Concomitant Treatment for Brain Metastases in Non-Small Cell Lung Cancer Patients: Our Clinical Experience
Pages 23-28
S. Simonida Crvenkova and Maja Popova

DOI: http://dx.doi.org/10.6000/1929-2279.2016.05.01.5

Published: 29 January2016

Abstract: Purpose: Aim of this study was to evaluate tumor response, Quality of life (QoL) and median survival of concomitant chemotherapy (P/E) protocol with WBRT (whole brain radiotherapy) followed by P/E protocol until progression or appearance of serious adverse effects in NSCLC patients with multiple brain metastases.

Methods: From December 2012 to April 2014, 12 patients were enrolled in this study. All of the patients received previous treatments. Selected patients had multiple brain metastases detected on CT and/or MRI, and the brain is only one site of disease dissemination and patients were at younger age.

External beam radiotherapy was administered with two lateral opposed fields. Concurrently with WBRT, patients received P/E protocol and after 4 weeks, followed by P/E protocol repeated on 21 days until progression or appearance of serious adverse effects. Tumor response was assessed according to RECIST criteria. Assessment of QoL was performed by patients’ subjective answers, subjective improvement in emesis, ataxia, headache and seizures and without subjective improvement. Adverse effects were performed according to WHO criteria. Overall survival was analyzed from the beginning of the concomitant treatment until death or patient’s last control.

Results: Common adverse events were neurotoxicity and hematology toxicity according to WHO criteria. No patient was withdrawn from the study because of the adverse events. All patients reported subjective improvements. Overall median survival was 7.5 months (95% CI 6.32-8.73).

Conclusions: WBRT plus chemotherapy can improve the efficacy and QoL in NSCLC patients, because of synergistic effect and current evidence that the blood-brain barrier is damaged in patients with BM. Considering our clinical results, we recommend this treatment as safe and effective for selected NSCLC patients.

Keywords: Concomitant chemotherapy and WBRT, NSCLC patients, brain metastases.

Molecular Technologies in Gynecologic Oncology
Pages 195-226
Ciro Comparetto and Franco Borruto

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.04.8

Published: 10 December 2015

Abstract: In recent years, the application of molecular biological techniques to the diagnosis and treatment of cancer has proved successful. In this kind of pathologies, molecular diagnosis is of fundamental importance as it allows identification at a pre-symptomatic stage, and then in the early phase, of the subjects in which cancer disease is developing. Molecular diagnosis of tumors by deoxy-ribonucleic acid (DNA) analysis is conducted on biological samples such as urine, feces, sputum, vaginal swab, and blood, searching and identifying in the various samples for the presence of cell carriers of an altered genetic information. The sensitivity of this kind of analysis is so high as to be very reliable even in the presence in the sample of a few tumor cells, level not reachable through the traditional “tumor markers”. The achievement of a facilitated early diagnosis of the tumor and, consequently, through the organization of specific therapeutic interventions, the prevention of the invasiveness of the pathology, allow to insert this kind of analysis among the most important investigations in the field of cancer prevention. Molecular oncology examinations have targeted the mutational study of the most involved genes in the onset of hereditary and/or family cancers such as breast, ovary, colon, melanoma, stomach, thyroid, etc. In addition, given the growing focus on the molecular mechanisms underlying the individual response to conventional chemotherapeutic drugs and molecular targeted agents responsible for drug resistance, pharmacogenetics exams have been added to those of molecular oncology.

Some genes, when altered and/or mutated, can cause the development of tumors. In some types of cancer, the mutation may affect only somatic cells: in this case, the development will manifest itself only in the subject carrier of the mutation. Otherwise, if the mutation affects germ cells genes, it may occur the possibility to convey to children a susceptibility to the development of tumors. In fact, a significant proportion of cancers are hereditary. For example, it is estimated that about 7% of breast cancers, 10% of ovarian cancers, and about 5-10% of colorectal cancers, are caused by recurrent mutations at specific genes level. The early detection of cancer, with the ability to identify individuals at risk of developing the disease, is now the best way to reduce mortality from it. Determining whether a person has a mutation in a gene involved in neoplastic transformation that predisposes to the development of cancer (susceptibility or genetic predisposition) can significantly decrease its incidence and mortality. For example, as a result of in-depth studies of families at risk, it has been estimated that women who have inherited mutations in breast cancer genes (BRCA1 or BRCA2) are likely to develop breast cancer in 87% of cases, compared with 10% of non-bearers. This probability falls to 44-60% in the case of ovarian cancer, compared with 1% probability of not carriers. In this area, basic research has been developed with the aim of contributing to the study of the molecular mechanisms of oncogenesis, which generally has multistage character, with an initial immortalization and cell transformation and subsequent tumor progression. In this regard, studies at the molecular and functional level have been focused on models of different types of cancer, e.g. melanoma. In parallel, it has been studied the possible oncogenetic role of certain families of genes that have a functional role in embryogenesis, and in general in cell proliferation/differentiation, e.g. homeotic (HOX) genes. The gene expression profiles of purified cancer cells can be evaluated by microarray technique, comparing them with those of normal cells: comparative analysis, based on specific software, allows the identification of genes selectively modulated in the genetic program of tumor cells, in particular of genes specifically involved in the onset and progression of tumors.

The modern goal of cancer therapy is to eliminate the disease by minimizing trauma and paying attention to the quality of life (QOL). With the passing of time, there has been a change of therapeutic paradigms and we have gone from the objective of maximum tolerable treatment to that of minimum effective treatment. This clinical imperative has its foundation in the quick transfer of biological knowledges to the care, integrating molecular informations with the development of new treatment methods. Especially for a delicate operation, even psychologically, such as that for breast cancer. In this setting, we have focused particularly on the technique of sentinel lymph node, demonstrating the possibility to avoid the treatment of the axilla in patients at low risk of recurrence. The term “molecular targeted therapy” is used to refer to agents that target specific pathways activated in the processes of growth, survival, invasion, and metastasis of cancer cells and in tumor neo-angiogenesis. The large and perhaps excessive optimism, caused by the gradual deepening of the knowledges of these mechanisms, has received a further boost by the arrival on the therapeutic scene of imatinib and other drugs belonging to the class of targeted biomolecular agents, including some monoclonal antibodies (McAb) such as trastuzumab, rituximab, cetuximab, and bevacizumab, and some small molecules, already entered clinical practice. But the question we must ask is whether that enthusiasm is justified and supported by scientifically strong and clinically proven data. The difficulties encountered in the research and development of new truly effective molecules and the disappointing results obtained in the early life of some of these agents and, not least, the high costs of treatments must lead to greater caution. The medical oncologist has the inescapable duty to possess sufficient culture to be able to properly use these new therapies in his diagnosis and treatment decision-making.

A Guide for Pain Management in Developing Nations: The Diagnosis and Assessment of Pain in Cancer Patients
Pages 29-44
Joseph V. Pergolizzi, Gianpietro Zampogna, Robert Taylor, Marixa Guerrero, Juan Quillermo Santacruz and Robert B. Raffa

DOI: http://dx.doi.org/10.6000/1929-2279.2016.05.01.6

Published: 29 January2016

Abstract: The fundamental approach to cancer patients with pain is to identify the pain sites, and describe, quantify, and categorize the pain by type at each site. There are many validated tools to serve the clinician in these efforts, particularly for pain assessment. Multimechanistic pain syndromes are common in cancer patients. Cancer patients may experience nociceptive pain. They may also experience neuropathic pain due to chemotherapy-induced or cancer-related nerve damage. Analgesic choices must be guided by the pain mechanisms, nature, and severity of the pain, comorbid conditions, and patient characteristics. Long-acting opioid analgesics or fixed-clock dosing can eliminate end-of-dose analgesic gaps. The potential for opioid abuse is an important public health challenge but one that should not undermine the appropriate treatment of moderate to severe cancer pain. Abuse-deterrent opioid formulations can be useful. Care is needed for special populations of cancer patients dealing with pain, such as geriatric, pediatric, or obese patients. While morphine has long been the “gold standard” of oral opioid products, recent clinical trials suggest that oral hydrocodone and oral oxycodone may offer advantages over oral morphine. Patient adherence is crucial for adequate analgesia and patient education can promote adherence and manage expectations.

Keywords: Cancer pain, malignant pain, opioid analgesia, opioids, undertreatment of cancer pain, assessment of cancer pain.

Function Shapes Content: DNA-Methylation Marker Genes and their Impact for Molecular Mechanisms of Glioma
Pages 127-148
Lydia Hopp, Edith Willscher, Henry Löffler-Wirthand Hans Binder

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.04.1

Published: 26 November 2015

Abstract: Glioma is a clinically and biologically diverse disease. It challenges diagnosis and prognosis due to its molecular heterogeneity and diverse regimes of biological dysfunctions which are driven by genetic and epigenetic mechanisms. We discover the functional impact of sets of DNA methylation marker genes in the context of brain cancer subtypes as an exemplary approach how bioinformatics and particularly machine learning using self organizing maps (SOM) complements modern high-throughput genomic technologies. DNA methylation changes in gliomas comprise both, hyper- and hypomethylation in a subtype specific fashion. We compared pediatric (2 subtypes) and adult (4) glioblastoma and non-neoplastic brain. The functional impact of differential methylation marker sets is discovered in terms of gene set analysis which comprises a large collection of markers related to biological processes, literature data on gliomas and also chromatin states of the healthy brain. DNA methylation signature genes from alternative studies well agree with our signatures. SOM mapping of gene sets robustly identifies similarities between different marker sets even under conditions of noisy compositions. Mapping of previous sets of glioma markers reveals high redundancy and mixtures of subtypes in the reference cohorts. Consideration of the regulatory level of DNA methylation is inevitable for understanding cancer genesis and progression. It provides suited markers for diagnosis of glioma subtypes and disentangles tumor heterogeneity.

Keywords: Glioma, molecular subtypes, DNA methylation, gene regulation, bioinformatics.