Fairness-aware machine learning engineering: how far are we?

Machine learning is part of the daily life of people and companies worldwide. Unfortunately, bias in machine learning algorithms risks unfairly influencing the decision-making process and reiterating possible discrimination. While the interest of the software engineering community in software fairness is rapidly increasing, there is still a lack of understanding of various aspects connected to fair machine learning engineering, i.e., the software engineering process involved in developing fairness-critical machine learning systems. Questions connected to the practitioners' awareness and maturity about fairness, the skills required to deal with the matter, and the best development phase(s) where fairness should be faced more are just some examples of the knowledge gaps currently open. In this paper, we provide insights into how fairness is perceived and managed in practice, to shed light on the instruments and approaches that practitioners might employ to properly handle fairness. We conducted a survey with 117 professionals who shared their knowledge and experience highlighting the relevance of fairness in practice, and the skills and tools required to handle it. The key results of our study show that fairness is still considered a second-class quality aspect in the development of artificial intelligence systems. The building of specific methods and development environments, other than automated validation tools, might help developers to treat fairness throughout the software lifecycle and revert this trend.

The PI3k inhibitors: new hopes in the battle against advanced NSCLC.

In terms of both incidence and mortality, lung tumor is the most common cancer in the world today. Among lung tumors, 80% are classified as non-small-cell lung cancer (NSCLC) and are mostly diagnosed at an advanced stage (either locally advanced or metastatic disease). Platinum-based doublet chemotherapy, the standard treatment for advanced NSCLC, has reached a plateau of effectiveness and achieves mostly partial responses in only 30%-40% of patients and a modest survival increase. Thus, the search for new molecularly targeted therapies is mandatory. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently over activated in human cancers playing a critical role both in the initiation and progression of NSCLC. Activating mutations of this pathway play a role in the development of resistance to chemotherapy and to the Epidermal Growth Factor Receptor Tyrosine Kinase inhibitors (EGFR-TKIs) erlotinib and gefitinib. These mutations are observed in 2-5 % of non-squamous NSCLC and 8-10 % of squamous NSCLC. In this paper, we describe the available data and the possible future role of PI3k inhibitors in the treatment of advanced NSCLC.

ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC.

The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of patients with advanced non-small cell lung cancer (NSCLC). Oncogenic fusion genes, including echinoderm microtubule-associated protein-like 4 (EML4) and ALK, have been detected in approximately 2-7 % of NSCLC patients. Fluorescence in situ hybridization (FISH) is the recommended method for detecting ALK gene rearrangement. EML4-ALK fusion genes define a molecular subset of NSCLC with distinct clinical characteristic (lung adenocarcinoma, never or former smoker, usually mutually exclusive with EGFR mutations). Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive, small molecule inhibitor of both the receptor tyrosine kinases ALK and c-MET (hepatocyte growth factor receptor). Crizotinib has been shown to yield important clinical benefit such as objective response rate, progression-free survival (PFS), and anticipated improvements in quality of life when used in pretreated patients with advanced NSCLC harboring EML4-ALK gene rearrangement. Preliminary phase II data suggested that crizotinib is safe and well tolerated with rapid and robust antitumor activity. A phase III randomized trial in a second-line setting showed response rate and PFS (primary study endpoint) advantage for crizotinib as compared to second-line chemotherapy. Treatment-related adverse events, predominantly restricted to the gastrointestinal and visual systems, are generally self-limiting or easily managed. Crizotinib is a new standard of care for patients with advanced, ALK-positive, NSCLC. In this review, we will discuss the discovery of ALK rearrangements, the clinical epidemiology of lung cancer driven by ALK, the clinical data for ALK-targeted therapy in NSCLC, and ongoing ALK inhibitor-based clinical trials.

Recent developments of targeted therapies in the treatment of non-small cell lung cancer.

Non small cell lung cancer (NSCLC) is a lethal disease with poor prognosis. The main percentage of NSCLC patients are diagnosed to have an advanced disease. Standard treatment, such as chemotherapy and radiotherapy, has apparently reached a plateau of effectiveness in improving survival of advanced NSCLC patients. Hence, considerable efforts have started to be made in order to identify novel targets for new biological agents which may safely and effectively be administered to advanced NSCLC patients. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) and its receptors play an essential role in tumour proliferation. Approaches targeting EGFR and VEGF include monoclonal antibodies (mAbs) and small molecules inhibiting the corresponding receptor-tyrosine kinase activity. Erlotinib is a small molecule inhibitor of EGFR tyrosine-kinase which has brought significant improvements in median survival, quality of life and related symptoms, in an unselected population of advanced NSCLC patients in the second- or third-line setting. Bevacizumab, an anti-VEGF recombinant humanized mAb, is the first targeted agent which, when combined with chemotherapy, reported superior efficacy versus chemotherapy alone in the treatment of advanced NSCLC. ZD6474, a small molecule targeting VEGF tyrosine-kinase activity, showing early evidence of antitumour activity and the excellent toxicity profile, seems to be a promising agent for the treatment of advanced NSCLC. This review shows the latest and the future developments of erlotinib, bevacizumab and ZD6474 in the treatment of advanced NSCLC patients.

New insights in drug development for the non-small cell lung cancer therapy.

Non-small cell lung cancer (NSCLC) remains a major problem worldwide. Since most patients with NSCLC have advanced disease at diagnosis, to date, chemotherapy, with third-generation platinum-based doublets, represents the standard of care. However, a plateau has been reached with the use of cytotoxic chemotherapy in advanced NSCLC. Advances in the knowledge of tumour biology and mechanisms of oncogenesis have granted the singling out of several molecular targets for NSCLC treatment. To date, erlotinib and gefitinib, epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors have been licensed, erlotinib worldwide and gefitinib in Asian countries, for refractory NSCLC. Currently, bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, is the only clinically available antiangiogenic agent licensed, in combination with carboplatin plus paclitaxel, for first-line therapy of advanced NSCLC patients in the United States. Several new biologic agents are being evaluated in clinical research and some of them, such as ZD6474, sorafenib and sunitinib, due to the reported preliminary results and the oral administration seem to be promising targeted agents for the treatment of NSCLC. Aim of this review is to discuss about the new insights in targeted agents development for the treatment of NSCLC patients.

Erlotinib in non-small-cell lung cancer.

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting. Erlotinib is well tolerated (with common toxicities including rash and diarrhoea) when administered at a standard oral daily dose of 150 mg. Further investigations are ongoing to contribute to our understanding of the role of erlotinib in NSCLC treatment.

Three cases of long-lasting tumor control with erlotinib after progression with gefitinib in advanced non-small cell lung cancer.

INTRODUCTION: We report the cases of three patients with advanced non-small cell lung cancer responding to erlotinib after progression under gefitinib treatment. METHODS: Three never-smoker women with advanced lung adenocarcinoma, two pretreated with chemotherapy and with gefitinib and one with gefitinib alone, received erlotinib in a daily dose of 150 mg. All three patients had disease progression and had achieved tumor control with gefitinib. RESULTS: The first patient achieved partial response of lung lesions, the second had partial response of brain lesions and stable disease of lung and bone disease, and the third had partial response of brain lesions and stable disease of lung disease. At the time of this analysis, all three patients were still receiving treatment with erlotinib with no evidence of treatment failure after more than 13, 13, and 7 months, respectively. Erlotinib was generally well tolerated, with grade 1 skin toxicity recorded in two patients. CONCLUSIONS: Erlotinib may be effective in patients with non-small cell lung cancer who were previously and successfully treated with gefitinib. However, careful selection of these patients is needed.

Informal caregiving burden in advanced non-small cell lung cancer: the HABIT study.

INTRODUCTION: This study's aim was to assess economic data regarding the home assistance burden for advanced non-small cell lung cancer (NSCLC) patients in Italy. PATIENTS AND METHODS: One hundred four NSCLC patients in second-line chemotherapy (2LC) or in supportive therapy (ST) were enrolled in 18 Italian oncology departments and were observed for 3 months. The main caregiver's workload was assessed monthly by a task scale; other caregivers' activities were also registered. Eastern Cooperative Oncology Group performance status was assessed by physicians, and patients completed the Lung Cancer Symptoms (LCS) subscale. Formal caregiving time was valued according to market prices; informal caregiving hours were valued using the wage rate for an equivalent service. Covariance analysis was performed to check for influential factors in assistance costs. RESULTS: The mean age of the total sample was 65.5 years, and prevalence of males was over 80%. In over 70% of cases, the principal caregiver was patient's spouse, living with the patient and not working. Principal caregiver support was the main cost item: 2.368 euros in 2LC and 2.805 euros in ST, representing 74% of total trimonthly assistance costs. Regression analysis showed a positive correlation between the severity of symptoms and the costs of assistance. The caregiving burden was higher in patients with bone and/or cerebral metastases; other metastasis sites seemed to have no impact on assistance costs. CONCLUSION: Considering quality of life as the ultimate health outcome, clinicians are challenged to contribute to a research and policy agenda that holds burden of care in due consideration.

Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer.

Despite the optimization of chemotherapy regimens, treatment outcomes for advanced non-small cell lung cancer (NSCLC) are still considered to be disappointing. Thus, clinical research of new treatment strategies is warranted. Several targeted agents have been introduced into clinical trials in NSCLC, but to date, only a few of these new agents can offer hope of a substantial impact on the natural history of the disease. One of the main reasons for the failure of several clinical trials of targeted therapy in lung cancer is that there is multilevel cross-stimulation among the targets of the new biological agents along several pathways of signal transduction that lead to neoplastic events; blocking only one of these pathways, as most first-generation targeted agents do, allows others to act as salvage or escape mechanisms for cancer cells. Sorafenib and sunitinib are two oral multitargeted receptor tyrosine kinase inhibitors. Sorafenib is a multikinase inhibitor that inhibits the kinase activity of both C-RAF and B-RAF and targets the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and stem cell factor receptor [KIT]). Sunitinib is a multitargeted inhibitor of PDGFR, KIT, fms-like tyrosine kinase 3, and VEGFR. The kinases targeted and inhibited by sorafenib and sunitinib directly and indirectly regulate tumor growth, survival, and angiogenesis, and this might be expected to result in broad antitumor efficacy. Sorafenib and sunitinib have been approved by the U.S. Food and Drug Administration for the treatment of metastatic renal cell carcinoma; sunitinib has also been approved for the treatment of gastrointestinal stromal tumors. Their mechanism of action, preclinical data, and phase II studies suggest efficacy in the treatment of advanced NSCLC.

Treatment of small cell lung cancer in the elderly.

Small cell lung cancer (SCLC) accounts for approximately 20% of lung carcinomas. Chemotherapy is the cornerstone of treatment for SCLC. In limited disease, the median survival time is about 12-16 months, with a 4%-5% long-term survival rate; in extensive disease the median survival time is 7-11 months. More than 50% of lung cancer patients are diagnosed when they are over the age of 65, and about 30% are over 70. Elderly patients tolerate chemotherapy poorly compared with their younger counterparts, because of age-related progressive reductions in organ function and comorbidities. The standard therapy for limited disease is combined chemoradiotherapy, followed by prophylactic brain irradiation for patients achieving complete responses. In the elderly, the addition of radiotherapy to chemotherapy must be carefully evaluated, considering the slight survival benefit and potential for substantial toxicity incurred with this treatment. The best approach is to design clinical trials that specifically include geriatric assessment to develop active and well-tolerated chemotherapy regimens for elderly SCLC patients. Survival improvement for SCLC patients requires a better understanding of tumor biology and the subsequent development of novel therapeutic strategies. Several targeted agents have been introduced into clinical trials in SCLC, but a minority of these new agents offers a promise of improved outcomes, and negative results are reported more commonly than positive ones. This review focuses on the main issues in the treatment of elderly SCLC patients.

Screening for lung cancer: New horizons?

Lung cancer remains the leading cause of cancer-related deaths in the world. At present, the only high rate of cure therapy is surgical resection at early stage of disease. Early detection could potentially decrease lung cancer mortality suggesting that this cancer should be a good candidate for screening. Results of trials involving chest X-ray, sputum cytology and low-dose computed tomography (CT) are discussed here. The latter tool offers advantages over chest X-ray, but final results from controlled well conducted trials are necessary before the real utility of CT mass screening can be determined. Further approaches to secondary prevention such as screening with positron emission tomography (PET), autofluorescence bronchoscopy and biomarkers hold great promise for the future.

The role of targeted therapy in non-small cell lung cancer.

The therapy of non-small cell lung cancer (NSCLC) has reached a plateau in improving patient survival, with overall disappointing results. Thus, clinical research for new treatment strategies is warranted. Advances in the singling out molecular targets for NSCLC treatment has granted the development of several new biological agents. In the present paper we describe the main clinical data currently available on targeted agents in the treatment of NSCLC, focusing on epidermal growth factor receptor family inhibitors, angiogenesis inhibitors, signal transduction inhibitors, eicosanoid pathway inhibitors, vaccines and gene therapy. Several targeted agents have been introduced into clinical trials in NSCLC, mainly in advanced disease, with the first phase III study results being recently made available. To date, few of these new agents can offer hope of a substantial impact on the natural history of NSCLC, and negative results are more commonly reported than positive ones. Nevertheless, clinically-meaningful advances have already been achieved in chemotherapy refractory advanced NSCLC patients, with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, representing a further chance of tumor control and symptom palliation. Moreover, important lessons can be learned from this first generation of clinical trials.