Extracellular vesicles-encapsulated microRNA-10a-5p shed from cancer-associated fibroblast facilitates cervical squamous cell carcinoma cell angiogenesis and tumorigenicity via Hedgehog signaling pathway

Cancer shared this article with you from Inoreader Extracellular vesicles-encapsulated microRNA-10a-5p shed from cancer-associated fibroblast facilitates cervical squamous cell carcinoma cell angiogenesis and tumorigenicity via Hedgehog signaling pathway Via Cancer Gene Therapy - Issue - nature.com science feeds View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Multi-institutional Comparative Analysis of Proton and Photon Therapy-Induced Hematologic Toxicity in Patients With Medulloblastoma

Cancer shared this article with you from Inoreader A Multi-institutional Comparative Analysis of Proton and Photon Therapy-Induced Hematologic Toxicity in Patients With Medulloblastoma Via ScienceDirect Publication: International Journal of Radiation Oncology*Biology*Physics Publication date: Available online 23 November 2020 Source: International Journal of Radiation Oncology*Biology*Physics Author(s): Kevin X. Liu, Myrsini Ioakeim-Ioannidou, Matthew S. Susko, Avani D. Rao, Beow Y. Yeap, Antoine M. Snijders, Matthew M. Ladra, Jennifer Vogel, Cierra Zaslowe-Dude, Karen J. Marcus, Torunn I. Yock, Clemens Grassberger, Steve E. Braunstein, Daphne A. Haas-Kogan, Stephanie A. Terezakis, Shannon M. MacDonald View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Feasibility and safety of exercise training and nutritional support prior to haematopoietic stem cell transplantation in patients with haematologic malignancies

Cancer shared this article with you from Inoreader Feasibility and safety of exercise training and nutritional support prior to haematopoietic stem cell transplantation in patients with haematologic malignancies Via Latest Results for BMC Cancer Abstract Background Prehabilitation with regular exercise and nutritional care for patients undergoing surgeries for malignant disease was recently introduced to increase physiologic reserve prior to the procedure, accelerate recovery and improve outcomes. This study aimed to investigate the feasibility and safety of combined exercise training and nutritional support in patients with haematologic malignancies prior to haematopoietic stem cell transplantation (HSCT). Methods In this single-arm pilot study, 34 HSCT candidates were enrolled at least two weeks before admission for the procedure. Patients performed aerobic exercises at least 4 days per week for 20–30 min and strength exercises 3 days per week for 10–20 min. They received daily supplements of whey protein (0.3–0.4 g/kg body weight) and oral nutritional supplements if needed. The primary endpoints were feasibility (acceptability > 75%, attrition < 20%, adherence > 66%) and safety. The secondary endpoints were fat-free mass (FFM), muscle strength, physical performance and health-related quality of life (HRQoL) at HSCT. Results The rate of acceptability, attrition and adherence to aerobic exercise, strength exercise and protein supplement consumption was 82.4, 17.8, 71, 78 and 80%, respectively. No severe adverse events were reported. Twenty-eight patients participated in the study for a median of 6.0 weeks (range, 2–14). They performed aerobic exercises 4.5 days per week for 132 min per week and strength exercises 3.0 times per week. Patients consumed 20.7 g of extra protein daily. At the end of the programme, we recorded increases of 1.1 kg in FFM (p = 0.011), 50 m in walking distance in the 6-min walking test (6MWT) (p < 0.001), 3.3 repetitions in the 30-s chair-stand test (30sCST) score (p < 0.001) and 2.6 kg in handgrip strength (p = 0.006). The EORTC QLQ-C30 scores improved by 8.6 (p < 0.006) for global health status, 8.3 (p = 0.009) for emotional functioning, and 12.1 (p =  0.014) for social functioning. There was less fatigue, nausea and insomnia (p < 0.05). Conclusions Our study shows that a multimodal intervention programme with partially supervised exercise training combined with nutritional support prior to HSCT is feasible and safe. Patients showed improvements in FFM, physical performance and HRQoL. Additional research is needed to assess the possible positive effects of such interventions. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Eradication of T-ALL cells by CD7 targeted universal CAR-T cells and initial test of ruxolitinib-based CRS management

Cancer shared this article with you from Inoreader Eradication of T-ALL cells by CD7 targeted universal CAR-T cells and initial test of ruxolitinib-based CRS management Via Clinical Cancer Research Online First Articles Purpose：Although chimeric antigen receptor T cell (CAR-T) therapy development for B cell malignancies has made significant progress in the last decade, broadening the success to treating T-ALL has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an "off-the-shelf" allogeneic CAR-T product targeting T cell antigen CD7. Here we report two patients as case reports with relapsed/refractory T-ALL who were treated with GC027. Experimental Design：Both of the two trials reported are open-labeled and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy. Result：Robust expansion of CAR-T cells along with rapid eradication of CD7+ T-lymphoblasts were observed in the peripheral blood, bone marrow and cerebrospinal fluid. Both patients achieved complete remission (CR) with no minimal residual disease (MRD) detectable. At data cut off Sep.30, 2020 one of the two patients remains in ongoing remission for over one year after CAR-T cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Ruxolitinib showed promising activity in a preclinical study conducted at our center. No Graft-versus-host-disease (GvHD) was observed. Conclusion：The two case reports demonstrate that a stand alone therapy with this novel CD7 targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select r/r T-ALL patients. GC027- might have a potential to be a promising new approach for treating refractory/relapsed T - ALL. Further studies are warranted. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Starting dose selection and dose escalation for oncology small molecule first-in-patient trials: learnings from a survey of FDA-approved drugs

Cancer shared this article with you from Inoreader Starting dose selection and dose escalation for oncology small molecule first-in-patient trials: learnings from a survey of FDA-approved drugs Via Latest Results for Cancer Chemotherapy and Pharmacology Abstract The ideal starting dose for an oncology first-in-patient (FIP) trial should be low enough to be safe but not too far removed from therapeutically relevant doses. A low starting dose combined with small dose increments could lead to a lengthy dose escalation and could expose patients unnecessarily to sub-therapeutic dosing. In the current analyses, we reviewed 59 approved small molecule oncology drugs (SMOD) with the overarching goals to assess the current approaches of FIP starting dose selection and dose escalation, and to identify potential opportunities for improving trial efficiency and minimizing number of patients receiving sub-therapeutic dose levels. Of 59 SMODs, the majority (~ 66%) were kinase inhibitors and ~ 73% were approved for solid tumor indications. Most of the trials used a 3 + 3 design for dose escalation and had a median (range) of 4 cohorts (0–11) to reach MTD from the starting dose. The maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) to starting dose ratio was highly variable with a median (range) of 8 (0.25–125). About 71% of the FIP trials had < 6 dose escalation steps to reach MTD or RP2D (with 15% ≤ 2 dose escalations), but the remaining 29% of trials had ≥ 6 dose escalation steps to reach MTD or RP2D suggesting that there is still room for increasing efficiency by reducing the number of dose escalation steps, reducing the variability in MTD to starting dose ratio, and consequently reducing significant number of patients exposed at sub-therapeutic doses in the dose escalation phase of FIP study. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study

Cancer shared this article with you from Inoreader Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study Via Latest Results for BMC Cancer Abstract Background Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients. Methods IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University. Results This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally. Conclusion These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer

Cancer shared this article with you from Inoreader The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer Via Latest Results for BMC Cancer Abstract Background The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. Methods Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. Results Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642–0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3–4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1–2N1 disease (P = 0.191). Conclusions Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3–4N1 and T1-4N2–3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1–2N1 TNBC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Analysis of the expression and potential molecular mechanism of interleukin-1 receptor antagonist (IL1RN) in papillary thyroid cancer via bioinformatics methods

Cancer shared this article with you from Inoreader Analysis of the expression and potential molecular mechanism of interleukin-1 receptor antagonist (IL1RN) in papillary thyroid cancer via bioinformatics methods Via Latest Results for BMC Cancer Abstract Background Interleukin-1 receptor antagonist (IL1RN) has been reported as a biomarker of many cancers. However, the biological function of IL1RN in papillary thyroid carcinoma (PTC) remains undetermined. Methods We obtained IL1RN expression data from The Cancer Genome Atlas (TCGA) database. Enrichment analysis of coexpressed genes and IL1RN methylation analysis were performed via LinkedOmics. The correlations between IL1RN and immune infiltrates were investigated via ESTIMATE, TIMER and TISIDB. We analyzed the association of IL1RN expression with pancancer overall survival (OS) via Gene Expression Profiling Interactive Analysis (GEPIA). Results IL1RN showed higher expression levels and lower methylation levels in PTC tissues than in normal tissues. Higher IL1RN expression was significantly associated with shorter progression-free survival (PFS), advanced tumor stage, tumor metastasis, increased incidence of BRAF mutations, and decreased incidence of N-RAS and H-RAS mutations. Genes coexpressed with IL1RN participate primarily in immune-related pathways. IL1RN expression positively correlated with immune infiltration, tumor progression and poor OS for all cancers. Conclusions IL1RN is a good prognostic and diagnostic biomarker for PTC. IL1RN may promote thyroid cancer progression through immune-related pathways. Methylation may act as an upstream regulator of IL1RN expression and biological function. Additionally, IL1RN was shown to have broad prognostic value in a pancancer cohort. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Benefit of dosimetry distribution for patients with multiple brain metastases from non-small cell lung cancer by a Cyberknife stereotactic radiosurgery (SRS) system

Cancer shared this article with you from Inoreader Benefit of dosimetry distribution for patients with multiple brain metastases from non-small cell lung cancer by a Cyberknife stereotactic radiosurgery (SRS) system Via Latest Results for BMC Cancer Abstract Background In order to obtain a high dose conformal index of tumor and steep dose fall-off in healthy tissues for brain metastasis stereotactic radiosurgery (SRS), the aim of this study was to investigate SRS planning optimization by comparing one multiple-lesions plan (MLP) with multiple single-lesion plans (SLPs) for patients with multiple brain metastases using the Cyberknife (CK) system. Methods Fifty non-small cell lung cancer (NSCLC) patients (28 males and 22 females) with 2–4 brain metastases, inter-tumour distances less than 3 cm, were retrospectively replanned with the original prescription dose (12–32 Gy) in the original fractions (1–3). Two different clinical CK SRS plans (SLPs and MLP) were generated for the same patients with the same collimator and prescription isodose line (62–68%) by the CK Multiplan System. Both SLPs and MLP were able to achieve > 95% PTV volume covered prescription dose and met the Timmerman 2011 organs at risk (brainstem, optic nerve and pituitary) constraints. Results Compared with those in the SLPs, the maximum dose (Dmax) and mean dose (Dmean) of brainstem in the MLP were reduced 0.22–3.13% (2.62%) and 2.71–12.56% (5.57%), respectively, all P < 0.05. Meanwhile, the volumes of the whole brain minus the tumors that received a single dose equivalent of 8–16 Gy (V8Gy-V16Gy) were effectively reduced in the MLP. The treatment time parameters, the total number of beams and monitor units, of the MLP were reduced by 3.31 and 1.47% (P < 0.05), respectively. Although there were a few differences in the conformity index (CI) and homogeneity index (HI) between the two treatment plans, the differences were not statistically significant (P = 2.94 and 1.08 > 0.05). Conclusion One multiple-lesions plan for brain metastases could achieve higher precision in the target and lower doses in healthy tissue while shortening the treatment time and improving the treatment efficiency over multiple single-lesion plans. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy

Cancer shared this article with you from Inoreader Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy Via Latest Results for Radiation Oncology Abstract Purpose To investigate predictors of cognitive decline after whole brain radiotherapy (WBRT) for brain metastases. Methods A secondary analysis of a phase 2 clinical trial was conducted in patients who received stereotactic radiosurgery for 1–10 brain metastases and WBRT (NCT01046123). The Montreal Cognitive Assessment (MoCA) was performed at baseline and every 3 months after WBRT. Baseline T2-weighted fluid attenuation inversion recovery magnetic resonance imaging was independently assessed by two neuroradiologists for the presence of white matter hyperintensities (WMH) using the Fazekas visual rating scale. WMH were also manually segmented for volumetric analysis. Univariable and multivariable logistic regression were used to test the association between baseline variables and MoCA score decline. Results Forty-six patients survived ≥ 3 months after treatment. Age (OR 1.12 (1.04–1.21), p < 0.01), baseline WMH volume (OR 1.20, 95% CI 1.06–1.52, p = 0.02) and baseline Fazekas score ≥ 3/6 (OR 6.4, 95% CI 1.7–24.7, p < 0.01) were predictive of MoCA score decline. In multivariable analysis, age was the only significant predictor of MoCA decline. However, all three patients with pre-treatment leukoencephalopathy (Fazekas score = 6/6) had notable adverse outcomes due to cognitive impairment: one required full-time home nursing support and two were institutionalized. Conclusion A greater decline in cognition after WBRT was observed in older patients and patients with a higher baseline WMH burden. Although this study is small and hypothesis-generating, we propose that radiation oncologists should exercise caution in prescribing WBRT if leukoencephalopathy is present on pre-treatment imaging. Trial Registration: clinicaltrials.gov identifier NCT01046123. First posted January 11, 2010. https://clinicaltrials.gov/ct2/show/NCT01046123 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Short-term mortality risks among patients with non-metastatic bladder cancer

Cancer shared this article with you from Inoreader Short-term mortality risks among patients with non-metastatic bladder cancer Via Latest Results for BMC Cancer Abstract Background Population-based analysis for the short-term non-bladder cancer related mortality among patients with non-metastatic bladder cancer is currently lacking. The objective of the current study was to assess and quantify cause of death after bladder cancer diagnosis. Methods The custom Surveillance, Epidemiology, and End Results (SEER) dataset for standardized mortality ratios (SMRs) was utilized to identify 24,074 patients who were diagnosed with nonmetastatic (M0) bladder cancer from 2014 to 2015. SMRs for causes of death were calculated. Risk factors for bladder cancer-specific mortality, competing mortality, second-cancer mortality, and noncancer mortality were determined using either multivariable Cox or competing risk regression models. Results Among all the 4179 (17.4%) deaths occurred during the follow-up period, almost half of them (44.2%) were attributed to non-bladder cancer cause, including second non-bladder cancer (10%) and other non-cancer causes (34.2%). The most common noncancer causes of death were heart diseases followed by chronic obstructive pulmonary disease. Patients had a higher risk of death from second malignancies (SMR, 1.59; 95% CI, 1.47–1.74) compared with death from first malignancies in the US general population, and also had higher risks of death from heart diseases (SMR, 1.29; 95% CI, 1.18–1.40) and chronic obstructive pulmonary disease (SMR, 1.52; 95% CI, 1.29–1.79) compared with the US general population. Additionally, some risk factors for competing second malignancies or noncancer mortality were determined, such as age, gender, marital status and treatment modalities. Conclusions Death from non-bladder cancer cause contributed to almost half of all deaths in bladder cancer survivors during the short-term follow-up period. These findings can inform medical management and assist clinicians in counseling those survivors regarding their short-term health risks. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.