Breast Sarcomas, Phyllodes Tumors, and Desmoid Tumors: Turning the Magnifying Glass on Rare and Aggressive Entities.

Breast sarcomas (BSs), phyllodes tumors (PTs), and desmoid tumors (DTs) are rare entities that arise from connective tissue. BSs can be classified as either primary or secondary, whether they develop de novo or after radiation exposure or lymphedema. PIK3CA seems to play an important common role in different BS. Malignant PTs show similar behavior to BSs, while DTs are locally aggressive but rarely metastasize. BSs usually present as unilateral, painless, rapidly growing masses with rare nodal involvement. The diagnosis should be based on magnetic resonance imaging and a core needle biopsy. Staging should comprise a chest computed tomography (CT) scan (except for benign PT and DT), while abdominal and pelvic CT scans and bone scans should be added in certain subtypes. The mainstay of treatment for localized BS is surgery, with margin goals that vary according to subtype. Radiotherapy and chemotherapy can be used as neoadjuvant or adjuvant approaches, but their use in these settings is not standard. Advanced BS should be treated with systemic therapy, consistent with recommendations for advanced soft tissue sarcomas of other topographies. Given the rarity and heterogeneity of these entities, multidisciplinary and multi-institutional collaboration and treatment at reference centers are critical.

Identification of biomarkers predictive of metastasis development in early-stage colorectal cancer using network-based regularization.

Colorectal cancer (CRC) is the third most common cancer and the second most deathly worldwide. It is a very heterogeneous disease that can develop via distinct pathways where metastasis is the primary cause of death. Therefore, it is crucial to understand the molecular mechanisms underlying metastasis. RNA-sequencing is an essential tool used for studying the transcriptional landscape. However, the high-dimensionality of gene expression data makes selecting novel metastatic biomarkers problematic. To distinguish early-stage CRC patients at risk of developing metastasis from those that are not, three types of binary classification approaches were used: (1) classification methods (decision trees, linear and radial kernel support vector machines, logistic regression, and random forest) using differentially expressed genes (DEGs) as input features; (2) regularized logistic regression based on the Elastic Net penalty and the proposed iTwiner-a network-based regularizer accounting for gene correlation information; and (3) classification methods based on the genes pre-selected using regularized logistic regression. Classifiers using the DEGs as features showed similar results, with random forest showing the highest accuracy. Using regularized logistic regression on the full dataset yielded no improvement in the methods' accuracy. Further classification using the pre-selected genes found by different penalty factors, instead of the DEGs, significantly improved the accuracy of the binary classifiers. Moreover, the use of network-based correlation information (iTwiner) for gene selection produced the best classification results and the identification of more stable and robust gene sets. Some are known to be tumor suppressor genes (OPCML-IT2), to be related to resistance to cancer therapies (RAC1P3), or to be involved in several cancer processes such as genome stability (XRCC6P2), tumor growth and metastasis (MIR602) and regulation of gene transcription (NME2P2). We show that the classification of CRC patients based on pre-selected features by regularized logistic regression is a valuable alternative to using DEGs, significantly increasing the models' predictive performance. Moreover, the use of correlation-based penalization for biomarker selection stands as a promising strategy for predicting patients' groups based on RNA-seq data.

Immunotherapy in Metastatic Mucosal Melanoma with Disseminated Intravascular Coagulation: A Case of Success.

Mucosal melanoma accounts for 1% of all melanomas. It is more aggressive than cutaneous melanoma, and local excision provides the best disease-free survival. The vast majority of patients eventually develop metastases, with a metastatic pattern independent of the primary tumor site. While studies show that BRAF and KIT inhibitors have a role in the management of these patients, the actual treatment focus is on immunotherapy. Herein is described the case of a 79-year-old woman with metastatic mucosal melanoma and bone marrow infiltration causing disseminated intravascular coagulation, who was treated with an immunotherapy combination (anti-CTLA-4 and anti-PD-1 antibodies), achieving complete disease remission. This is the third case of melanoma with disseminated intravascular coagulation at presentation and the second case treated with immunotherapy in the literature, but the only one achieving disease remission.

BRAF L597K mutation: an opportunity to treat.

The outcomes of patients with metastatic melanoma (MM) have significantly improved after the introduction of BRAF-specific inhibitors. Herein is reported a patient with MM and non-V600-BRAF mutation who responded to iBRAF/iMEK therapy. In July 2014, a 63-year-old man presented with a 4.1mm-thick V600E-BRAF wild type melanoma on the back. Metastases were identified in one sentinel node and two of 11 subsequently excised lymph nodes, with no signs of distant metastatic disease. In September 2017, lung metastasis was observed and pembrolizumab was started. Progressive disease was apparent at cycle 10 and therapy was switched to ipilimumab. After four cycles, an asymmetric response was observed. In November 2017, next generation sequencing genomic profiling disclosed a rare L597K-BRAF mutation and vemurafenib plus cobimetinib therapy was initiated in January 2018. Seven days after treatment start, a remarkable clinical improvement was observed. In April 2018, the patient achieved partial response, which was sustained until October 2018. Cases of patients with non-V600-BRAF mutations responding to iBRAF/iMEK therapy have been reported over the last years. To the best of our knowledge, this is the first case reporting response to combined iBRAF/iMEK therapy in a patient with metastatic melanoma harboring L597K mutation.

Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma.

AIM: Evaluate pretreatment hemoglobin values as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy. BACKGROUND: Anemia is one of the most prevalent laboratory abnormalities in oncological disease. It leads to a decrease in cellular oxygen supply, altering radiosensitivity of tumor cells and compromising therapeutic outcomes. MATERIALS AND METHODS: Retrospective evaluation of patients with HNSCC treated with cCRT. Primary and secondary endpoint was to evaluate the correlation of Hb levels (≥12.5 g/dL or <12.5 g/dL) at the beginning of cCRT with overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: A total of 108 patients were identified. With a median follow-up of 16.10 months median OS was 59.70 months for Hb ≥12.5 g/dL vs. 14.13 months for Hb <12.5 g/dL (p = 0.004). PFS was 12.29 months for Hb ≥12.5 g/dL and 1.68 months for Hb <12.5 g/dL (p = 0.016). CONCLUSIONS: In this analysis, Hb ≥12.5 g/dL correlated with significantly better OS and PFS. Further studies are needed to validate these findings.

Pregnancy After Breast Cancer in Patients With Germline BRCA Mutations.

PURPOSE: Young women with germline BRCA mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients with BRCA mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline BRCA mutations. PATIENTS AND METHODS: This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline BRCA mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors. RESULTS: Of 1,252 patients with germline BRCA mutations (BRCA1, 811 patients; BRCA2, 430 patients; BRCA1/2, 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio [HR], 0.87; 95% CI, 0.61 to 1.23; P = .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56; P = .66) were observed between the pregnancy and nonpregnancy cohorts. CONCLUSION: Pregnancy after breast cancer in patients with germline BRCA mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility.

Low Density In-Medium Effects on Light Clusters from Heavy-Ion Data.

The modification of the ground state properties of light atomic nuclei in the nuclear and stellar medium is addressed, using chemical equilibrium constants evaluated from a new analysis of the intermediate energy heavy-ion (Xe+Sn) collision data measured by the INDRA Collaboration. Three different reactions are considered, mainly differing by the isotopic content of the emission source. The thermodynamic conditions of the data samples are extracted from the measured multiplicities allowing for a parametrization of the in-medium modification, determined with the single hypothesis that the different nuclear species in a given sample correspond to a unique common value for the density of the expanding source. We show that this correction, which was not considered in previous analyses of chemical constants from heavy-ion collisions, is necessary, since the observables of the analyzed systems show strong deviations from the expected results for an ideal gas of free clusters. This dataset is further compared to a relativistic mean-field model, and seen to be reasonably compatible with a universal correction of the attractive σ-meson coupling.

Cetuximab versus bevacizumab in metastatic colorectal cancer: a comparative effectiveness study.

PURPOSE: Uncertainty exists regarding comparative effectiveness of cetuximab versus bevacizumab in metastatic colorectal cancer (mCRC). We conducted a retrospective head-to-head multi-cohort study comparing clinical outcomes from both antibodies METHODS: Cohorts were defined by treatment line and subgroups by (K)RAS status and tumour sidedness. Among other outcomes, we estimated and compared response rates, progression-free (PFS) and overall survival (OS). RESULTS: Between January 2010 and April 2018, 311 patients were included. Except for (K)RAS mutation status, baseline characteristics were balanced across treatment groups. In the full analysis of first and second-line cohorts, PFS (first-line: HR = 0.85; 95% CI 0.64 to 1.13; P = 0.26; second-line: HR = 1.16; 95% CI 0.74 to 1.83; P = 0.51) and OS (first-line: HR = 0.83; 95% CI 0.61 to 1.15; P = 0.26; second-line: HR = 0.88; 95% CI 0.56 to 1.38; P = 0.58) were similar between bevacizumab and cetuximab arms. In subgroup analyses of first-line therapy, we found a survival difference favouring bevacizumab in right-sided tumours (PFS: HR = 0.52; 95% CI 0.29 to 0.93; P = 0.025; OS: HR = 0.60; 95% CI 0.32 to 1.12; P = 0.11), but not in left-sided (HR = 1.04; 95% CI 0.75 to 1.46; P = 0.81; OS: HR = 0.94; 95% CI 0.65 to 1.36; P = 0.74), or (K)RAS wild-type tumours (PFS: HR = 0.91; 95% CI 0.60 to 1.40; P = 0.67; OS: HR = 0.79; 95% CI 0.50 to 1.25; P = 0.31). Response rates were similar across treatment groups, except for the subgroup of patients bearing right-sided primaries, where bevacizumab performed substantially better. CONCLUSION: This study provides evidence suggesting bevacizumab and cetuximab lead to similar effectiveness outcomes in mCRC, except for right-sided tumours, where cetuximab seemed to show considerably poorer outcomes. Further research is needed to confirm these results.

Patient-reported outcomes and health-related quality of life for cetuximab versus bevacizumab in metastatic colorectal cancer: a prospective cohort study.

PURPOSE: Uncertainty exists regarding Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) of patients with metastatic colorectal cancer (mCRC) treated with cetuximab or bevacizumab. We conducted a prospective cohort study comparing PROs and HRQoL from both therapies. METHODS: We assessed PROs and HRQoL from patients treated with cetuximab or bevacizumab using QLQ-C30 and QLQ-CR29 questionnaires at three sequential time points, including baseline. Global Health Status (GHS), functional and symptom scales, and Overall Treatment Utility (derived from clinical and patient-reported outcomes) were compared for the two treatment strategies. RESULTS: Between January 2017 and April 2018, 44 patients were allocated to cetuximab (n = 19) or bevacizumab (n = 25). Except for RAS mutation status, patient baseline characteristics were generally well balanced across treatment groups. A higher proportion of patients experienced a deterioration in GHS (≥ 10%) in cetuximab arm - 53.8% (95% CI 25.1-80.8%) at 6 weeks and 66.7% (95% CI 29.9-92.5%) at 12 weeks-comparing to bevacizumab cohort: 18.2% (95% CI 5.2-40.3%) at 6 weeks and 12.5% (95% CI:1.6-38.3%) at 12 weeks. Treatment utility rates at 6 and 12 weeks were, respectively, 88.6% and 69.8% for bevacizumab, compared to 49% and 19.1% for cetuximab (p = 0.004), a difference confirmed in subset analyses. CONCLUSIONS: In patients with mCRC, cetuximab-containing regimens led to a progressive negative impact on PROs and global HRQoL, when compared to baseline and bevacizumab. Future research is needed to confirm these results. Our findings demonstrate the value of PROs when assessing comparative effectiveness of different treatment regimens.

Radionuclides in oncology clinical practice - review of the literature.

Radionuclide therapy is a type of targeted therapy that can be useful in the treatment of several malignant tumors. Compared with other forms of systemic therapy used in cancer - including chemotherapy - it has the advantage of sparing biological structures adjacent to the tumor cells. This treatment modality has registered significant advances since its first use for the treatment of tuberculous skin lesions in the 1900s. This paper reviews the characteristics and clinical applications of therapeutic radionuclides commonly used in the oncology clinical practice, and discusses future potential applications.

Triplet (FOLFOXIRI) versus doublet (FOLFOX or FOLFIRI) backbone chemotherapy as first-line treatment of metastatic colorectal cancer: A systematic review and meta-analysis.

Uncertainty exists regarding the comparative effectiveness of triplet chemotherapy (FOLFOXIRI) as backbone first-line chemotherapy for metastatic colorectal cancer (mCRC). We conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) comparing triplet versus doublet chemotherapy (FOLFOX or FOLFIRI) as first-line therapy in mCRC. Methods and reporting followed PRISMA and SAMPL guidelines. Eight RCTs were included, comprising 1732 patients. In pooled analysis, FOLFOXIRI was associated with improvements in efficacy outcomes, notably with a 25% survival increase (95%CI: 10-37%). FOLFOXIRI was also associated with increased toxicity, with a non-significant 25% increase in the risk of patients experiencing grade ≥3 adverse events (95% CI: -3 to 61%) and with a 1.83 (95% CI: 1.62-2.07) increase in the rate ratio of grade ≥3 adverse events. Moderate quality evidence suggests that first-line FOLFOXIRI provides clinically meaningful efficacy benefits in this setting, at the expense of increased toxicity. Further research is warranted to better characterize safety and to evaluate the most beneficial combination with targeted agents.

Exploring the nuclear pasta phase in core-collapse supernova matter.

The core-collapse supernova phenomenon, one of the most explosive events in the Universe, presents a challenge to theoretical astrophysics. Of the large variety of forms of matter present in core-collapse supernova, we focus on the transitional region between homogeneous (uniform) and inhomogeneous (pasta) phases. A three-dimensional, finite temperature Skyrme-Hartree-Fock (3D-SHF)+BCS calculation yields, for the first time fully self-consistently, the critical density and temperature of both the onset of the pasta in inhomogeneous matter, consisting of neutron-rich heavy nuclei and a free neutron and electron gas, and its dissolution to a homogeneous neutron, proton, and electron liquid. We also identify density regions for different pasta formations between the two limits. We employ four different forms of the Skyrme interaction, SkM*, SLy4, NRAPR, and SQMC700 and find subtle variations in the low density and high density transitions into and out of the pasta phase. One new stable pasta shape has been identified, in addition to the classic ones, on the grid of densities and temperatures used in this work. Our results are critically compared to recent calculations of pasta formation in the quantum molecular dynamics approach and Thomas-Fermi and coexisting phase approximations to relativistic mean-field models.