. Subgroup analyses of large ovarian cancer trials may shed light in this issue.

Prescribers’ attitudes toward elderly breast cancer patients. Discrimination or empathy? - Corrected Proof

Christel Protière, Patrice Viens, Frédérique Rousseau, Jean Paul Moatti — 2009-10-26

Abstract: Advancing age is often associated with co-morbidities. Patients’ chronological and physiological ages do not always correspond. Elderly patients are often excluded from clinical trials and given sub-optimum treatment. In this context, the question of equity in access to health care arises.A specially designed questionnaire was mailed to French oncologists to determine what factors influenced them and to elicit their medical practice using four clinical cases.Significant differences in treatment choice depending only on patient's age were observed. The likelihood of an elderly breast cancer patient undergoing chemotherapy was found to depend on physician specialty and gender, kind of care structure, physician's perception of the age at which patients become elderly, and their knowledge about geriatric assessments. Some physicians did not always prescribe potentially beneficial treatments when dealing with elderly patients. Given the multidimensional nature of the care process, patients’ preferences should be taken into account in medical decision-making.

Optimizing the management of metastatic colorectal cancer - Corrected Proof

Pasquale Comella, Rossana Casaretti, Antonio Avallone, Luca Franco — 2009-10-19

Abstract: The prognosis of patients with metastatic colorectal cancer has significantly improved in the last few years, with the introduction into the clinical practice of new cytotoxic treatments, the availability of non-cross resistant agents after the front-line treatment failure, and the combination of targeted agents (i.e., the inhibitors of the epidermal growth factor and vascular endothelial growth factor pathways) with conventional drugs. All these options must be incorporated into a complex strategy of management, in which a customized management according to the disease status, with an intensified induction approach followed by maintenance (and reinduction), should be investigated.

Primary cutaneous marginal zone lymphoma - Corrected Proof

2009-10-12

Abstract: Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is included in the group of extranodal marginal zone B-cell lymphoma involving mucosal sites. Many evidences suggest that chronic antigen stimulation is a key-player in its pathogenesis. While Helicobacter pylori seems not to be implicated in PCMZL, Borrelia Burgdorferi's role is still matter of debate since the results are discordant between European and North American/Asian countries. However Borrelia subspecies are different between the studied areas and this difference could be a confounding factor. Then ubiquitous candidate antigen is still missing. Beyond these discrepancies the treatment of diffuse PCMZL has been recently improved. If local therapies (surgery, radiation) are the gold standard for localized disease, rituximab can also be considered as an alternative for disseminated or plurifocal PCMZL.

Variation in breast cancer subtypes with age and race/ethnicity - Corrected Proof

Carol A. Parise, Katrina R. Bauer, Vincent Caggiano — 2009-10-05

Abstract: Background: Both age and race have been identified as independent predictors of breast cancer subtype but the association of age with subtype within each race is not well understood. This study assesses the association of age with the eight breast cancer subtypes as defined by ER/PR/HER2 among white, African-American, Hispanic, and Asian/Pacific Islander women.Methods: This study included 69,358 women with primary invasive breast cancer. Logistic regression was used to assess the association of age with each of the ER/PR/HER2 subtypes for each race adjusted for socioeconomic status, stage, grade, and tumor size.Results: The odds of African-American women having a triple-negative tumor were not statistically significantly increased for women under 46 when compared to the African-American women aged 46–69 (OR=0.96; 95% CI=0.80–1.16). A similar pattern was observed for the ER−/PR−/HER2+ subtype. Hispanic women under age 46 (OR=0.83; 95% CI=0.71–0.97) and over age 70 (OR=0.71; 95% CI=0.57–0.89) were less likely to have the ER−/PR−/HER2+ subtype. Asian/Pacific Islander women under age 46 also had reduced odds (OR=0.67; 95% CI=0.55–0.82) of the ER−/PR−/HER2+ subtype.Conclusions: The ER/PR/HER2 subtypes vary with age and differences in this variation depend on race. It is important to define breast cancer using the ER/PR/HER2 subtype and the significance of age and race should not be overlooked.

Treatment for metastatic malignant melanoma: Old drugs and new strategies - Corrected Proof

2009-09-25

Abstract: The number of melanoma cases worldwide is increasing faster than any other cancer and remains one of the most treatment-refractory malignancies. Despite decades of clinical trials testing chemotherapy and immunotherapy, a standard first-line treatment for metastatic melanoma has not yet been established; tough single agent dacarbazine represents the most common option. This review will focus on metastatic malignant melanoma treatment from single agent until new therapies. An overview of established chemotherapies and immunotherapies, followed by a summary of trials testing the potential combination and new agent are explored.

Review role of topotecan in gynaecological cancers: Current indications and perspectives - Corrected Proof

2009-09-22

Abstract: Background: Ovarian cancer is the fourth cause of death from gynaecological cancer and cervical cancer is the first in women <45 years old in developing countries.The aim of this article is to review the role of topotecan (Hycamtin®), a semi-synthetic alkaloid derivative of camptothecin, in ovarian and cervical cancer in monotherapy and in combination.Methods: This article reviews the mechanism of action, pharmacokinetics, toxicity and efficacy of topotecan. The paper also reports the principal phases II and III studies of topotecan in advanced or recurrent ovarian and cervical cancer.Results: Topotecan (Hycamtin®), currently indicated for the treatment of relapsed ovarian cancer, has demonstrated activity both in platinum-sensitive and in platinum-resistant disease. The combination cisplatin–topotecan for the treatment of advanced and recurrent cervical cancer has demonstrated a clinical benefit in terms of response rate, overall survival and progression free survival. Haematological toxicity of topotecan also is easy to manage and not cumulative, especially with the weekly scheduled recently introduced in clinical practice.Conclusion: Topotecan (Hycamtin®) will continue to play a role in the treatment of advanced ovarian and cervical cancer, in monotherapy or in combination with other cytotoxic agents.

Pegfilgrastim primary prophylaxis vs. current practice neutropenia management in elderly breast cancer patients receiving chemotherapy - Corrected Proof

2009-09-14

Abstract: We investigated the incidences of febrile neutropenia (FN) and related complications in elderly (≥65 years) breast cancer patients receiving chemotherapy supported by pegfilgrastim primary prophylaxis (PP; n=150) or current practice (CP) neutropenia management (n=104) in a subanalysis of NeuCuP (Neulasta® vs. current practice neutropenia management). Studies involving regimens with moderately high to high (≥15%) FN risk were identified by literature review, and individual patient data were integrated for analysis. FN incidence was 6% (95% CI: 2, 10%) in the PP group and 24% (95% CI: 16, 32%) in the CP group. In cycle 1, incidences were 3 and 15%, respectively. FN-related hospitalisation incidence was 5% (PP group) and 15% (CP group), while dose reductions (≥15%) occurred in 15 and 29% of patients. Pegfilgrastim provided effective PP in elderly patients, a population who may be vulnerable to chemotherapy-related FN and for whom current practice may not provide adequate protection.

Clinical outcome of elderly patients with metastatic colorectal cancer treated with FOLFOXIRI versus FOLFIRI: Subgroup analysis of a randomized phase III trial from the Hellenic Oncology Research Group (HORG) - Corrected Proof

2009-09-04

Abstract: Background: A subgroup analysis of oxaliplatin (LOHP)+irinotecan (CPT-11)+5-fluorouracil (5FU) and leucovorin (LV) (FOLFOXIRI regimen) versus irinotecan+5FU/LV (FOLFIRI regimen) as first-line treatment of patients >65 years old with metastatic colorectal cancer is presented.Patients and Methods: Eighty-two (56%) and 75 (55%) patients with metastatic colorectal cancer aged >65 years were enrolled in the FOLFOXIRI and FOLFIRI regimen, respectively.Results: There was no statistically statistical difference in terms of overall survival or time-to-tumor progression between young and aged patients between the two chemotherapy arms. The objective response rate was significantly lower in older patients treated with FOLFOXIRI (32% vs. 52%; OR: 1.45, 95% CI: 1.06–2.09; p=0.03). Elderly patients experienced a significantly higher incidence of grade 3/4 diarrhea compared to younger patients, irrespectively of the chemotherapy regimen (p=0.005 for FOLFIRI; p=0.017 for FOLFOXIRI). Dose reductions and treatment delays were more frequent in the FOLFOXIRI arm.Conclusion: FOLFOXIRI does not seem to offer substantial benefit compared to FOLFIRI regimen in elderly patients with metastatic colorectal cancer.

Cancer in nonagenarians: Profile, treatments and outcomes - Corrected Proof

Martine Extermann, Edward J. Crane, David Boulware — 2009-09-01

Abstract: An increasing number of nonagenarians are treated for cancer. However, very few data are available to guide treatment choices in this often frail population. The charts of all patients registered at Moffitt Cancer Center between 1993 and 2006 who were aged 90 or older at the time of treatment/evaluation were reviewed, and those treated for an active cancer (n=177) were included in the analysis. For 23.5% of patients, the index cancer was a second malignancy. Initial treatments were: surgery 41%, chemotherapy 9%, radiation therapy 15%, concomitant chemo-radiation therapy 2%, hormonal therapy 12%, targeted therapy 8%, photodynamic therapy 1%, observation/supportive care 3%, hospice 9%. The median survival was 1.69 years [95% CI=1.34, 2.17, range 0.1–6.21]. For early stage cancer it was 2.02 years [95% CI=1.56, 2.87], and for advanced stage cancer, 1.06 years [95% CI=0.58, 1.63] (p=0.02 by log-rank). Treatment related mortality was low (1.1%). In conclusion, our nonagenarians underwent a broad range of treatments with low treatment related mortality. Advanced cancer still limits the survival of nonagenarians. Second cancers are frequent in older cancer survivors.

Patterns of care and survival in cancer patients with cognitive impairment - Corrected Proof

Claire Robb, David Boulware, Janine Overcash, Martine Extermann — 2009-08-27

Abstract: To address the emerging concern of oncologists who can expect to see an increasing number of older cancer patients with dementia, this retrospective case–control study compared a sample of older cancer patients with cognitive impairment (N=86) to a non-cognitively impaired control group (N=172) as to patterns of care and survival by age, site and stage. Treatment patterns presented much less differences between both groups than in other series. After adjusting for age, sex, performance status, ADLs/IADLs and comorbidity, results showed significantly greater survival (values p<.001) in the non-impaired control group (Mdn=72.6 months) compared to the cognitively impaired cases (Mdn=23.0 months). Similar results were found when we compared these groups according to tumor stage and cancer site (breast versus other). Across tumor types and stages, cognitively impaired patients have approximately one-third the median survival of the control group. This survival can still be a significant number of years.

Improving disease control in advanced colorectal cancer: Panitumumab and cetuximab - Corrected Proof

2009-08-25

Abstract: Colorectal cancer remains a major public health concern in Europe and North America. It is responsible for one million new cases and half a million deaths per year worldwide. During the past few years new effective treatments have evolved improving the outcome of patients with this disease. Several alternatives are currently available for advanced colorectal cancer patients including different chemotherapeutic regimens (fluoropyrimidines, irinotecan and oxaliplatin) and targeted therapies such as bevacizumab and cetuximab. Different combinations achieve a median survival of over 2 years. Intense efforts focus on identifying agents targeting growth factor receptors, signal transduction pathways or angiogenesis mediators. One of the last available drugs for the management of advanced colorectal cancer is panitumumab, a well-tolerated and effective anti-EGFR monoclonal antibody approved as a single agent in chemotherapy refractory patients. We discuss the current evidence supporting panitumumab for metastatic colorectal cancer treatment, potential predictive biomarkers and ongoing clinical trials with different combinations including panitumumab.

Enhancing geriatric oncology training to care for elders: A clinical initiative with long-term follow-up - Corrected Proof

John M. Bennett, William J. Hall, Deepak Sahasrabudhe, Lodovico Balducci — 2009-08-10

Abstract: There is an urgent need to train and foster academic geriatric oncologists (GO) who can participate in a wide number of initiatives designed to confront the increasing burden of an aging population on the health care delivery systems. Over the past decade a new training program to achieve an increase in GO's was established in the United States with the support of the John A. Hartford Foundation and the American Society of Clinical Oncology. In this review we document the scope of the activities, the results and the future of similar programs and the development of successor programs.

Weekly paclitaxel versus weekly docetaxel in elderly or frail patients with metastatic breast carcinoma: A randomized phase-II study of the Belgian Society of Medical Oncology - Corrected Proof

2009-08-03

Abstract: This randomized phase-II trial investigated the efficacy and tolerability of weekly docetaxel or paclitaxel in metastatic breast cancer (MBC) patients considered unfit for a 3-weekly therapy.The primary study endpoint was antitumor activity, the second endpoint was tolerability, time to progression (TTP) and overall survival (OS). In intent-to-treat analysis, we observed for paclitaxel and docetaxel respectively partial response (PR) in 48% versus 38%, stable disease (SD) in 24% versus 16%, PD in 15% versus 30%. Median TTP was 21.1 weeks versus 12.7 weeks and median OS 55.7 weeks versus 32 weeks. Toxicity profiles were acceptable with more anemia and neurotoxicity for paclitaxel and more edema and fatigue for docetaxel.In patients with MBC unfit for 3-weekly docetaxel or paclitaxel, weekly administration of either compound may certainly be considered. They display different, but acceptable toxicity profiles, with levels of antitumoral efficacy comparable to those previously reported for 3-weekly regimens.

Integration of panitumumab into the treatment of colorectal cancer - Corrected Proof

Cristina Gravalos, Javier Cassinello, Pilar García-Alfonso, Antonio Jimeno — 2009-07-21

Abstract: Conventional chemotherapy increases progression-free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) patients versus best supportive care (BSC). However, the efficacy of chemotherapy is limited. Recently approved monoclonal antibodies (MoAb) have a different mechanism of action, targeting growth factors or their receptors.Panitumumab is a fully human IgG2 MoAb directed against the epidermal growth factor receptor (EGFR). In phase II trials, panitumumab showed preliminary activity in chemorefractory mCRC. This efficacy was confirmed in a randomized pivotal phase III trial, which compared single-agent panitumumab plus BSC versus BSC alone. Several ongoing clinical trials are evaluating panitumumab in combination with different chemotherapy regimens in first- and second-line settings. Skin toxicities, hypomagnesemia, and diarrhea are the most common adverse events associated with anti-EGFR therapy. KRAS status and skin rash have been correlated with panitumumab efficacy.This article reviews the preclinical and pharmacokinetics data, activity and tolerance of panitumumab in mCRC patients. Potential predictive factors of response are also discussed.

Associations of social networks with cancer mortality: A meta-analysis - Corrected Proof

Martin Pinquart, Paul R. Duberstein — 2009-07-15

Abstract: This meta-analysis integrates results of 87 studies on the associations of perceived social support, network size, and marital status with cancer survival. In controlled studies, having high levels of perceived social support, larger social network, and being married were associated with decreases in relative risk for mortality of 25%, 20%, and 12%, respectively. Moderator analyses revealed that never married patients had higher mortality rates than widowed and divorced/separated patients. Associations of social network with mortality were stronger in younger patients, and associations of marital status with mortality were stronger in studies with shorter time intervals, and in early-stage cancer. Relationships varied by cancer site, with stronger associations of social support observed in studies of patients with leukemia and lymphomas and stronger associations of network size observed in studies of breast cancer. Further randomized intervention studies are needed to test causal hypotheses about the role of social support and social network for cancer mortality.

The role of immunity in elderly cancer - Corrected Proof

Lucia Malaguarnera, Erika Cristaldi, Mariano Malaguarnera — 2009-07-06

Abstract: The increased incidence of malignancies in elderly patients living in industrialized countries has led to both identify the causes that alter the normal homeostatic balance in elderly and designate the specific treatments. The progressive decline of the immune system (immunosenescence) involving cellular and molecular alterations impact both innate and adaptive immunity. The immunosenescence leads to increased incidence of infectious diseases morbidity and mortality as well as heightened rates of other immune disorders such as autoimmunity, cancer, and inflammatory conditions. Here, we summarize the knowledge on the major changes in the immune system associated with aging in primary lymphoid organs as well as a description of molecular mechanisms, and the impact on cancer development.

Adjuvant chemotherapy in elderly patients with colorectal cancer. A retrospective analysis of the implementation of tumor board recommendations in a single institution - Corrected Proof

2009-06-29

Abstract: Background: A number of studies have shown that elderly cancer patients were denied optimal anticancer treatment because of age. Colorectal cancer is among the most frequent cancers in Western countries, and adjuvant chemotherapy has proven efficacy and tolerance in this condition. This study was undertaken to explore the current approaches to adjuvant chemotherapy in elderly cancer patients in a single institution.Patients and methods: We retrospectively analyzed all patients’ files that were discussed in the gastro-intestinal tumor board of the Hôpitaux Universitaires de Strasbourg during 3 years (2004–2006). The recorded variables included sex, age, tumor stage, cancer location colon vs rectum, number of comorbidities, occurrence of an oncogeriatric assessment, type and tolerance of chemotherapy. We investigated the reason to not administer adjuvant therapy in patients whom should have received this treatment if guidelines had to be applied.Results: A total of 193 consecutive patients’ files were extracted from colorectal cancer patients that had been discussed in the gastro-intestinal tumor board. Among these, we isolated patients over 70 years old who were proposed with either adjuvant chemotherapy (group A, n=65) or follow up (group B, n=128). The median age in group A was 75.3 years old. Tumor board recommendations were in accordance with guidelines in 91% of cases. Chemotherapy was delivered in 44 pts (76%) and completed in 42 (95%). The median age in group B was 78.6 years old, and in this group tumor board proposal met the guidelines in 83% of cases. In the logistic regression model, disease stage was the major variable leading to adjuvant treatment recommendation, age and comorbidities being of lesser importance.Conclusions: In our series, elderly colorectal cancer patients are not undertreated. Efforts should be maintained to educate physicians with regard to feasibility of adjuvant chemotherapy in elderly patients.

Six independent domains are defined by geriatric assessment in elderly cancer patients - Corrected Proof

R. Stauder, K. Moser, B. Holzner, B. Sperner-Unterweger, G. Kemmler — 2009-06-11

Abstract: Background: Geriatric assessment (GA) must be integrated into treatment concepts for elderly cancer patients. Aim of this study was to assess the coverage of a large battery of GA instruments by determining the number of independent domains measured.Methods: Thirteen different GA scores were applied in 78 elderly tumor patients (mean age 72.9 years). Data were analyzed by exploratory factor analysis and substantiated by non-parametric correlation analyses.Results: Factor analysis yielded a six-factor solution explaining 77.1% of the total variance. The six domains identified may be described as general functioning in everyday life, health-related quality of life, co-morbidities, social support, cognition, and nutritional status. This factor structure was reasonably well confirmed by correlation analyses. Notably, WHO Performance Status, Karnofsky Index, VES-13 and PPT generally revealed high correlations with functional capacities, but only low correlations with comorbidities, social support, cognitive functioning or nutritional status.Conclusions: From the six domains described a basis for efficient application of GA instruments in elderly cancer patients is worked out. The classical instruments WHO and KI as well as the screening scores VES-13 and PPT, while capturing physical functioning well, fail to cover several other important GA domains.

MicroRNA and leukemia: Tiny molecule, great function - Corrected Proof

Haifeng Zhao, Donghai Wang, Weiting Du, Dongsheng Gu, Renchi Yang — 2009-06-11

Abstract: MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted messenger RNAs (mRNAs). It is known that aberrant microRNA expression can play a vital role in the pathology of leukemia, thus microRNAs have rapidly emerged as potential targets for therapeutics. This review focuses on recent researches on the important roles of microRNAs in the pathogenesis of leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL).

Lhermitte's sign: Review with special emphasis in oncology practice - Corrected Proof

Cengiz Gemici — 2009-06-03

Abstract: Lhermitte's sign (LS) is characterized by electric shock like sensation, spreading along the spine in a cervico-caudal direction and also into both arms and legs, which is felt upon forward flexion of the neck. It is a myelopathy resulting from damage to sensory axons at the dorsal columns of the cervical or thoracic spinal cord and a well-known clinical sign in neurology practice. Patients with cancer may present with LS due to various causes either related to the tumor itself or to its treatment. Spinal cord tumors, radiotherapy and chemotherapy are possible causes of LS observed in oncology practice. While LS is observed with a frequency of 3.6–13% in large patient groups receiving radiotherapy for head and neck and thoracic malignancies, the true incidence of chemotherapy and spinal cord tumor induced LS is unknown with only few reported cases in the literature. In the present article, various pathologies causing Lhermitte's sign are reviewed with special emphasis on the implications of this sign in oncology practice.

The upgraded role of HER3 and HER4 receptors in breast cancer - Corrected Proof

2009-06-01

Abstract: The human epidermal growth factor receptor (HER) family comprises four homologous members. The activation of these receptors affects essential tumorigenic processes and plays a crucial role in the pathogenesis of breast cancer. Among HER family members, EGFR and HER2 are the most studied. However, accumulating data provide evidence for the significance of HER3 and HER4 alterations in breast carcinogenesis. The combination of HER2 and HER3 receptors may be critical in breast cancer growth and progression. Moreover, HER3 may provide a route for resistance to agents targeting EGFR or HER2. Although a number of studies have demonstrated that HER3 overexpression is associated with poor prognosis in patients with breast cancer, other studies have indicated that HER3 overexpression may be a positive prognostic factor. With respect to HER4 receptor, the existing evidence suggests that HER4 signalling promotes differentiation and growth inhibition of breast cancer cells. In addition, HER4 is more consistently related with a favourable prognosis in breast cancer. HER4 has multiple different activities in the breast, and many of these functions are mediated by a soluble HER4 intracellular domain. In addition, loss of HER4 expression may represent a marker for resistance to tamoxifen. Because of the functional interdependency among the HER receptors, it is possible that the effect on cell proliferation and tumor growth depends on receptor trans-signalling. Therefore, clarifying how and the extent to which these different signalling pathways interact in breast carcinogenesis, may lead to additional therapeutic opportunities. This review presents an update on the role of HER3 and HER4 receptors in breast cancer. Moreover, we provide current data relating to the prognostic significance of these receptors, as well as their impact on the activity of HER-targeting therapies in patients with breast cancer.

Semiconductor quantum dots for multiplexed bio-detection on solid-state microarrays - Corrected Proof

2009-05-21

Abstract: Understanding cellular systems requires identification and analysis of their multiple components and determination of how they act together and are regulated. Microarray technology is one of the few tools that is able to solve such problems. It is based on high-throughput recognition of a target to the probe and has the potential to simultaneously measure the presence of numerous molecules in multiplexed tests, all contained in a small drop of test fluid. Microarrays allow the parallel analysis of genomic or proteomic content in healthy versus disease-affected or altered tissues or cells. The signal read-out from the microarrays is done with organic dyes which often suffer of photobleaching, low brightness and background fluorescence. Recent data show that the use of fluorescent nanocrystals named “quantum dots” (QDs) allows to push these limits away. QDs are sufficiently bright to be detected as individual particles, extremely resistant against photobleaching and provide unique possibilities for multiplexing, thus supplying the microarray technology with a novel read-out option enabling the sensitivity of detection to reach the single-molecule level.This paper reviews QDs applications to microarray-based detection and demonstrates how the combination of microarray and QDs technologies may increase sensitivity and highly parallel capacities of multiplexed microarrays. Such a combination should provide the breakthrough results in drug discovery, cancer diagnosis and establish new therapeutic approaches through the identification of binding target molecules and better understanding of cell signalling pathways.