Background.
There are concerns about growing barriers to cancer research. We explored the characteristics of and barriers to global clinical cancer research.
Methods.
The American Society of Clinical ...Oncology International Affairs Committee invited 300 selected oncologists with research experience from 25 countries to complete a Web‐based survey. Fisher's exact test was used to compare answers between participants from high‐income countries (HICs) and low‐ and middle‐income countries (LMICs). Barriers to clinical cancer research were ranked from 1 (most important) to 8 (least important). Mann‐Whitney's nonparametric test was used to compare the ranks describing the importance of investigated obstacles.
Results.
Eighty oncologists responded, 41 from HICs and 39 from LMICs. Most responders were medical oncologists (62%) at academic hospitals (90%). Researchers from HICs were more involved with academic and industry‐driven research than were researchers from LMICs. Significantly higher proportions of those who considered their ability to conduct academic research and industry‐driven research over the past 5 years more difficult were from HICs (73% vs. 27% and 70% vs. 30%, respectively). Concerning academic clinical cancer research, a lack of funding was ranked the most important (score: 3.16) barrier, without significant differences observed between HICs and LMICs. Lack of time or competing priorities and procedures from competent authorities were the second most important barriers to conducting academic clinical research in HICs and LMICs, respectively.
Conclusion.
Lack of funding, lack of time and competing priorities, and procedures from competent authorities might be the main global barriers to academic clinical cancer research.
摘要
背景. 越来越多的癌症研究障碍引起了全球关注。本文探索了全球临床癌症研究的特征及其障碍。
方法. 美国临床肿瘤学会国际事务委员会从25个国家中遴选并邀请了300位具有研究经验的肿瘤科医生来完成一项网上调查。使用Fisher确切概率法来比较来自高收入国家（HIC）与低至中等收入国家（LMIC）参与者之间所提供的答案。临床癌症研究的各项障碍被分为1级（非常重要）到8级（最不重要）。通过Mann‐Whitney非参数检验来比较纳入调查的障碍的重要性等级。
结果. 80位肿瘤科医生作出应答，其中41位来自HIC，39位来自LMIC。大多数应答者为就职于学术性医院（90%）的肿瘤内科医生（62%）。来自HIC的研究者在学术研究以及产业驱动的研究方面参与程度高于来自LMIC的研究者。有显著更高比例的HIC研究者认为，在过去的5年内开展学术研究以及产业驱动的研究 所面临的困难更大（与LMIC研究者相比，分别为73% vs. 27% 、70% vs. 30%）。就学术性临床癌症研究而言，缺乏资金被列为最重要（评分3.16）的障碍，HIC研究者与LMIC研究者之间未观察到显著差异。时间不够多或相互竞争的优先级以及监管当局的审批流程分别被HIC与LMIC列为第二重要的障碍。
结论. 缺乏资金和时间、相互竞争的优先级以及监管当局审批流程可能是学术性临床癌症研究所面临的全球性障碍。The Oncologist 2014;19:1‐7
Using data from the American Society of Clinical Oncology International Affairs Committee's Web survey of selected oncologists with research experience from 25 countries, the authors explored the characteristics of and barriers to global clinical cancer research. They concluded that lack of funding, lack of time and competing priorities, and procedures from competent authorities might be the main global barriers to academic clinical cancer research.
Background. Chemotherapy with platinum agent and etoposide for small-cell lung cancer (SCLC) is supposed to be associated with intermediate risk (10-20%) of febrile neutropenia. Primary prophylaxis ...with granulocyte colonystimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice febrile neutropenia is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of neutropenia and febrile neutropenia in advanced SCLC patients in the first cycle of standard chemotherapy. Furthermore, we explored the association between severe neutropenia and etoposide peak plasma levels in the same patients.
Methods. The case series based analysis of 17 patients with advanced SCLC treated with standard platinum/etoposide chemotherapy, already included in the pharmacokinetics study with etoposide, was performed. Grade 3/4 neutropenia and febrile neutropenia, observed after the first cycle are reported. The neutrophil counts were determined on day one of the second cycle unless symptoms potentially related to neutropenia occurred. Adverse events were classified according to Common Toxicity Criteria 4.0. Additionally, association between severe neutropenia and etoposide peak plasma concentrations, which were measured in the scope of pharmacokinetic study, was explored.
Results. Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient who did not receive primary prophylaxis the rates of both grade 3/4 neutropenia and febrile neutropenia were high (8/15 (53.3%) and 2/15 (13.3%), respectively), already in the first cycle of chemotherapy. One patient died due to febrile neutropenia related pneumonia. Neutropenic events are assumed to be related to increased etoposide plasma concentrations after a standard etoposide and cisplatin dose. While the mean etoposide peak plasma concentration in the first cycle of chemotherapy was 17.6 mg/l, the highest levels of 27.07 and 27.49 mg/l were determined in two patients with febrile neutropenia.
Conclusions. Our study indicates that there is a need to reduce the risk of neutropenic events in chemotherapy treated advanced SCLC, starting in the first cycle. Mandatory use of primary G-CSF prophylaxis might be considered. Alternatively, use of improved risk models for identification of patients with increased risk for neutropenia and individualization of primary prophylaxis based on not only clinical characteristics but also on etoposide plasma concentration measurement, could be a new, promising options that deserves further evaluation.
Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM ...aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1-FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1-4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1-4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not sufficient to predict FGFR inhibitor response in MPM cell lines.
The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. ...Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages.
The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty.
The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P =.03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis.
Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population.
In the last decade, major progress in the treatment of advanced non-small-cell lung cancer has been made through the better understanding of the molecular biology of lung cancer, identification of ...new oncogene drivers and development of oncogene-directed drugs. Oncogene-directed therapies with EGFR or anaplastic lymphoma kinase tyrosine kinase inhibitors became standard practice in patients with activating EGFR mutations or anaplastic lymphoma kinase rearrangements, improving median survival rates to up to 35 months. Encouragingly, there are still numerous other targeted drugs and treatment strategies under development. In addition, nowadays chemotherapy can be tailored based on histology of the primary tumor and response to induction chemotherapy, raising median survival rates up to 13 months. These major developments, both in oncogene- and non-oncogene-directed therapies is presented in this review, together with a further designation of the most relevant future strategies, such as immunotherapy.
Proteases and metastasis: clinical relevance nowadays? Decock, Julie; Paridaens, Robert; Čufer, Tanja
Current opinion in oncology,
2005-November, 2005-Nov, 2005-11-00, 20051101, Letnik:
17, Številka:
6
Journal Article
PURPOSE OF REVIEWA great deal of breast cancer research has been devoted to the search for new prognostic and predictive markers which could, on the one hand, enable a more precise identification of ...patients at high risk of recurrence and, on the other hand, predict the response of each individual patient to the administered therapy. Proteases have been the center of interest because of their prominent involvement in cancer progression and metastasis. In particular, the matrix metalloproteinases, the serine protease urokinase plasminogen activator, the cathepsins, and corresponding inhibitors have been studied extensively. This article reviews the developments during the last year in this field.
RECENT FINDINGSThe prognostic effect of urokinase plasminogen activator and plasminogen activator inhibitor 1 was confirmed in a meta-analysis and in a prospective randomized clinical study that provided level 1 evidence for the clinical value of these markers. Furthermore, encouraging data suggest that both urokinase plasminogen activator and plasminogen activator inhibitor 1 might be important predictive markers. To date, findings on the prognostic and predictive value of the matrix metalloproteinases, the cathepsins, and their inhibitors are still inconclusive.
SUMMARYOn the basis of currently available data, tumor urokinase plasminogen activator and plasminogen activator inhibitor 1 levels could already be used in everyday clinical practice for selection of candidates for adjuvant systemic therapy. Further effort should be put into the standardization of the matrix metalloproteinases and cathepsins determination so that their clinical relevance in breast cancer can be defined.
Background
Immunotherapy with immune checkpoint inhibitors (ICIs) recently became the standard treatment for patients with advanced non‐small cell lung cancer (NSCLC). Here, we present the first ...results of a real‐world observational study on the effectiveness of ICI monotherapy in patients with advanced NSCLC treated at a single academic center in a Central and Eastern European (CEE) country.
Materials and Methods
Overall, 66 consecutive patients with advanced NSCLC treated with ICIs in everyday clinical practice, either with first‐line pembrolizumab (26 patients) or second‐line atezolizumab, nivolumab, or pembrolizumab (40 patients), from August 2015 to November 2018, were included. All data were retrieved from a hospital lung cancer registry, in which the data is collected prospectively.
Results
Included patients had a median age of 64 years, most were male (55%), 6% were in performance status ≥2, and 18% had controlled central nervous system metastases at baseline. In first‐line, the median progression‐free survival (mPFS) was 9.3 months, while the median overall survival (mOS) was not reached. The 1‐year overall survival (OS) was 62%. In second‐line, the mPFS and mOS were 3.5 months and 9.9 months, respectively, with a 1‐year OS of 35%. In the overall population, adverse events of any grade were recorded in 79% of patients and of severe grade (3–4) in 12% of patients.
Conclusion
The first real‐world outcomes of NSCLC immunotherapy from a CEE country suggest comparable effectiveness to those observed in clinical trials and other real‐world series, mainly coming from North America and Western European countries. Further data to inform on the real‐world effectiveness of immunotherapy worldwide are needed.
Implications for Practice
Immunotherapy is a standard treatment of advanced non‐small cell lung cancer (NSCLC). The real‐world data on immunotherapy are still limited. This article presents the first data on the effectiveness of mono‐immunotherapy with immune checkpoint inhibitors for patients with advanced NSCLC treated at a single academic center in a Central and Eastern European country. The survival rates and toxicity are comparable to those achieved in randomized clinical trials and other real‐world series, coming mainly from North American and Western European countries. There is a pressing need to gather further data on the effectiveness of immunotherapy in everyday practice worldwide.
Immunotherapy has become the standard treatment for advanced non‐small cell lung cancer (NSCLC). This article presents the first real‐world results on the effectiveness of immune checkpoint inhibitor treatment for advanced NSCLC from a single academic center from Central and Eastern European country.
Concurrent vinablastine-based radiochemotherapy was evaluated in 84 bladder-cancer patients. It was effective in more than half: tumour-specific survival (51% 9-year), local control rate (55% ...9-year). The drawback was the impaired function of the bladder (9-year prevalence SOMA G3-4 symptoms: 66%), indicating the need for treatment aimed at reducing chronic morbidity.
Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this ...association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination. In this substudy, we evaluated whether patients with diabetes at study entry-with or without metformin treatment-were associated with different disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) compared with patients without diabetes. Results A total of 8,381 patients were included in the current analysis: 7,935 patients (94.7%) had no history of diabetes at diagnosis, 186 patients (2.2%) had diabetes with no metformin treatment, and 260 patients (3.1%) were diabetic and had been treated with metformin. Median follow-up was 4.5 years (0.16 to 6.31 years), at which 1,205 (14.38%), 929 (11.08%), and 528 (6.3%) patients experienced DFS, DDFS, and OS events, respectively. Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio HR, 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004). This effect was limited to hormone receptor-positive patients. Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor-positive breast cancer. Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor-positive breast cancer.
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