Treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors. Next-generation ...sequencing (NGS) allows the assessment in a single analysis of a large number of gene alterations and might provide important predictive and prognostic information.
In the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line FOLFIRI plus cetuximab. Tumor samples (182/340, 53.5%) were assessed by NGS to search for mutations in 22 genes involved in colon cancer.
Objective responses in the NGS cohort were observed in 104/182 patients overall response rate (ORR) 57.1%; 95% confidence interval (95% CI) 52% to 66.4% with a median progression-free survival (mPFS) of 9.8 (95% CI 8.7–11.5) months. NGS analysis was successfully completed in all 182 samples. One or more gene mutations (up to five) were detected in 124/182 (68.1%) tumors within 14/22 genes for a total of 206 mutations. KRAS exon 2 mutations were identified in 29/182 (15.9%) samples, defined as wild type by local laboratory assessment. Frequently mutated genes were: TP53 (39.6%), KRAS exons 3/4 (8.8%), NRAS exons 2/3 (7.1%), PIK3CA exons 9/20 (13.2%), BRAF (8.2%). FOLFIRI plus cetuximab treatment determined ORR of 62.0% (95% CI 55.5% to 74.6%) with mPFS of 11.1 (95% CI 9.2–12.8) months in patients with KRAS and NRAS wild-type tumors. Conversely, ORR was 46.6% (95% CI 39.9–57.5%) with mPFS of 8.9 (95% CI 7.4–9.6) months in patients with KRAS or NRAS mutations. Similarly, the subgroup of patients carrying KRAS, NRAS, BRAF, or PIK3CA mutations showed a worse outcome, although this might be due to a prognostic effect.
This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Internet-enabled technologies are becoming more widespread; users are constantly connected to the network in every place and daily activity. Access to transportation-related features—mobile payment ...systems, Global Positioning System connections, real-time public transit timetables or traffic congestion information, and so on—is easy. This access results in new ways to plan mobility. In the innovative mobility systems implemented and developed with these technologies, the new real-time capabilities of dynamic ridesharing, an extended version of traditional ridesharing, can play a key role if the relevant performance is improved. In other words, although ridesharing is not a new idea, recent technological advances should increase its popularity. In this paper, a proposed ridesharing system considers the interactions between drivers or riders and the system manager and the interactions between drivers and riders. The positions and speeds of the shared vehicles and the traffic flows in which such vehicles travel are omitted. To optimize the performance of the ridesharing system, a discrete event, dynamic pickup and delivery model that represents the considered dynamics and an optimal matching problem that optimally allocates an empty seat in a vehicle to a rider are proposed. The dynamic model represents the behavior of the ridesharing system and computes the relevant performance; the optimization problem finds the best match and path in the considered transportation network to minimize the difference between the desired departure and arrival times. In this paper, after the introduction of the ridesharing model, the discussion of the solution to the optimal matching problem, a simulation model is described. A real world case study is then presented and discussed.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
An urban network of signalized intersections can be suitably modeled as a hybrid system, in which the vehicle flow behavior is described by means of a time-driven model and the traffic light dynamics ...are represented by a discrete event model. In this paper, a model of such a network via hybrid Petri nets is used to state and solve the problem of coordinating several traffic lights with the aim of improving the performance of some classes of special vehicles, i.e., public and emergency vehicles. The proposed model has been validated using real traffic data relevant to the city of Torino, Italy. Some relevant experimental results are reported and discussed.
Background
Breast cancer (BC) is the most common cancer among women worldwide. It has been estimated that approximately 12–20 % of patients will develop liver metastases from breast cancer (BCLM) and ...that in approximately 5 % of cases the liver is the only metastatic site. Patients with isolated BCLM have the poorest prognosis with a median survival ranging from 19 to 26 months.
Methods
A total of 26 women with isolated BCLM and without any sign of disease progression after a cycle of chemotherapy were retrospectively reviewed. Women were treated with hepatic resection (HR) for unilobar disease or surgical “open” RFA for bilobar disease. Data were collected on either original BC or BCLM and from patients follow-up.
Results
Overall survival from BC diagnosis was 47.69 ± 22.25 months (range 33–84, median 45.5 months); it was 52.25 ± 14.57 months (range 33–84, median 48.5 months) for the HR patients and 43.79 ± 27.14 months (range 9–101, median 39 months) for the RFA patients. Overall survival from BCLM treatment was 21.12 ± 12.78 months (range 9–64, median 15.5 months); in detail it was 29.42 ± 14.53 months (range 12–64, median 29.5 months) for the resected patients and 14 ± 4.45 months (range 9–24, median 13.5 months) for patients treated by RFA with a strongly significant survival difference for operated patients (
p
= 0.001). Overall disease-free survival from BCLM was 15.96 ± 13.16 months (range 3–64, median 12 months), disease-free survival for resected patients was 23.22 ± 16.2 months (range 8–64, median 18.5 months), and for patients treated by RFA was 9.64 ± 4.22 months (range 3–18, median 9 months; Fig.
1
). Overall 1, 2, and 5 years (actuarial) survival was respectively 80.7, 57, and 31 %. Given in details for the two groups, they were respectively 100, 66.6 and 34 % (actuarial) for the resected group patients and 64.2, 21.4, and 11.5 % (actuarial) for the RFA patients.
Fig. 1
Kaplan-Meier analysis of survival after BC and BCLM treatment. GROUP 1 = resection; GROUP 2 = RFA. Overall survival from breast cancer treatment (months)
p
= 0.082 ns. Overall survival from BCLM treatment (months)
p
= 0.001
Conclusions
Aggressive treatment on isolated BCLM may improve survival for these patients
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EMUNI, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, SBNM, UL, UM, UPUK
Purpose
Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor ...receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting.
Methods
We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%).
Results
Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95%CI: 8.7–52.8). Tumour response, PFS and OS decreased proportionally in later lines.
Conclusion
This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy ...at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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