Validation of a prognostic score for hidden cancer in unprovoked venous thromboembolism

The usefulness of a diagnostic workup for occult cancer in patients with venous thromboembolism (VTE) is controversial. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to perform a nested case-control study to validate a prognostic score that identifies patients with unprovoked VTE at increased risk for cancer. We dichotomized patients as having low- (≤2 points) or high (≥3 points) risk for cancer, and tried to validate the score at 12 and 24 months. From January 2014 to October 2016, 11,695 VTE patients were recruited. Of these, 1,360 with unprovoked VTE (11.6%) were eligible for the study. At 12 months, 52 patients (3.8%; 95%CI: 2.9–5%) were diagnosed with cancer. Among 905 patients (67%) scoring ≤2 points, 22 (2.4%) had cancer. Among 455 scoring ≥3 points, 30 (6.6%) had cancer (hazard ratio 2.8; 95%CI 1.6–5; p<0.01). C-statistic was 0.63 (95%CI 0.55–0.71). At 24 months, 58 patients (4.3%; 95%CI: 3.3–5.5%) were diagnosed with cancer. Among 905 patients scoring ≤2 points, 26 (2.9%) had cancer. Among 455 patients scoring ≥3 points, 32 (7%) had cancer (hazard ratio 2.6; 95%CI 1.5–4.3; p<0.01). C-statistic was 0.61 (95%CI, 0.54–0.69). We validated our prognostic score at 12 and 24 months, although prospective cohort validation is needed. This may help to identify patients for whom more extensive screening workup may be required.Peer reviewe

Late toxicity for prostate cancer patients treated with hypofractionated helical tomotherapy

AimThe purpose of this study is to evaluate the long term tolerability of hypofractionated helical tomotherapy (HT) in localized prostate cancer patients.BackgroundPrevious hypofractionated schedules with conventional RT were associated with excessive toxicity, likely due to inadequate sophistication of treatment delivery. There are few data about late toxicity after HT.Materials and methodsWe evaluated 38 patients with primary adenocarcinoma of the prostate. There were 9 (24%), 15 (39%), and 14 (37%) patients with high, intermediate, and low risk, respectively. Patients were treated with hypofractionated HT from May 2008 to February 2011. Hypofractionation regimens included: 68.04Gy at 2.52Gy/fraction (N=25; 66%), 70Gy at 2.5Gy/fraction (N=4; 11%) and 70.2Gy at 2.6Gy/fraction (N=9; 23%). Late genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system.ResultsMedian age at diagnosis was 70 years (range 49–80) and median follow-up, 5.8 years. Late grade 1, 2 and 3 GI toxicity were 13%, 24%, and 2.6%, respectively. Late grade 1, 2, 3 GU toxicity were 29%, 21%, and 8%, respectively. Sexual toxicity was evaluated in 19 patients to be grade 1, 2 in 11% and grade 3 in 16%. Multivariate analysis showed that patients with higher values of rectum V50 associated with late GI toxicity (P=0.025). Patients with PSA ≤8 (P=0.048) or comorbidities (P=0.013) at diagnosis were associated with higher late GU toxicity. Additionally, PSA ≤8 also associated with moderate (grade ≥2) late GU toxicity in the multivariate analysis (P=0.028).ConclusionsHypofractionated HT can be delivered safely with limited rates of moderate and severe late toxicity. The proportion of the rectum that receives a moderate and high dose, having comorbidities, and PSA at diagnosis seem to associate with long term toxicity

Myeloablative therapy against high risk Ewing's sarcoma: A single institution experience and literature review

BackgroundAttempts to improve survival outcomes of patients with high risk Ewing's sarcoma (ES) have focused on chemotherapy dose intensification strategies.AimThe objective of this study is to retrospectively evaluate clinical characteristics and outcome of pediatric patients with high risk ES treated at a single institution.Materials and methodsFrom 1995 to 2008, seventeen patients (male:female, 14:3) were treated with dose-intensive therapy in our institution. Median age at diagnosis was 10 years (range: 2–15). Seven patients had metastases at diagnosis (lung in 6 cases and bone in one case). Eleven patients presented with unresectable disease. Fifteen (88.2%) received the Spanish Society of Pediatric Oncology protocol which includes six cycles of vincristine, doxorubicin, ifosfamide and etoposide. Two out of the six cases that were resectable received postoperative radiation. In addition, eleven patients received definitive radiation therapy. Finally, twelve (70.5%) out of 17 patients received myeloablative therapy with melphalan/etoposide. The rest of patients (N[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]5) received busulfan/melphalan.ResultsMedian follow-up was 78 months (range: 15–155 months). Initial responses were complete in all patients, but 9 of them developed progression disease. Seven patients became long-term event-free survivors. No patient died of toxicity after transplantation. The 2- and 5-year overall survival rates for all patients were 93% and 73%, respectively. Event-free survival rates were 74% and 54% at 2 and 5 years, respectively.ConclusionThis single-institution experience suggests that myeloablative therapy against high risk ES is effective and safe

miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

Background: Sorafenib constitutes a suitable treatment alternative for patients with advanced hepatocellular carcinoma (HCC) in whom atezolizumab + bevacizumab therapy is contraindicated. The aim of the study was the identification of a miRNA signature in liquid biopsy related to sorafenib response. Methods: miRNAs were profiled in hepatoblastoma HepG2 cells and tested in animal models, extracellular vesicles (EVs), and plasma from HCC patients. Results: Sorafenib altered the expression of 11 miRNAs in HepG2 cells. miR-200c-3p and miR-27a-3p exerted an anti-tumoral activity by decreasing cell migration and invasion, whereas miR-122-5p, miR-148b-3p, miR-194-5p, miR-222-5p, and miR-512-3p exerted pro-tumoral properties by increasing cell proliferation, migration, or invasion, or decreasing apoptosis. Sorafenib induced a change in EVs population with an increased number of larger EVs, and promoted an accumulation of miR-27a-3p, miR-122-5p, miR-148b-3p, miR-193b-3p, miR-194-5p, miR-200c-3p, and miR-375 into exosomes. In HCC patients, circulating miR-200c-3p baseline levels were associated with increased survival, whereas high levels of miR-222-5p and miR-512-3p after 1 month of sorafenib treatment were related to poor prognosis. The RNA sequencing revealed that miR-200c-3p was related to the regulation of cell growth and death, whereas miR-222-5p and miR-512-3p were related to metabolic control. Conclusions: The study showed that Sorafenib regulates a specific miRNA signature in which miR-200c-3p, miR-222-5p, and miR-512-3p bear prognostic value and contribute to treatment response

Immunological and inflammatory changes after simplifying to dual therapy in virologically suppressed HIV-infected patients through week 96 in a randomized trial

Objectives: To evaluate whether simplification of antiretroviral treatment to dual therapy (DT) negatively impacts immune recovery (IR), immune activation and inflammation (IA/I), and HIV reservoir. Methods: An open-label, single-centre, randomized controlled trial conducted in adult virologically suppressed HIV-infected patients on triple therapy (TT) with elvitegravir-cobicistat, emtricitabine and tenofovir alafenamide or dolutegravir (DTG), abacavir, and lamivudine (3TC). Participants were ran domized to continue TT or switch to DTG, or darunavir/cobicistat (DRVc) plus 3TC. IR was assessed by CD4þ/CD8þ ratio at 48 and 96 weeks. Changes in immune activation, proliferation, exhaustion, senes cence, and apoptosis in CD4þ and CD8þ T cells, plasma sCD14, hsCRP, D-dimers, b2-microglobulin, IL-6, TNF-a and IP-10 levels, cell-associated HIV-DNA (CA-DNA), and unspliced HIV-RNA (usRNA) were also analysed. Results: One hundred and fifty-one participants were enrolled. Fourteen patients did not complete the follow up. In the ITT and PP analysis, the IR was similar between the treatment arms. In the ITT analysis, the median increase in CD4þ/CD8þ ratio was 0.10, 0.04, and 0.07 at week 48, and 0.09, 0.05, and 0.08 at week 96 for TT, DTG/3TC, and DRVc/3TC, respectively. After adjusting for confounding factors, the slopes of changes in CD4þ/CD8þ ratio over time were independent of treatment (F ¼ 1.699; p ¼ 0.436) and related only to baseline values (F ¼ 756.871; p ¼ 0.000). There were no differences in IA/I, CA-DNA, or usRNA between treatment arms. Discussion: Both IR and IA/I, CA-DNA, and usRNA were similar in the three treatment groups, regardless of maintaining TT or simplifying to DTG/3TC or DRVc/3TC in virologically suppressed HIV-infected pa tients

Cumulative incidence of occult cancer over 24 months attending score (≤2 vs. ≥3 points).

<p>Time-to-event data.</p

Clinical characteristics of patients with vs. without occult cancer.

<p>Clinical characteristics of patients with vs. without occult cancer.</p

Flowchart patients.

<p>Flowchart patients.</p

Multivariable analysis replacing chronic lung disease for current smoke.

<p>Multivariable analysis replacing chronic lung disease for current smoke.</p