The current review is relevant because despite significant progress in oncology, a large proportion of patients with cancer still experience morbidity and symptoms, resulting from the cancer and/or ...its treatment.
The main theme concerns the definition of excellence of Supportive Care centers based on the indications of the Multinational Association Supportive Care Cancer (MASCC) because there are no data in literature on this topic.
Supportive care centers provide assistance to cancer patients suffering for anticancer treatments-related adverse effects. This leads to patient management with immediate evaluation and treatment of symptoms and therefore with improvement of quality of life and survival. In addition, there is less use of emergency room and hospitalizations with consequent savings of resources. According to MASCC evaluation criteria, some types of centers could be excellent in supportive care in cancer. Size, number of treated patients, or academic presence are not mandatory for the certification of excellence. However, centrality of patient and assessment of patient's needs, dedicated organizational models to evaluate and treat the adverse effects of anticancer treatments, dedicated activity and multidisciplinary staff, teaching programs, and adherence to guidelines are milestones for good clinical practices and consequently the centers that practice them represent the excellence in supportive care in cancer.
EGFR-positive Non-small Cell Lung Cancer (NSCLC) is a dynamic entity and tumor progression and resistance to tyrosine kinase inhibitors (TKIs) arise from the accumulation, over time and across ...different disease sites, of subclonal genetic mutations. For instance, the occurrence of EGFR T790M is associated with resistance to gefitinib, erlotinib, and afatinib, while EGFR C797S causes osimertinib to lose activity. Sensitive technologies as radiomics and liquid biopsy have great potential to monitor tumor heterogeneity since they are both minimally invasive, easy to perform, and can be repeated over patient's follow-up, enabling the extraction of valuable information. Yet, to date, there are no reported cases associating liquid biopsy and radiomics during treatment.
In this case series, seven patients with metastatic EGFR-positive NSCLC have been monitored during target therapy. Plasma-derived cell free DNA (cfDNA) was analyzed by a digital droplet PCR (ddPCR), while radiomic analyses were performed using the validated LifeX® software on computed tomography (CT)-images. The dynamics of EGFR mutations in cfDNA was compared with that of radiomic features. Then, for each EGFR mutation, a radiomic signature was defines as the sum of the most predictive features, weighted by their corresponding regression coefficients for the least absolute shrinkage and selection operator (LASSO) model. The receiver operating characteristic (ROC) curves were computed to estimate their diagnostic performance. The signatures achieved promising performance on predicting the presence of EGFR mutations (R
= 0.447, p <0.001 EGFR activating mutations R
= 0.301, p = 0.003 for T790M; and R
= 0.354, p = 0.001 for activating plus resistance mutations), confirmed by ROC analysis.
To our knowledge, these are the first cases to highlight a potentially promising strategy to detect clonal heterogeneity and ultimately identify patients at risk of progression during treatment. Together, radiomics and liquid biopsy could detect the appearance of new mutations and therefore suggest new therapeutic management.
The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; ...therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10
) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk.
The treatment of brain tumors and neurodegenerative diseases, represents an ongoing challenge. In Central Nervous System (CNS) the achievement of therapeutic concentration of chemical agents is ...complicated by the presence of distinct set of efflux proteins, such as ATP-Binding Cassette (ABC) transporters localized on the Blood-Brain Barrier (BBB). The activity of ABC transporters seems to be a common mechanism that underlies the poor response of CNS diseases to therapies. The molecular characterization of Breast Cancer Resistance Protein (BCRP/ABCG2), as an ABC transporter conferring multidrug resistance (MDR), has stimulated many studies to investigate its activity on the BBB, its involvement in physiology and CNS diseases and its role in limiting the delivery of drugs in CNS. In this review, we highlight the activity and localization of BCRP on the BBB and the action that this efflux pump has on many conventional drugs or latest generation molecules used for the treatment of CNS tumors and other neurodegenerative diseases.
Despite being long lived, anthracyclines remain the "evergreen" drugs in clinical practice of oncology, showing a potent effect in inhibiting cell growth in many types of tumors, including brain ...neoplasms. Unfortunately, they suffer from a poor penetration into the brain when intravenously administered due to multidrug resistance mechanism, which hampers their delivery across the blood brain barrier. In this paper, we summarize the current literature on the role of anthracyclines in cancer therapy and highlight recent efforts on 1) development of tumor cell resistance to anthracyclines and 2) the new approaches to brain drug delivery across the blood brain barrier.
Introduction: Cardiac rhabdomyomas represent a frequent manifestation of tuberous sclerosis. Tumor growth, mainly prenatally, can result in intrauterine fetal or neonatal deaths in almost 10% of ...patients. Case Report: We treated 3 consecutive infants aged less than 12 months with sirolimus, an oral mTOR inhibitor. All patients achieved significant reductions in cardiac rhabdomyomas. A complete response was documented in 2 patients, while a partial response with tumor debulking greater than 50% was seen in the other one. The median time to best cardiac response was 1.9 months in all patients, and 3.3 months in those with complete response. The side effects profile was acceptable. Conclusion: Sirolimus may have a significant role in promoting natural regression of cardiac rhabdomyomas. Prospective clinical trials are needed.
The incidence of gemcitabine-induced hemolytic uremic syndrome has already been described in adults. Several approaches have been employed in the treatment of gemcitabine-induced hemolytic uremic ...syndrome with different outcomes. One of the most promising agents is eculizumab, which is a monoclonal antibody directed against C5 complement protein.
We reported the case of a 3-year-old white boy with medulloblastoma who underwent high-dose chemotherapy and craniospinal irradiation. Afterwards he started maintenance chemotherapy with gemcitabine and oxaliplatin. After five courses he presented a progressive clinical worsening, which resulted in a systemic thrombotic microangiopathy. Initially he was treated with rituximab without clinical improvement. Therefore he started therapy with repeated cycles of eculizumab. After seven infusions he showed a gradual improvement and finally a complete remission of gemcitabine-induced hemolytic uremic syndrome.
Eculizumab prevents serious complement-mediated vascular damage for chemotherapy-induced thrombotic microangiopathy in pediatric cases.
Aim of this review is to encourage and involve more doctors to take care of supportive care in cancer patients and to become centers of excellence.
In 2019, MASCC initiated a certification program to ...recognize oncology centers that demonstrate best practices in supportive cancer care but literature on how to become MASCC-designated center of Excellence in Supportive Care in Cancer is scarce and will be bulleted.
Becoming centers of excellence means not only the recognition of the clinical and managerial requirements to provide good supportive care but also the creation of a network of centers to participate in multicenter scientific projects and thus improve knowledge in the field of supportive care in cancer patients.
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