13331 articles - 10.09.10
1: Cancer. 2010 Sep 7; [Epub ahead of print]
Mattox A, Hughes B, Oleson J, Reardon D, McLendon R, Adamson C.
Department of Surgery (Division of Neurosurgery), Duke University Medical Center, Durham, North Carolina.
Primary extradural meningiomas (PEMs) represent about 2% of all meningiomas and are often encountered by non-neurosurgeons. These lesions typically present as enlarging, painless, benign masses that can be surgically cured. Imaging is critical for defining involvement of adjacent structures; however, diagnosis depends on classic histologic patterns. Treatment for benign PEMs (WHO I) consists of resection with wide margins, whereas adjuvant therapy after resection of atypical (WHO II) or malignant (WHO III) PEMs should be considered. By using the collective experience from our comprehensive cancer center, including neuro-oncologists, neuroradiologists, and neurosurgeons, in addition to a complete literature review, the authors have established treatment guidelines not previously reported. This manuscript describes key features of these challenging tumors to aid in diagnosis, presents the largest published review of all reported PEMs (n = 163), and provides salient treatment guidelines to surgeons unfamiliar with these challenging tumors. Cancer 2010. (c) 2010 American Cancer Society.
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PMID: 20824719 [PubMed - as supplied by publisher]2: Br J Cancer. 2010 Sep 7;103(6):861-9.
Weber GF, Lett GS, Haubein NC.
[1] University of Cincinnati Academic Health Center, James L. Winkle College of Pharmacy, 3225 Eden Avenue, Cincinnati, OH 45267-0004, USA [2] MetaMol Theranostics, Cincinnati, OH, USA.
Background:Only a fraction of molecular cancer markers identified in the scientific literature have found clinical use. Specifically, few predictors of invasiveness are established in diagnostics. Meta-analysis is a valuable tool for biomarker validation. Here, we evaluate Osteopontin as a marker for tumor aggressiveness (grade, stage, early progression) and patient survival.Methods:Publications through 2008 with the keywords 'osteopontin AND cancer' were retrieved. Titles and abstracts were screened for studies presenting original data on human subjects. This left 228 publications for data extraction. We applied categorical data analysis for testing the relationship between Osteopontin and a clinical variable.Results:Osteopontin ranks correlated with lower overall and disease-free/relapse-free survival in all tumors combined, as well as in lung cancer, breast cancer, prostate cancer, head and neck cancer, and liver cancer. Further, Osteopontin levels correlated with tumor grade and stage for all tumors combined and for several individual tumor types. Osteopontin levels were significantly associated with the early progression of eight cancers, independent in one, and inversely correlated in two.Conclusions:Osteopontin is significantly associated with survival in several forms of cancer. Osteopontin levels are also markers for stage, grade, and early tumor progression in multiple cancers, reflecting a common molecular underpinning for distinct clinical measures. Osteopontin has value as a clinical tumor progression marker.
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PMID: 20823889 [PubMed - in process]3: J Clin Oncol. 2010 Sep 7; [Epub ahead of print]
Chiu CW, Nozawa H, Hanahan D.
University of California, San Francisco, CA.
PURPOSE Pancreatic neuroendocrine tumors (PNETs), although rare, often metastasize, such that surgery, the only potentially curative therapy, is not possible. There is no effective systemic therapy for patients with advanced PNETs. Therefore, new strategies are needed. Toward that end, we investigated the potential benefit of dual therapeutic targeting of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a preclinical mouse model of PNET. Materials and METHODS Rapamycin and erlotinib, inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic mice bearing advanced multifocal PNET. Tumor growth and survival were monitored, and tumors were surveyed for potential biomarkers of response to the therapeutics. Results Rapamycin monotherapy was notably efficacious, prolonging survival concomitant with tumor stasis (stable disease). However, the tumors developed resistance, as evidenced by eventual relapse to progressive tumor growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal survival benefit. In combination, there was an unprecedented survival benefit in the face of this aggressive multifocal cancer and, in contrast to either monotherapy, the development of adaptive resistance was not apparent. Additionally, the antiapoptotic protein survivin was implicated as a biomarker of sensitivity and beneficial responses to the dual targeted therapy. CONCLUSION Preclinical trials in a mouse model of endogenous PNET suggest that combined targeting of the mTOR and EGFR signaling pathways could have potential clinical benefit in treating PNET. These results have encouraged development of an ongoing phase II clinical trial aimed to evaluate the efficacy of this treatment regimen in human neuroendocrine tumors.
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PMID: 20823411 [PubMed - as supplied by publisher]4: Cancer Res. 2010 Sep 7; [Epub ahead of print]
Palermo B, Del Bello D, Sottini A, Serana F, Ghidini C, Gualtieri N, Ferraresi V, Catricala C, Belardelli F, Proietti E, Natali PG, Imberti L, Nistico P.
Authors' Affiliations: Laboratory of Immunology, Department of Experimental Oncology and Department of Medical Oncology, Regina Elena National Cancer Institute; Melanoma Unit, Department of Dermatology-Oncology, S. Gallicano Dermatological Institute; Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy and Laboratory of Biotechnology, Diagnostic Department, Spedali Civili di Brescia, Brescia, Italy.
Combination of chemotherapy and immunotherapy to increase the effectiveness of an antitumor immune response is currently regarded as an attractive antitumor strategy. In a pilot clinical trial, we have recently documented an increase of melanoma antigen A (Melan-A)-specific, tumor-reactive, long-lasting effector-memory CD8(+) T cells after the administration of dacarbazine (DTIC) 1 day before peptide vaccination in melanoma patients. Global transcriptional analysis revealed a DTIC-induced activation of genes involved in the immune response and leukocyte activation. To identify the possible mechanisms underlying this improved immune response, we have compared the endogenous and the treatment-induced anti-Melan-A response at the clonal level in patients treated with the vaccine alone or with DTIC plus vaccine. We report a progressive widening of T-cell receptor (TCR) repertoire diversity, accompanied by high avidity and tumor reactivity, only in Melan-A-specific T-cell clones of patients treated with chemoimmunotherapy, with a trend toward longer survival. Differently, patients treated with vaccine alone showed a tendency to narrowing the TCR repertoire diversity, accompanied by a decrease of tumor lytic activity in one patient. Collectively, our findings indicate that DTIC plus vaccination shapes the TCR repertoire in terms of diversity and antitumor response, suggesting that this combined therapy could be effective in preventing melanoma relapse. Cancer Res; 70(18); 7084-92. (c)2010 AACR.
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PMID: 20823160 [PubMed - as supplied by publisher]5: Cancer. 2010 Sep 3; [Epub ahead of print]
Nemeth KM, Federico S, Carcaboso AM, Shen Y, Schaiquevich P, Zhang J, Egorin M, Stewart C, Dyer MA.
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee.
BACKGROUND:: The authors demonstrated previously that the combination of topotecan (TPT) and carboplatin (CBP) was more effective than current chemotherapeutic combinations used to treat retinoblastoma in an orthotopic xenograft model. However, systemic coadministration of these agents is not ideal, because both agents cause dose-limiting myelosuppression in children. METHODS:: To overcome the toxicity associated with systemic TPT and CBP, the authors explored subconjunctival delivery of TPT or CBP in an orthotopic xenograft model and in a genetic mouse model of retinoblastoma (Chx10-Cre;Rb(lox/lox);p107(-/-);p53(lox/lox)). The effects of combined subconjunctival CBP (CBP(subcon)) and systemic TPT (TPT(syst)) were compared with the effects of combined TPT(subcon) and CBP(syst) (.) at clinically relevant dosages. RESULTS:: Pharmacokinetic and tumor-response studies, including analyses of ocular and hematopoietic toxicity, revealed that CBP(subcon)/TPT(syst) was more effective and had fewer side effects than TPT(subcon)/CBP(syst). CONCLUSIONS:: For the first time, retinoblastoma was ablated and long-term vision was preserved in a mouse model by using a clinically relevant chemotherapy regimen. These results eventually may be translated into a clinical trial for children with this debilitating cancer. Cancer 2010. (c) 2010 American Cancer Society.
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PMID: 20818652 [PubMed - as supplied by publisher]6: Cancer. 2010 Sep 3; [Epub ahead of print]
Liu LC, Lang JE, Lu Y, Roe D, Hwang SE, Ewing CA, Esserman LJ, Morita E, Treseler P, Leong SP.
Department of Surgery, Helen Diller and Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California.
BACKGROUND:: Accurate intraoperative pathologic examination of sentinel lymph nodes (SLNs) has been an important tool that can reduce the need for reoperations in patients with SLN-positive breast cancer. The objective of the current study was to determine the accuracy of intraoperative frozen section (IFS) of SLNs during breast cancer surgery. METHODS:: The authors retrospectively reviewed the records of 326 patients with breast cancer who underwent IF analysis of SLNs at a single institution. Then, they conducted a meta-analysis that included 47 published studies of IFS of SLNs in patients with breast cancer. RESULTS:: Hematoxylin and eosin (H&E) staining revealed metastasis in SLNs in 99 patients (30.4%), including 61 patients with macrometastasis (MAM) (>2 mm) (the MAM group) and 38 patients with micrometastasis (Mi) or isolated tumor cell (ITC) deposits (the Mi/ITC group). The overall sensitivity of the institutional series was 60.6% (60 of 99 patients), and overall specificity was 100% (227 of 227 true negatives). The sensitivity of IFS was significantly lower in the Mi/ITC group (28.9%) than in the MAM group (80.3%; P < .0001). According to the meta-analysis of published studies and data from the author's institution (47 studies, for a total of 13,062 patients who underwent SLN dissection with IFS of SLNs), the mean sensitivity was 73%, and the mean specificity was 100%. The mean sensitivity was 94% for the MAM group and 40% for the Mi/ITC group. CONCLUSIONS:: IFS of SLNs was more reliable for detecting MAM than for detecting Mi/ITC deposits. It lacked sufficient accuracy to rule out Mi/ITC deposits. Cancer 2010. (c) 2010 American Cancer Society.
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PMID: 20818649 [PubMed - as supplied by publisher]7: Cancer Treat Rev. 2010 Sep 1; [Epub ahead of print]
Ramaekers BL, Pijls-Johannesma M, Joore MA, van den Ende P, Langendijk JA, Lambin P, Kessels AG, Grutters JP.
Department of Radiation Oncology (MAASTRO), GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 1588, 6201 BN Maastricht, The Netherlands.
PURPOSE: To synthesize and compare available evidence considering the effectiveness of carbon-ion, proton and photon radiotherapy for head and neck cancer. METHODS: A systematic review and meta-analyses were performed to retrieve evidence on tumor control, survival and late treatment toxicity for carbon-ion, proton and the best available photon radiotherapy. RESULTS: In total 86 observational studies (74 photon, 5 carbon-ion and 7 proton) and eight comparative in-silico studies were included. For mucosal malignant melanomas, 5-year survival was significantly higher after carbon-ion therapy compared to conventional photon therapy (44% versus 25%; P-value 0.007). Also, 5-year local control after proton therapy was significantly higher for paranasal and sinonasal cancer compared to intensity modulated photon therapy (88% versus 66%; P-value 0.035). No other statistically significant differences were observed. Although poorly reported, toxicity tended to be less frequent in carbon-ion and proton studies compared to photons. In-silico studies showed a lower dose to the organs at risk, independently of the tumor site. CONCLUSIONS: For carbon-ion therapy, the increased survival in mucosal malignant melanomas might suggest an advantage in treating relatively radio-resistant tumors. Except for paranasal and sinonasal cancer, survival and tumor control for proton therapy were generally similar to the best available photon radiotherapy. In agreement with included in-silico studies, limited available clinical data indicates that toxicity tends to be lower for proton compared to photon radiotherapy. Since the overall quantity and quality of data regarding carbon-ion and proton therapy is poor, we recommend the construction of an international particle therapy register to facilitate definitive comparisons. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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PMID: 20817407 [PubMed - as supplied by publisher]8: Cancer Treat Rev. 2010 Sep 1; [Epub ahead of print]
Oudard S, Beuselinck B, Decoene J, Albers P.
Oncology Department, Hopital Europeen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France.
Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor approved multinationally for the first- and second-line treatment of metastatic renal cell carcinoma (mRCC). The recommended dose of sunitinib is 50mg per day for 4weeks followed by 2weeks off-treatment (Schedule 4/2). In a phase III trial in 750 patients with mRCC who had not received prior treatment, sunitinib demonstrated superior efficacy to interferon-alpha for the first-line treatment of mRCC. Sunitinib doubled progression-free survival compared with interferon-alpha; furthermore, median OS with sunitinib was greater than 2years. As a result, sunitinib is now considered a reference standard of care for first-line mRCC treatment in patients at favourable or intermediate prognostic risk and is recommended in treatment guidelines. Additionally, results from an expanded-access programme, in a broad, heterogeneous patient population, confirmed the efficacy of sunitinib. Sunitinib has a distinct and predictable profile of adverse events, most of which are manageable with standard medical interventions. Therapy management strategies, including optimisation of dose and treatment duration and adverse event management can help patients achieve optimal efficacy with sunitinib in clinical practice. To further improve outcomes in patients with mRCC, current trials are evaluating sequencing or combination of targeted agents. The use of sunitinib as adjuvant therapy after nephrectomy and as neoadjuvant therapy is also being assessed. This paper provides an in-depth critical review of sunitinib, with particular focus on the data supporting the use of sunitinib for mRCC. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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PMID: 20817406 [PubMed - as supplied by publisher]9: Breast Cancer Res Treat. 2010 Aug 31; [Epub ahead of print]
Zreik TG, Mazloom A, Chen Y, Vannucci M, Pinnix CC, Fulton S, Hadziahmetovic M, Asmar N, Munkarah AR, Ayoub CM, Shihadeh F, Berjawi G, Hannoun A, Zalloua P, Wogan C, Dabaja B.
Department of Obstetrics and Gynecology, Lebanese American University, Beirut, Lebanon.
The risk of breast cancer has been associated with reproductive history. The purpose of this study was to determine the relationship between fertility drugs used in assisted reproductive procedures and the risk of breast cancer. We performed a literature search using the MEDLINE, the COCHRANE Library, and Scopus to identify studies linking breast cancer to fertility drugs. We excluded case series, case reports, and review articles from our analysis. The study populations included women who were treated for infertility with clomiphene, gonadotropins, gonadotropin-releasing hormones, or other unspecified fertility agents. We extracted information on study design, sample size, type of fertility drugs and number of treatment cycles, breast cancer incidence, and follow-up time from these studies. Eight case-control studies and fifteen cohort studies were included in the quantitative analyses. The Newcastle-Ottawa Quality Assessment Scales were used. Two investigators independently extracted study methods, sources of bias, and outcomes. We found that the risk of breast cancer was not significantly associated with fertility drug treatment. The follow-up periods were short in some of the studies analyzed in our study; however, we proceeded to test the trend in risk estimates across different durations of follow-up and found a trend for association using the nonparametric test; this was interpreted with caution in view of the lack of adjustment with other confounding factors. The current published data do not suggest higher risk of breast cancer in women who receive fertility treatment, but the lack of long-term follow up and the inherent weaknesses in some of the published studies have to be cautiously taken into account.
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PMID: 20809361 [PubMed - as supplied by publisher]10: Breast Cancer Res Treat. 2010 Sep 1; [Epub ahead of print]
Lu PH, Yang J, Li C, Wei MX, Shen W, Shi LP, Jiang ZY, Zhou N, Tao GQ.
Department of General Surgery, Wuxi People's Hospital of Nanjing Medical University, No. 299, Qingyang Road, Wuxi, 214023, Jiangsu, China, lphty1_1@yahoo.com.cn.
Published data on the association between mitogen-activated protein kinase kinase kinase 1 (MAP3K1) gene rs889312 polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of seven eligible articles including 26,015 cases and 33,962 controls based on the search criteria were involved in this meta-analysis. We observed that the MAP3K1 rs889312 polymorphism was significantly correlated with breast cancer risk from the fixed effects model when all studies were pooled into the meta-analysis (the allele contrast model: OR 1.09, 95% CI 1.07-1.12; the homozygote codominant: OR 1.22, 95% CI 1.15-1.29; the heterozygote codominant: OR 1.07, 95% CI 1.04-1.11; the dominant model: OR 1.10, 95% CI 1.06-1.13; the recessive model: OR 1.18, 95% CI 1.12-1.25). No significant association was found in the BRCA1 mutation carriers in all genetic models. When stratified by BRCA2 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (C vs. A: OR 1.12, 95% CI 1.01-1.23; CC vs. AA: OR 1.35, 95% CI 1.06-1.71; the recessive model: OR 1.31, 95% CI 1.05-1.65). There was no evidence for significant association between MAP3K1 rs889312 polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort for all comparison models. In conclusion, this meta-analysis suggests that the MAP3K1 rs889312 C allele is a low-penetrant risk factor for developing breast cancer, and there is limited evidence to indicate that MAP3K1 rs889312 polymorphism is associated with increased risk of breast cancer in BRCA1 mutation carriers.
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PMID: 20809358 [PubMed - as supplied by publisher]11: Cancer. 2010 Aug 27; [Epub ahead of print]
Vranic S, Teruya B, Repertinger S, Ulmer P, Hagenkord J, Gatalica Z.
Department of Pathology, Creighton University School of Medicine, Omaha, Nebraska.
BACKGROUND:: The current study was performed to determine the impact of polysomy 17 on the interpretation of HER2 testing of invasive breast carcinomas using fluorescent in situ hybridization methods. Current American Society of Clinical Oncology/College of American Pathologists guidelines define HER2-positive tumors as those with >6 HER2 genes per nucleus or those with HER2/CEP17 (chromosome 17) ratio >2.2. These guidelines are potentially contradictory in tumors with polysomy of chromosome 17. METHODS:: Seventy-two breast carcinoma cases with reported polysomy of chromosome 17 (>/=3 CEP17 signals on average) by fluorescent in situ hybridization were identified, and the corresponding HER2 immunohistochemistry was obtained. The HER2 status of the archived samples was reviewed, and the tumors were recategorized according to the 2007 American Society of Clinical Oncology/College of American Pathologists guidelines. RESULTS:: The average CEP17 copy number for the group was 4.5 (range, 3.0-10.4). Thirty-three (45.8%) cases had >6 copies of HER2 per nucleus. Twenty-one cases (29.2%) qualified as HER2 gene amplified using the HER2/CEP17 ratio (>2.2) guideline. All these cases had >6 HER2 signals, which represented 63.6% of all cases with >6 HER2 signals. HER2 protein expression showed significant positive correlations with both HER2 gene copy number and HER2/CEP17 ratio (P < .01, r(s) = 0.56 and 0.64, respectively). CONCLUSIONS:: Increased CEP17 signals detected in invasive breast carcinomas may lead to discordant interpretation of gene amplification in a significant proportion of the cases, depending on which criterion (ratio vs absolute number) is used for interpretation. However, increased gene dosage (>6 HER2 genes or HER2/CEP17 ratio >2.2), regardless of the evaluation method, is positively correlated with HER2 protein expression. Cancer 2010. (c) 2010 American Cancer Society.
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PMID: 20803611 [PubMed - as supplied by publisher]12: Breast Cancer Res Treat. 2010 Aug 26; [Epub ahead of print]
Li N, Bi X, Zhang Y, Zhao P, Zheng T, Dai M.
National Office for Cancer Prevention and Control, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China.
Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between HPV infection and risk of breast carcinoma, the studies remain inconclusive. Here, a meta-analysis was conducted to estimate the prevalence of HPV in breast carcinoma and test the association. Studies on HPV DNA detection in sporadic breast carcinoma in female using polymerase chain reaction were included. Information on overall and type-specific (HPV 6, 11, 16, 18, 31, 33, 35, 45 and 51) HPV prevalence were required, plus detailed descriptions of study populations, HPV DNA source, publication calendar period and PCR primers used for HPV DNA detection and typing. We revealed that 24.49% of the breast carcinoma cases were associated with HPV, 32.42% occurred in Asia and 12.91% in Europe. The four most commonly identified HPV types, in the order of decreased prevalence, were HPV33, 18, 16, and 35. The detection of HPV was mostly influenced by publication calendar period and PCR primers used. In addition, the analysis of ten case-control studies containing 447 breast carcinoma cases and 275 controls showed a significant increase in breast carcinoma risk with HPV positivity (OR = 3.63, 95% CI = 1.42-9.27). These results suggest that it's difficult to rule out the possibility of the association of HPV and breast carcinoma at present according to available publication proofs.
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PMID: 20740311 [PubMed - as supplied by publisher]13: Cancer. 2010 Aug 24; [Epub ahead of print]
Lara PN Jr, Chansky K, Shibata T, Fukuda H, Tamura T, Crowley J, Redman MW, Natale R, Saijo N, Gandara DR.
University of California Davis Cancer Center, Sacramento, California.
BACKGROUND:: Southwest Oncology Group 0124 was a large North American phase 3 trial that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with extensive stage small cell lung cancer (SCLC). These results were contrary to Japan Clinical Oncology Group 9511, a phase 3 trial exclusively in Japanese patients. Because 0124 and 9511 used identical treatment regimens and similar eligibility criteria, patient-level data were pooled from both trials, and a common arm analysis was performed to explore potential reasons for the divergent results. METHODS:: Patients with documented extensive stage SCLC and adequate end-organ function were randomized to intravenously receive either cisplatin 60 mg/m(2) Day 1 + irinotecan 60 mg/m(2) Days 1, 8, and 15 every 4 weeks or cisplatin 80 mg/m(2) Day 1 + etoposide 100 mg/m(2) Days 1-3 every 3 weeks. Demographic and outcome data were compared among 805 patients enrolled in 9511 and 0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status (PS). RESULTS:: Of 671 patients in 0124, 651 eligible patients were included, as were all 154 patients from 9511. Significant differences in sex and PS distribution as well as toxicity were seen between trials. There were also significant differences in response rates (87% vs 60%, P<.001) and median overall survival (12.8 vs 9.8 months, P<.001) when the cisplatin/irinotecan arms from both trials were compared. CONCLUSIONS:: Significant differences in patient demographics, toxicity, and efficacy were identified in the 9511 and 0124 populations. These results, relevant in the current era of clinical trials globalization, warrant: 1) consideration of differential patient characteristics and outcomes among populations receiving identical therapy; 2) utilization of the common arm model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected. Cancer 2010. (c) 2010 American Cancer Society.
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PMID: 20737417 [PubMed - as supplied by publisher]14: Breast Cancer Res Treat. 2010 Aug 25; [Epub ahead of print]
Yu KD, Chen AX, Yang C, Fan L, Huang AJ, Shao ZM.
Department of Breast Surgery, Cancer Center/Cancer Institute, Fudan University, 399 Ling-Ling Road, Shanghai, 200032, People's Republic of China.
The association between single-nucleotide polymorphisms (SNPs) in the interleukin-10 (IL-10) gene promoter and breast cancer risk is still ambiguous. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of the relationship between two genetic variants in the IL-10 gene promoter, -1082A > G (rs1800896) and -592C > A (rs1800872), and breast cancer. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the corresponding strengths of association under the codominant, dominant, and recessive models. A total of ten studies (4,181 cases and 4,384 controls) were eligible for meta-analysis. There were six studies with 3,032 cases and 3,190 controls for rs1800872, and eight studies with 1,636 cases and 1,670 controls for rs1800896. Meta-analysis showed that neither of the two polymorphisms had any association with increased breast cancer risk (for rs1800896: OR = 1.060, 95% CI = 0.785-1.432 in the dominant model, and OR = 1.152, 95% CI = 0.958-1.386 in the recessive model; and for rs1800872: OR = 0.952, 95% CI = 0.859-1.056 in the dominant model, and OR = 0.892, 95% CI = 0.741-1.072 in the recessive model). The results did not change when the analyses were restricted in Caucasians, or in the studies fulfilling Hardy-Weinberg equilibrium, or according to source of controls. In outlier analysis, no individual study affected the overall OR dominantly, since omission of any single study made no material huge difference. In conclusion, the present meta-analysis suggests a lack of association between the two SNPs (rs1800896 and rs1800872) in the IL-10 gene promoter and breast cancer risk. Further studies, either with larger sample size or regarding other SNPs/haplotypes within the IL-10 gene, are needed to clarify the role of IL-10 in breast carcinogenesis.
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PMID: 20737205 [PubMed - as supplied by publisher]15: BMC Cancer. 2010 Aug 24;10:457.
Dollinger MM, Lautenschlaeger C, Lesske J, Tannapfel A, Wagner AD, Schoppmeyer K, Nehls O, Welker MW, Wiest R, Fleig WE; AIO Hepatobiliary Study Group.
Department of Medicine (I), Martin-Luther-University Halle-Wittenberg, Germany. matthias.dollinger@medizin.uni-halle.de.
ABSTRACT: BACKGROUND: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. METHODS: The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky >/=60%/Child-Pugh </= 12) were randomised to receive thymostimulin 75 mg s.c. 5x/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol. RESULTS: Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. CONCLUSIONS: In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64487365.
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PMID: 20735834 [PubMed - in process]16: Cancer. 2010 Aug 23; [Epub ahead of print]
Danese MD, Lalla D, Brammer M, Doan Q, Knopf K.
Outcomes Insights, Inc., Newbury Park, California.
BACKGROUND.: Breast cancer recurrence is associated with significant morbidity, mortality, and cost. Patients with early stage HER2+ tumors are at increased risk of recurrence. The use of trastuzumab for these patients has been shown to reduce recurrences and improve overall survival. METHODS.: A Monte Carlo simulation was conducted based on Surveillance, Epidemiology, and End Results incidence rates for 2005, United States Census data for 2005, and the results of key trials of the adjuvant use of trastuzumab. Patients included in this analysis had incident, HER2+, stage I to III breast cancer. The number of recurrences that could be prevented with trastuzumab, the cardiac adverse events that might occur, and the associated cost savings were estimated. RESULTS.: Approximately 31,200 women had HER2+ breast cancer in 2005, of whom 7298 would have had a recurrence over the subsequent 5 years despite standard of care adjuvant treatment. If trastuzumab were added to their regimen, 2791 women might have avoided recurrence, and 948 may have had an asymptomatic or symptomatic cardiac adverse event, for a ratio of expected recurrences to cardiac adverse events of 3.2 (95% confidence interval, 1.5-5.9). In economic terms, avoidance of future breast cancer recurrences was associated with lifetime reduction in future direct and indirect costs on the order of $240 million to $1.7 billion. CONCLUSIONS.: On the basis of the simulation results, targeting HER2+ tumors with trastuzumab in the adjuvant setting should prevent a significant number of women from recurrence events, with important outcomes for patients, physicians, payers, and society. Cancer 2010. (c) 2010 American Cancer Society.
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PMID: 20734398 [PubMed - as supplied by publisher]17: BMC Cancer. 2010 Aug 17;10:436.
Riemsma R, Simons JP, Bashir Z, Gooch CL, Kleijnen J.
Kleijnen Systematic Reviews Ltd,, York, UK. rob@systematic-reviews.com
BACKGROUND: To undertake a systematic review of the available data for oral and intravenous topotecan in adults with relapsed small cell lung cancer (SCLC) for whom re-treatment with the first line regimen is not considered appropriate. METHODS: We searched six databases from 1980 up to March 2009 for relevant trials regardless of language or publication status. Relevant studies included any randomised trial of any chemotherapeutic treatment against any comparator in this licensed indication. Where possible we used opposite quantitative methods. Where meta-analysis was considered unsuitable for some or all of the data, we employed a narrative synthesis method. For indirect comparisons we used the method of Bucher et al., where available data allowed it, otherwise we used narrative descriptions. RESULTS: Seven unique studies met the inclusion criteria, four of which could be used in our analyses. These included one study comparing oral topotecan plus best supportive care (BSC) to BSC alone, one study comparing intravenous topotecan to cyclophosphamide, adriamycin and vincristine (CAV), and two studies comparing oral topotecan with intravenous topotecan. All four studies appear to be well conducted and with low risk of bias. Oral topotecan plus BSC has advantages over BSC alone in terms of survival (hazard ratio = 0.61; 95% CI, 0.43 to 0.87) and quality of life (EQ-5 D difference: 0.15; 95% CI, 0.05 to 0.25). Intravenous topotecan was at least as effective as CAV in the treatment of patients with recurrent small-cell lung cancer and resulted in improved quality-of-life with respect to several symptoms. CAV was associated with significantly less grade 4 thrombocytopenia compared with IV topotecan (risk ratio = 5.83; 95% CI, 2.35 to 14.42). Survival (hazard ratio = 0.98; 95% CI, 0.77 to 1.25) and response (pooled risk ratio = 1.04; 95% CI, 0.58 to 1.85) data were similar for the oral and IV topotecan groups. Symptom control was also very similar between the trials and between the oral and IV groups. Toxicity data showed a significant difference in favour of oral topotecan for neutropenia (pooled risk ratio = 0.65; 95% CI, 0.47 to 0.89). Indirect evidence showed that oral topotecan was at least as good as or better than CAV on all outcomes (survival, response rates, toxicities, and symptoms) that allowed indirect comparisons, with the only exception being grade four thrombocytopenia which occurred less often on CAV treatment. CONCLUSIONS: Concerning topotecan both the oral and intravenous options have similar efficacy, and patient preference may be a decisive factor if the choice would be between the two formulations. The best trial evidence for decision making, because it was tested versus best supportive care, exists for oral topotecan. Indirectly, because we have two head-to-head comparisons of oral versus intravenous topotecan, and one comparison of intravenous topotecan versus CAV in similar patients as in the trial against best supportive care, one might infer that IV topotecan and CAV could also be superior to best supportive care, and that oral topotecan has similar effects to CAV with possibly better symptom control. From the evidence discussed above, it is evident that oral topotecan has similar efficacy to IV topotecan (direct comparison) and CAV (indirect comparison). There is no further evidence base of direct or possible indirect comparisons for other comparators than CAV of either oral or IV topotecan.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20716361&dopt=ExternalLink
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PMID: 20716361 [PubMed - in process]18: Breast Cancer Res Treat. 2010 Aug 15; [Epub ahead of print]
Vrieling A, Buck K, Kaaks R, Chang-Claude J.
Division of Cancer Epidemiology, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany, a.vrieling@dkfz-heidelberg.de.
Adult weight gain is positively associated with postmenopausal breast cancer and inversely associated with premenopausal breast cancer risk. To date, no meta-analysis has been conducted to assess this association by estrogen receptor (ER) and progesterone receptor (PR) status. We searched PubMed for relevant studies published through March 2010. Summarized risk estimates (REs) with 95% confidence intervals (CIs) were calculated using random effects or fixed effects models. We retrieved nine articles on weight gain from adulthood to reference age and ER- and/or PR-defined breast cancer risk, reporting on three prospective cohort studies and eight case-control studies. Comparing the highest versus the lowest categories of adult weight gain, risk was increased for ER(+)PR(+) and ER(+) tumors combined (11 studies; RE = 2.03; 95% CI 1.62, 2.45). Statistically significant heterogeneity (p (heterogeneity) = 0.002) was shown between REs for a mixed population of pre- and postmenopausal women combined (4 studies; RE = 1.54; 95% CI 0.86, 2.22) and for postmenopausal women only (7 studies; RE = 2.33; 95% CI 2.05, 2.60). Risk for ER(-)PR(-) tumors among postmenopausal women was also slightly increased (7 studies; RE = 1.34; 95% CI 1.06, 1.63), but statistically significantly different from risk for ER(+)PR(+) tumors (p (heterogeneity) < 0.0001). No associations were observed for ER(+)PR(-) tumors whereas risk for ER(-)PR(+) tumors could not be assessed. In conclusion, the association between adult weight gain and postmenopausal breast cancer risk is heterogeneous according to ER/PR status and stronger for ER(+)PR(+) than for ER(-)PR(-) tumors.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20711809&dopt=ExternalLink
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PMID: 20711809 [PubMed - as supplied by publisher]19: Cancer Treat Rev. 2010 Aug 13; [Epub ahead of print]
Hartwell D, Jones J, Loveman E, Harris P, Clegg A, Bird A.
Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, First Floor Epsilon House, Enterprise Road, Southampton Science Park, Southampton SO16 7NS, UK.
BACKGROUND: Topotecan is a relatively new drug for use as a second-line treatment in patients with relapsed small cell lung cancer (SCLC). We performed a systematic review and economic evaluation of topotecan, and consider it here in relation to the NICE end of life criteria. METHODS: Seventeen bibliographic databases (including Cochrane library, Medline and Embase) were searched from 1990 to February 2009, and experts and manufacturers were consulted, to identify relevant randomised controlled trials (RCTs) which were selected according to prospectively defined criteria. An economic evaluation was undertaken to assess cost effectiveness compared with best supportive care (BSC) in the UK. RESULTS: Five RCTs were included. The clinical evidence indicates a statistically significant benefit of oral topotecan plus BSC compared to BSC alone for overall survival. Intravenous topotecan was similar in efficacy to both oral topotecan and CAV (cyclophosphamide, doxorubicin and vincristine). In the survival model, oral topotecan plus BSC was associated with an average gain in life expectancy of approximately 4months, resulting in a gain of 0.183 quality-adjusted life years (QALYs). At an incremental cost of approximately pound6200 the incremental cost effectiveness ratio (ICER) is pound33,851 per QALY gained. CONCLUSIONS: Compared with BSC alone, oral topotecan for patients with relapsed SCLC was associated with improved health outcomes but at increased cost. The ICER is at the upper extreme of the range conventionally regarded as cost effective from an NHS decision making perspective. However, this treatment may fall under supplementary guidance for life extending, end of life treatments. Crown Copyright (c) 2010. Published by Elsevier Ltd. All rights reserved.
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PMID: 20709456 [PubMed - as supplied by publisher]20: Breast Cancer Res Treat. 2010 Aug 12; [Epub ahead of print]
Chen MB, Wu XY, Shen W, Wei MX, Li C, Cai B, Tao GQ, Lu PH.
Department of Oncology, Kunshan People's Hospital Affiliated To Jiangsu University, No. 91, Qianjin Road, Kunshan, 215300, Jiangsu, China.
Trinucleotide repeat containing 9 (TNRC9) is a gene located at chromosome 16q12. Although of an uncertain function, it is a newly described risk factor for breast cancer. It contains a putative high-mobility group box motif, suggesting its possible role as transcription factor; it has been implicated in breast cancer metastasis. Published studies on the association between TNRC9 polymorphisms and breast cancer risk remain inconclusive, and a meta-analysis is required to verify the association. This pioneering research performed a meta-analysis of eight studies comprising a total of 25,828 cases and 36,177 controls. Significantly elevated breast cancer risk was associated with TNRC9 rs3803662 polymorphism when all studies were pooled in the meta-analysis (T vs. C allele contrast model: OR 1.18, 95% CI 1.09-1.28; TT vs. CC homozygote codominant model: OR 1.26, 95% CI 1.02-1.55; TT vs. CC+CT recessive model: OR 1.23, 95% CI 1.06-1.42). For TNRC9 rs12443621 polymorphism, no significant association was detected in all genetic models. For TNRC9 rs12443621 polymorphism, meanwhile, no significant association was observed in all comparison models. Conclusively, this meta-analysis suggests that TNRC9 rs3803662 polymorphism was significantly correlated with breast cancer risk and the variant T allele of TNRC9 rs3803662 polymorphism is a low-penetrant risk factor for developing breast cancer. There is no significant association between TNRC9 rs12443621 and rs8051542 polymorphisms and risk of breast cancer in current literature.
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PMID: 20703937 [PubMed - as supplied by publisher]