Metronomic Oral Vinorelbine: An Alternative Schedule in Elderly and Patients PS2 With Local/Advanced and Metastatic NSCLC Not Oncogene-addicted

The MILES and ELVIS studies showed that vinorelbine is one of the best options for elderly patients with advanced non-small-cell-lung cancer (NSCLC). Oral vinorelbine at standard schedule (60-80 mg/m2/weekly) has good activity in terms of response rates and progression-free survival. In recent years, a metronomic schedule of oral vinorelbine (40-50 mg/m2 three times a week, continuously) has been studied in phase II trials, especially in unfit and elderly patients. In the MOVE trial metronomic oral vinorelbine had a clinical benefit [partial response (PR)+stable disease (SD) >12 weeks] in 58.1% of patients with mild toxicity. On this basis, in 2017 we started a phase II study with metronomic oral vinorelbine in elderly (over 70 years) or unfit [Eastern Cooperative Oncology Group performance score (ECOG-PS) of 2] patients with locally/advanced and metastatic NSCLC. Primary aims were clinical benefit (PR+SD ≥6 months) and toxicity; secondary aims were progression-free survival and overall survival

Personalization of regorafenib treatment in metastatic gastrointestinal stromal tumours in real-life clinical practice

Background: Regorafenib (REG) has now been approved as the standard third-line therapy in metastatic gastrointestinal stromal tumour (GIST) patients at the recommended dose and schedule of 160 mg once daily for the first 3 weeks of each 4-week cycle. However, it has a relevant toxicity profile that mainly occurs within the first cycles of therapy, and dose and schedule adjustments are often required to reduce the frequency or severity of adverse events and to avoid early treatment discontinuation. To date, large amounts of data on the use of REG in metastatic GIST patients in daily clinical practice are not available, and we lack information about how this treatment personalization really affects the quality of life (QoL) of patients. The aim of the present retrospective study is to build a comprehensive picture of all alternative REG strategies adopted in daily clinical practice for use in metastatic GIST patients. Methods: Metastatic GIST patients treated with dose adjustment or alternative schedules of REG at seven reference Italian centres were retrospectively included. Results: For a total of 62 metastatic GIST patients, we confirmed that REG treatment adjustment is common in clinical practice and that it is very heterogeneous, with approximately 20 different strategies being adopted. Independent of which strategy is chosen, treatment personalization has led to a clinical benefit defined as complete or partial resolution of side effects in almost all patients, affecting the duration of REG treatment. Conclusions: The personalization of REG, even if it is heterogeneous, seems to be crucial to maximize the overall treatment duration

Regulation of microRNA using promising dietary phytochemicals: Possible preventive and treatment option of malignant mesothelioma

Malignant mesothelioma (MM) is a very aggressive, lethal cancer, and its incidence is increasing worldwide. Development of multi-drug resistance, therapy related side-effects, and disease recurrence after therapy are the major problems for the successful treatment of MM. Emerging evidence indicates that dietary phytochemicals can exert anti-cancer activities by regulating microRNA expression. Until now, only one dietary phytochemical (ursolic acid) has been reported to have MM microRNA regulatory ability. A large number of dietary phytochemicals still remain to be tested. In this paper, we have introduced some dietary phytochemicals (curcumin, epigallocatechin gallate, quercetin, genistein, pterostilbene, resveratrol, capsaicin, ellagic acid, benzyl isothiocyanate, phenethyl isothiocyanate, sulforaphane, indole-3-carbinol, 3,3'-diindolylmethane, diallyl disulphide, betulinic acid, and oleanolic acid) which have shown microRNA regulatory activities in various cancers and could regulate MM microRNAs. In addition to microRNA regulatory activities, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, phenethyl isothiocyanate, and sulforaphane have anti-mesothelioma potentials, and pterostilbene, capsaicin, ellagic acid, benzyl isothiocyanate, indole-3-carbinol, 3,3'-diindolylmethane, diallyl disulphide, betulinic acid, and oleanolic acid have potentials to inhibit cancer by regulating the expression of various genes which are also known to be aberrant in MM

Risk stratification systems for surgically treated localized primary Gastrointestinal Stromal Tumors (GIST). Review of literature and comparison of the three prognostic criteria: MSKCC Nomogramm, NIH-Fletcher and AFIP-Miettinen.

PURPOSE: The discovery of Imatinib mesylate (Gleevec®) has revolutionized the treatment of GIST, increasing disease-free survival (DFS) after complete surgical resection of a primary localized GIST and extending overall survival in metastatic disease. The definition of an accurate prognostic system is critical for the therapeutic decision making process. In literature, there are three main prognostic criteria F/NIH consensus, AFIP standards and modified NIH standards. In recent years were added various risk identification methods applying mathematical calculation model, including MSKCC risk nomogram, Rossi nomogram and Joensuu high Hotline Dengjun. Despite all these attempts, it seems that the recurrence risk probability still cannot be predicted accurately. The aim of our study was to assess and compare the real ability of these prognostic instruments in our single-centre clinical experience, and to define if the use of the MSKCC nomogram can bring benefits in the therapeutic decision. METHODS: All data regarding 37 GIST, who underwent surgical resection from 1996 to 2011 in our institution were retrospectively reviewed. We selected only primary GIST without metastatic disease who underwent a radical resection (R0) but no other therapy. The literature data concerning GISTs prognostication criteria were reviewed. All patients were classified according to the three prognostic criteria (NIH, AFIP and Nomogram MSKCC) and the three instruments were compared with the Kaplan-Meier method. Then we compared the three criteria for their c-index value and we assessed the performance of the nomogram with the calibration test. RESULTS: We observed 9 recurrences (24%) with an average time to relapse of 43 months; the median follow-up was 65 months. In the study selected sample occurred 5 relapses. The probability of relapsing after radical surgery was 7.9% (95% CI 0-17.3) at 2 years and 13.3% at 5 years (95% CI 0-26.4). The C-Index of the three risk assessment tools was 0.93 (95% CI 0.83-1) for the Nomogram at 5 years, 0.86 (95% CI 0.76-0.95) for the NIH risk criteria and 0.88 (95% CI 0.74-1) for the AFIP risk criteria. The calibration analysis of the nomogram showed an overestimating trend both at 2 and 5 years. CONCLUSION: MSKCC nomogram seems to perform better than NIH, NIH modified and AFIP in our sample and can be used in clinical practice to predict the risk of recurrence, being especially helpful for the therapeutic decision making since it is at the same time simple to use and accurate. As showed from calibration, MSKCC doesn't seem to neglect relapses, even though it is not impeccable in predicting the RFS. Among the 2 older criteria AFIP was more precise than NIH, but considering size in not linear way represented a limit in comparison with the MSKCC Nomogram. All the three risk assessement tools criteria considered are capable to predict recurrence in high-risk GISTs while they performed worse in those with lower risk. MSKCC nomogram main limit remains the not linear consideration of mitotic count

Night shift work and serum markers of bone turnover in male shift workers

: Night shift work is related to sleep disorders, disruption of circadian rhythm and low serum levels of vitamin D. It is known that all these conditions can adversely affect bone mass. The rate of bone turnover can be assessed through the measurement of molecules called bone turnover markers, including C-terminal telopeptide fragment of type I collagen (CTX) and procollagen type I N-terminal propeptide (P1NP). In this study, we evaluated the serum levels of CTX, P1NP and 25-Hydroxy Vitamin D in 82 male subjects (42 daytime workers and 40 night shift workers) to assess the possible risk of osteoporosis in male shift workers. Serum levels of CTX and P1NP were found to be higher in night shift workers than in daytime workers. No significant difference was found in vitamin D levels between night shift and daytime workers. The increased CTX and P1NP levels reveal a higher rate of bone turnover in night shift workers and thus a possible increased risk of osteoporosis in this category of workers compared with daytime workers. In view of this, our results highlight the importance of further studies investigating the bone health in male night shift workers

Can extremely low frequency magnetic field affect human sperm parameters and male fertility?

Exposure to extremely low frequency magnetic fields (ELF-MF) may have different effects on spermatozoa depending on the waveform, magnetic flux density, frequency of ELF-MF, and duration of exposure. In this study, we investigated the possible role of ELF-MF (50 Hz; 1 mT) exposure in altering sperm parameters. In this study we found that exposure to ELF-MF at the frequency of 50 Hz (1 mT) for two hours induces statistically significant alterations in progressive motility, morphology and reactive oxygen species (ROS) production of human sper-matozoa, suggesting a role of ELF-MF in altering reproductive function of spermatozoa. Our results represent an important discovery in the field since occupational exposure to the sine waveform 1 mT 50 Hz ELF-MF used in our study is possible in workplace. Moreover, these electromagnetic fields are product by many electronic de-vices and household appliances. Thus, alterations of progressive motility and morphology of spermatozoa would be important consequences of human exposures to ELF-MF

Prognostic impact of mismatch repair genes germline defects in colorectal cancer patients: are all mutations equal?

Background: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by germline mutations in MisMatch Repair (MMR) genes, particularly in MLH1, MSH2 and MSH6. Patients with LS seem to have a more favourable prognosis than those with sporadic CRC, although the prognostic impact of different mutation types is unknown. Aim of our study is to compare survival outcomes of different types of MMR mutations in patients with LS-related CRC. Methods: 302 CRC patients were prospectively selected on the basis of Amsterdam or Revised Bethesda criteria to undergo genetic testing: direct sequencing of DNA and MLPA were used to examine the entire MLH1, MSH2 and MSH6 coding sequence. Patients were classified as mutation-positive or negative according to the genetic testing result. Results: A deleterious MMR mutation was found in 38/302 patients. Median overall survival (OS) was significantly higher in mutation-positive vs mutation-negative patients (102.6 vs 77.7 months, HR:0.63, 95%CI:0.46-0.89, p = 0.0083). Different types of mutation were significantly related with OS: missense or splicing-site mutations were associated with better OS compared with rearrangement, frameshift or non-sense mutations (132.5 vs 82.5 months, HR:0.46, 95%CI:0.16-0.82, p = 0.0153). Conclusions: Our study confirms improved OS for LS-patients compared with mutation-negative CRC patients. In addition, not all mutations could be considered equal: the better prognosis in CRC patients with MMR pathogenic missense or splicing site mutation could be due to different functional activity of the encoded MMR protein. This matter should be investigated by use of functional assays in the future

A 50 Hz magnetic field influences the viability of breast cancer cells 96 h after exposure

The exposure of breast cancer to extremely low frequency magnetic fields (ELF-MFs) results in various biological responses. Some studies have suggested a possible cancer-enhancing effect, while others showed a possible therapeutic role. This study investigated the effects of in vitro exposure to 50 Hz ELF-MF for up to 24 h on the viability and cellular response of MDA-MB-231 and MCF-7 breast cancer cell lines and MCF-10A breast cell line