A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China

Bone metastases are common in patients with advanced cancer. Bisphosphonates (BPs) could prevent or delay the development of skeleton-related events (SREs). The present study aimed to identify the clinical fea...

from Cancer via ola Kala on Inoreader http://ift.tt/1TtbMy0
via IFTTT

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative, metastatic breast cancer

Both hormonal therapy (HT) and maintenance capecitabine monotherapy (MCT) have been shown to extend time to progression (TTP) in patients with metastatic breast cancer (MBC) after failure of taxanes and anthra...

from Cancer via ola Kala on Inoreader http://ift.tt/1SnTq2g
via IFTTT

Dose escalation study of proton beam therapy with concurrent chemotherapy for stage III non-small cell lung cancer

Summary

The purpose of this study is to determine the recommended dose (RD) of proton beam therapy (PBT) for inoperable stage III non-small cell lung cancer (NSCLC). We tested two prescribed doses of PBT;66 Gy (relative biological effectiveness; RBE) in 33 fractions and 74 Gy (RBE) in 37 fractions in arms 1 and 2, respectively. The planning target volume (PTV) included the primary tumor and metastatic lymph nodes with adequate margins. Concurrent chemotherapy included intravenous cisplatin (60 mg/m², day 1) and oral S-1 (80, 100 or 120 mg based on body surface area, days 1-14), repeated as 4 cycles every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 3 or severe toxicities related to PBT during days 1-90. Each dose level was performed in 3 patients, and then escalated to the next level if no DLT occurred. When 1 patient developed a DLT, 3 additional patients were enrolled. Overall, nine patients (5 men, 4 women; median age, 72 years) were enrolled, including 6 in arm 1 and 3 in arm 2. The median follow-up time was 43 months, and the median progression-free survival was 15 months. In arm 1, grade 3 infection occurred in 1 of 6 patients, but no other DLT was reported. Similarly, no DLT occurred in arm 2. However, 1 patient in arm 2 developed grade 3 esophageal fistula at 9 months after the initiation of PBT. Therefore, we determined that 66 Gy (RBE) is the RD from overall clinical viewpoints. Clinical trial registration no.:UMIN000005585.

This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/1Wm1DFR
via IFTTT

Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells

Abstract

Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies. The generation of conventional treatments has improved, but approximately 50 % of patients with CRC who undergo potentially curative surgery ultimately relapse and die, usually as a consequence of metastatic disease. Our previous findings showed that engagement of the cellular prion protein (PrP^C) to its ligand HSP70/90 heat shock organizing protein (HOP) induces proliferation of glioblastomas. In addition, PrP^C has been described as an important modulator of colorectal tumor growth. Here, we investigated the biological relevance of the PrP^C-HOP interaction in CRC cells. We demonstrate that HOP induced the migration and invasion of CRC cell lines in a PrP^C-dependent manner and that phosphorylation of the ERK1/2 pathway is a downstream mediator of these effects. Additionally, we show that a HOP peptide with the ability to bind PrP^C and abolish the PrP^C-HOP interaction inhibited the migration and invasion of CRC cells. Together, these data indicate that the disruption of the PrP^C-HOP complex could be a potential therapeutic target for modulating the migratory and invasive cellular properties that lead to metastatic CRC.

from Cancer via ola Kala on Inoreader http://ift.tt/21cEXZm
via IFTTT

Clinical Case Report: Yoga for Fatigue in Five Young Adult Survivors of Childhood Cancer

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


from Cancer via ola Kala on Inoreader http://ift.tt/21cEgPG
via IFTTT

Deliveries After Malignant Disease Before Pregnancy: Maternal Characteristics, Pregnancy, and Delivery Complications

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


from Cancer via ola Kala on Inoreader http://ift.tt/1rcT9VP
via IFTTT

Double primary malignant fibrous histiocytoma and squamous cell carcinoma of the larynx treated with laser laryngeal conservation surgery

PD Karkos, S Dova, S Sotiriou, K Markou and I Kostopoulos

from Cancer via ola Kala on Inoreader http://ift.tt/24f6VFB
via IFTTT

Unmet Needs for Psychosocial Care in Hematologic Malignancies and Hematopoietic Cell Transplant

Abstract

Individuals diagnosed with hematologic malignancies experience significant unmet psychological, physical, informational, financial, and spiritual needs. The goal of the current review is to summarize and highlight recent research focused on these issues in the diagnosis and treatment periods and beyond. The review also describes the needs of adolescent and young adult (AYA) and pediatric patients. While a large body of research has reported on unmet needs among adult hematologic cancer patients, there is far less data regarding the challenges confronted by AYA and pediatric populations. Available data suggests that among all age groups, hematopoietic cell transplantation (HCT) is a risk factor for greater unmet needs. Recommendations for screening and evidence-based interventions to prevent or ameliorate unmet needs are provided. Future research is needed to develop additional evidence-based psychosocial interventions with a focus on hematologic cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/21bTK6B
via IFTTT

Neoadjuvant treatment for rectal cancer—A value-based proposition

Over the last decade, the use of neoadjuvant chemo-radiation has been an integral part of the care of patients with locally advanced rectal cancer. However, emerging data are beginning to challenge the current treatment paradigm of neoadjuvant chemo-radiation followed by radical resection and subsequent adjuvant chemotherapy. Going forward, the challenge will be to identify patients for whom radiation can be safely omitted and those for whom it can potentially provide added oncologic value. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/24ePZiH
via IFTTT

Efficacy and safety of stereotactic body radiation therapy for the treatment of pulmonary metastases from sarcoma: A potential alternative to resection

Background/Objectives

Oligometastatic sarcoma pulmonary metastases (PM) are typically treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) can be an alternative to surgery that can achieve high rates of local control (LC) with limited toxicity.

Methods

Thirty consecutive sarcoma patients received SBRT to 39 PM's from 2011 to 2015 at two university hospitals to a median dose of 50 Gy in 4–5 fractions with CyberKnife or linear accelerator. Patients underwent CT or PET/CT scans q3 months after SBRT.

Results

77% received prior chemotherapy, 70% had 1–3 prior pulmonary resections, and 26% received prior thoracic radiotherapy. Median lesion size was 2.4 cm (range 0.5–8.1 cm). Median follow-up was 16 and 23 months for patients alive at last follow-up. At 12 and 24 months, LC was 94% and 86%, and OS was 76% and 43%. LC and OS did not differ by SBRT technique, fractionation regimen, lesion location, histology, or size (all P > 0.05). Three developed grade 2 chest-wall toxicity with no other grade ≥2 toxicities.

Conclusions

This is the largest series on SBRT for sarcoma PM's and demonstrates that SBRT is well-tolerated with excellent LC across tumor locations and sizes. SBRT should be considered in these patients, and prospective studies are warranted. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/1VTGcN6
via IFTTT

Outcomes of one-side versus two-sides recipient vessels for bilateral breast reconstructions with bilateral DIEP flaps

Background

This study was to compare the use of one-side versus two-sides recipient vessels in either bilateral breast reconstructions or unilateral breast reconstruction with contralateral augmentation using bilateral DIEP flaps.

Patients and Methods

A retrospective review including all cases of bilateral breast reconstructions and unilateral reconstruction with contralateral augmentation with DIEP flaps was performed. Patient's demographics, surgical variables, and outcome were collected. Two distinct cohorts based on the recipient vessel techniques, one-side versus two-sides, were compared.

Results

A total of 25 patients with 50 split-DIEP flaps were included, with one-side recipient vessels used in 19 patients and two-sides recipient vessels in 6 patients. Ischemia time was significantly reduced in one-side recipient group compared to two-sides recipient vessels group (62.4 ± 21.3 vs. 105.9 ± 32.5, P < 0.001). There was no statistic difference in venous congestion, partial flap loss, or fat necrosis in both groups.

Conclusions

Using one-side recipient vessels for bilateral breast reconstructions with unilateral breast reconstruction with contralateral augmentation using differentially split DIEP flaps presents a high success rate, acceptable ischemia time, and minimal complications for small to medium volume breast reconstructions. Utilizing this method can reduce the ischemia time and spare one side internal mammary vessels. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/24ePWn2
via IFTTT

Control of primary lesions using resection or radiotherapy can improve the prognosis of metastatic colorectal cancer patients

Background

Control of the primary lesions in metastatic colorectal cancer (mCRC) is still controversial. For rectal cancer patients, not only resection but also irradiation is expected to provide palliative effects. We investigated the effects of resection and irradiation of primary lesions (local control) on the prognosis of mCRC patients.

Patients

Forty-seven patients with mCRC at our institute were examined, with 34 in the local controlled group and 13 in the uncontrolled group.

Results

The median survival time (MST) of the local controlled and uncontrolled groups were 2.90 and 1.39 years (P = 0.028). Cox proportional hazard regression analysis showed that local control was an independent prognostic factor (P < 0.05). The patients who underwent primary lesion resection had significantly longer MST (2.90 vs. 1.39 years, P = 0.032) than those in the uncontrolled group. In rectal cancer patients, the patients who underwent irradiation to control the primary lesions had a significantly longer MST than the uncontrolled patient group (1.97 vs. 1.39 years, P = 0.019).

Conclusions

Local control of primary lesions may improve the prognosis in mCRC patients. In rectal cancer patients with metastasis, not only resection but also irradiation of the primary lesions may be a useful therapeutic strategy. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/1VTGcg7
via IFTTT

Programmed death ligand-1 expression is associated with poor disease free survival in salivary gland carcinomas

Background and Objectives

The immune checkpoint ligand programmed death ligand-1 (PD-L1) is expressed in various carcinomas and allows carcinoma cells to elude the immune system. PD-L1 expression is associated with the response to anti-programmed death 1 (PD-1)/PD-L1 drugs. This study aimed to clarify the relationship between PD-L1 expression and clinicopathological factors of salivary gland carcinomas (SGCs) and identify its clinical significance.

Methods

PD-L1 expression was examined by immunohistochemical analysis using a tissue microarray comprised of 219 surgically resected SGC specimens. Detailed clinicopathological factors, including patient outcome, were available for all cases.

Results

A case showing complete membranous expression of PD-L1 in more than 1% of whole carcinoma cells was considered positive by ROC analysis. A total of 50 (22.8%) patients showed PD-L1 expression in SGC cells. Positive PD-L1 expression was significantly associated with poor disease free survival (P < 0.001) and overall survival (P < 0.001). Multivariate analysis revealed that positive PD-L1 expression was one of the independent predictors for poor disease free survival (hazard ratio = 2.287, 95% confidence interval = 1.24–4.15; P = 0.008).

Conclusions

Positive PD-L1 expression was significantly associated with poor disease free survival of SGCs, suggesting that antibody therapies targeting PD-1/PD-L1 may have potential application in SGCs. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/24ePYeu
via IFTTT

Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma

Background and Objectives

Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang-receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2-expressing monocytes (TEMs) in cholangiocarcinoma.

Methods

We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution of Angs (Ang 1/Ang 2) and TEMs, as defined by co-expression of CD14 and Ang receptor TIE2. Ang expression and abundance of TEMs were correlated with clinicopathologic characteristics, tumor recurrence and patients' survival.

Results

High Ang 1 expression correlated with reduced metastasis (P < 0.05). Patients characterized by invading Ang-receptor bearing TEMs in tumor showed lower tumor recurrence (P < 0.05). Furthermore, TEMs in tumor and tumor invasive front correlated with increased survival (P < 0.05). TEMs in tumor invasive front were confirmed as independent prognosticator in multivariate survival analysis (P < 0.05).

Conclusions

High Ang 1 expression in hilar cholangiocarcinoma and infiltration of TEMs defines a subgroup of patients with beneficial tumor characteristics and prolonged survival. Besides suggested functional links between Ang expression and recruitment of TEMs, our data have possible clinical implications as novel diagnostic tools. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/1VTGbJ6
via IFTTT

What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures

Objective

To review our 25-year experience with hyperthermic intra-peritoneal chemotherapy (HIPEC).

Background

Combining cytoreductive surgery (CRS) and HIPEC as local treatments for peritoneal carcinomatosis (PC) was proposed 25 years ago.

Methods

A prospective database of all patients undergoing HIPEC for PC since 1989 was searched for clinicopathological data, 90-day morbidity and mortality, and survival.

Results

Among 1,125 HIPEC procedures, PC origin was colorectal (342; 30%), ovarian (271; 24%), pseudomyxoma peritonei (189; 17%), gastric (127; 11%), malignant mesothelioma (84; 8%), or other (112; 10%). Between 2004–2009 (n = 321) and 2010–2015 (n = 560), the median peritoneal cancer index decreased (11 vs. 8; P < 0.001), fewer patients underwent incomplete cytoreduction (CC2-3: 4% vs. 0.5%; P < 0.001), and more were included in randomized trials (5% vs. 16%; P < 0.001). Postoperative morbidity (52% vs. 50%, P = 0.672) was not different, but mortality significantly decreased (5% vs. 2%; P = 0.030). Median overall-survival was 42 months, and improved significantly for each 5-year period except for 2006–2010 vs. 2011–2015 (P = 0.097). The 10-year survival without recurrence was 53%, 14%, 4%, 10%, and 9% for pseudomyxoma, mesothelioma, ovarian, colorectal, and gastric PC, respectively.

Conclusion

This study demonstrated that CRS and HIPEC provide long-term survival irrespective of PC origin, and survival improves with experience. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/24ePSDR
via IFTTT

Acupuncture for Dyspnea in Lung Cancer: Results of a Feasibility Trial

Purpose. Dyspnea is a common and distressing symptom for patients with lung cancer (LC) because of disease burden, therapy toxicity, and comorbid illnesses. Acupuncture is a centuries-old therapy with biological plausibility for relief of dyspnea in this setting. This pilot study aimed to evaluate the feasibility and preliminary effectiveness of acupuncture for dyspnea among patients with LC. Methods. Eligible patients had a diagnosis of LC and clinically significant dyspnea without a clear organic cause. The treatment consisted of 10 weekly acupuncture sessions, with a follow-up visit 4 weeks after therapy. The primary outcome was dyspnea severity as measured using a validated Numerical Rating Scale (NRS) of 0 to 10 (10 being "most severe shortness of breath imaginable"). Results. We enrolled 12 patients in the study. The median age was 64.5 years; 66.7% of the patients were female, and 66.7% were Caucasians. Among those enrolled, 10 (83.3%) were able to complete all 10 acupuncture sessions. Acupuncture was well tolerated; adverse events were mild and self-limited. Mean (SD) dyspnea scores on the NRS improved from 6.3 (1.7) at baseline to 3.6 (1.9; P = .003) at the end of treatment and 3.2 (2.3; P = .008) at follow-up. Fatigue and quality of life also improved significantly with acupuncture (P < .05). Conclusion. Among patients with LC, acupuncture was well tolerated and exhibited promising preliminary beneficial effects in the treatment of dyspnea, fatigue, and quality of life. Performing a trial in this population appears feasible.

from Cancer via ola Kala on Inoreader http://ift.tt/24eHxzU
via IFTTT

Retrospective analysis of bevacizumab-induced hypertension and clinical outcome in patients with colorectal cancer and lung cancer

Abstract

Bevacizumab(Avastin^®), a humanized therapeutic monoclonal antibody that targets vascular endothelial growth factor, is widely used in cancer treatment. Patients who are treated with bevacizumab have an increased risk of developing systemic hypertension. However, the relationship between bevacizumab-induced hypertension and clinical outcome remains unclear. We aimed to evaluate the effect of bevacizumab-induced hypertension in terms of prognosis in patients with colorectal cancer and non-small cell lung cancer. The study included 632 patients, 317 patients with non-small cell lung cancer and 315 patients with colorectal cancer. All patients were treated with bevacizumab in combination with standard chemotherapy protocols, between April 2007 and December 2014. Blood pressure was measured before each treatment cycle. In the patient group with colorectal cancer, treated with bevacizumab, Grade 2–3 hypertension was present in 27.6%. In hypertensive patients with colorectal cancer, median overall survival was 42.6 months, compared with 20.6 months for normotensive patients in this group (P = 0.00071). In the patient group with non-small cell lung cancer, treated with bevacizumab, Grade 2–3 hypertension was present in 20.5%. In hypertensive patients with non-small cell lung cancer, median overall survival was 43.0 months, compared with 26.3 months for normotensive patients in this group (P = 0.00451). Patients who developed hypertension during treatment with bevacizumab for colorectal cancer and non-small cell lung cancer had significantly prolonged overall survival when compared with normotensive patients. Bevacizumab-induced hypertension may represent a biomarker for clinical benefit in cancer patients treated with bevacizumab.

The most common bevacizumab-related adverse event was hypertension. Patients who developed hypertension during treatment with bevacizumab for colorectal cancer and non-small lung cancer had significantly prolonged overall survival.

from Cancer via ola Kala on Inoreader http://ift.tt/1Wlfzj6
via IFTTT

Flow cytometry-based characterization of underlying clonal B and plasma cells in patients with light chain amyloidosis

Abstract

Systemic amyloid light chain (AL) amyloidosis is a life-threatening protein deposition disorder; however, effective therapy can dramatically improve the prognosis of AL patients. Therefore, accurate diagnosis of the underlying hematologic disease is important. Multi-parameter flow cytometry (MFC) is a reliable method to analyze lymphatic neoplasias and to detect even a small lymphatic clone. We analyzed the presence of clonal plasma cell (PC) and B cells in the bone marrow of 63 patients with newly diagnosed AL amyloidosis by MFC. We compared the results with the levels of monoclonal protein, the histopathology and cytogenetic results. As reference of light chain restriction, we used the immunohistochemical results of κ or λ positive amyloid deposits in various tissues. MFC identified underlying clonal lymphatic cells in all but two patients (61 of 63, 97%). Sixty-one patients harbored malignant PCs, whereas B-cell lymphomas were identified in two patients. Furthermore, MFC indicated at least one putative immunotherapeutical target (CD20, CD38, CD52, or SLAMF7) on malignant PCs in all but one patient. These results demonstrate that MFC is a reliable tool for an accurate diagnosis of the underlying hematologic disease and the detection of potential immunotherapeutical targets in patients with AL amyloidosis.

Systemic amyloid light chain (AL) amyloidosis is a life-threatening protein deposition disorder and an accurate diagnosis of the underlying hematologic disease is important to provide effective therapy. We analyzed the presence of clonal plasma cell (PC) and B cells in the bone marrow of 63 patients with newly diagnosed AL-amyloidosis by multi-parameter flow cytometry (MFC). MFC identified underlying clonal lymphatic cells in all but two patients (61 of 63, 97%). Sixty-one patients harbored malignant PCs, whereas B-cell lymphomas were identified in two patients. These results demonstrate that MFC is a reliable tool for an accurate diagnosis of the underlying hematologic disease in patients with AL amyloidosis.

from Cancer via ola Kala on Inoreader http://ift.tt/24eEDek
via IFTTT

Adherence to cancer screening guidelines in Australian survivors of allogeneic blood and marrow transplantation (BMT)

Abstract

Allogeneic Blood and Marrow Transplant (BMT) survivors are at high risk of secondary cancers. Although current guidelines endorse survivors following Country-specific general population screening recommendations to mitigate this risk, little is known about cancer screening adherence in Australian BMT survivors. We conducted a cross-sectional survey of 441 BMT survivors who were >1 year post transplant, to explore rates of screening for secondary cancers and to identify barriers to cancer screening recommendations. Survey instruments included the Sydney Post-BMT Survey, FACT-BMT, DASS 21, The Chronic Graft versus Host Disease (GVHD) Activity Assessment–Patient Self-Report (Form B), the Lee Chronic GVHD Symptom Scale, Fear of Cancer Recurrence Scale, and The Post Traumatic Growth Inventory. Fifty-seven percent of respondents were male, median age 54 years, and 40% were >6 years post-BMT. Rates of cancer screening adherence were as follows: cervical 63.4%, breast 53.3%, skin 52.4%, and bowel 32.3%. Older BMT survivors and those >2 years post transplant were more likely to undergo cancer screening. Improved quality of life was associated with screening for skin, breast, and cervical cancer. Fear of cancer recurrence negatively impacted on cervical screening. For those who had not undergone screening, the majority reported not being advised to do so by their treatment team. This study is the largest and most comprehensive to date exploring cancer screening adherence in BMT survivors in Australia. These data provide the basis for health service reform to better meet the needs of BMT survivors and provide evidence to support counseling and education of both patients and professionals.

We conducted a cross-sectional survey of 441 Blood and Marrow Transplant (BMT) survivors who were >1 year post transplant, to explore rates of screening for secondary cancers and to identify barriers to adherence with cancer screening recommendations. Rates of cancer screening uptake were as follows: cervical 63.4%, breast 53.3%, skin 52.4%, and bowel 32.3%. Improved quality of life was associated with screening for skin, breast, and cervical cancer. Fear of cancer recurrence negatively impacted on cervical screening. For those who had not undergone screening, the majority reported not being advised to do so by their treatment team.

from Cancer via ola Kala on Inoreader http://ift.tt/1Wlfz2C
via IFTTT

Are parenting behaviors associated with child sleep problems during treatment for acute lymphoblastic leukemia?

Abstract

Sleep disturbance is a recognized common side effect in children treated for acute lymphoblastic leukemia (ALL). Although associated with treatment factors such as hospitalization and corticosteroids, sleep problems may also be influenced by modifiable environmental factors such as parenting behaviors. The purpose of this study was to examine sleep problems in children undergoing treatment for ALL compared to healthy children and whether parenting practices are associated with sleep difficulties. Parents of 73 children aged 2–6 years who were (1) in the maintenance phase of ALL treatment (ALL group, n = 43) or (2) had no major medical illness (healthy control group, n = 30) participated in the study. Parents completed questionnaires measuring their child's sleep behavior and their own parenting practices. Parents of children undergoing ALL treatment reported significantly more child sleep problems; 48% of children with ALL compared to 23% of healthy children had clinical levels of sleep disturbance. Parents of the ALL group also reported significantly more lax parenting practices and strategies associated with their child's sleep including co-sleeping, comforting activities, and offering food and drink in the bedroom. Results of multivariate regression analysis indicated that, after controlling for illness status, parent–child co-sleeping was significantly associated with child sleep difficulties. Strategies employed by parents during ALL treatment may be a potential modifiable intervention target that could result in improved child sleep behaviors. Future research aimed at developing and testing parenting interventions aimed to improve child sleep in the context of oncology treatment is warranted.

This study examined sleep problems in children undergoing treatment for acute lymphoblastic leukemia (ALL) compared to healthy children and whether parenting practices are associated with sleep difficulties. Parents of children with ALL reported significantly more child sleep problems and parent–child co-sleeping was significantly associated with child sleep difficulties. Strategies employed by parents during ALL treatment may be a potential modifiable intervention target that could result in improved child quality of life.

from Cancer via ola Kala on Inoreader http://ift.tt/24eEFDg
via IFTTT

Circulating CD14+HLA-DR-/low myeloid-derived suppressor cells in leukemia patients with allogeneic hematopoietic stem cell transplantation: novel clinical potential strategies for the prevention and cellular therapy of graft-versus-host disease

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that includes immature myeloid cells and the progenitor cells of macrophages, dendritic cells (DCs), monocytes, and neutrophils. The expansion and functional importance of MDSCs in patients with cancer and noncancer pathogenic conditions has been recognized. As a result, there has been growing interest in understanding their roles in acute graft-versus-host disease (aGVHD) after allogenetic hematopoietic stem cell transplantation (allo-HSCT). In order to evaluate possible effects of MDSCs on aGVHD development and clinical outcomes, this study systematically detected the dynamic changes of MDSCs accumulation in patients during the first 100 days after allo-HSCT, and investigated the levels of other cell types and relative cytokines during MDSCs accumulation. Results showed that accumulation of MDSCs in the graft and in peripheral blood when engraftment might contribute to patients' overall immune suppression and result in the successful control of severe aGVHD and long-term survival without influence on risk of recurrence after allo-HSCT. But MDSCs levels in the graft had more favorable predictive abilities. Furthermore, MDSCs proportion significantly increased in patients developing aGVHD after allo-HSCT. It might be caused by secondary inflammatory response, especially related to high concentrations of IL-6 and TNF-α. But this accumulation would not be able to counterbalance the aggravation of aGVHD and would not have influence on clinical outcomes and risk of relapse. Overall, MDSCs might be considered as potential new therapeutic option for aGVHD and achieve long-term immunological tolerance and survival.

This study revealed that MDSCs might be considered as a novel prognostic factor in patients with allo-HSCT and potential new approaches to regulate transplant rejection and achieve the recipient host long-term acceptance and survival. The understanding of the activation and differentiation of MDSCs in human will help to develop inhibitors during their unwanted activity, such as preventing relapse, but also provide options for therapeutical intervention in aGVHD after allo-HSCT.

from Cancer via ola Kala on Inoreader http://ift.tt/1Wlfyff
via IFTTT

Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas

Abstract

Identification of novel prognostic biomarkers typically requires a large dataset which provides sufficient statistical power for discovery research. To this end, we took advantage of the high-throughput data from The Cancer Genome Atlas (TCGA) to identify a set of prognostic biomarkers in head and neck squamous cell carcinomas (HNSCC) including oropharyngeal squamous cell carcinoma (OPSCC) and other subtypes. In this study, we analyzed miRNA-seq data obtained from TCGA patients to identify prognostic biomarkers for OPSCC. The identified miRNAs were further tested with an independent cohort. miRNA-seq data from TCGA was also analyzed to identify prognostic miRNAs in oral cavity squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC). Our study identified that miR-193b-3p and miR-455-5p were positively associated with survival, and miR-92a-3p and miR-497-5p were negatively associated with survival in OPSCC. A combined expression signature of these four miRNAs was prognostic of overall survival in OPSCC, and more importantly, this signature was validated in an independent OPSCC cohort. Furthermore, we identified four miRNAs each in OSCC and LSCC that were prognostic of survival, and combined signatures were specific for subtypes of HNSCC. A robust 4-miRNA prognostic signature in OPSCC, as well as prognostic signatures in other subtypes of HNSCC, was developed using sequencing data from TCGA as the primary source. This demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care.

Prognostic microRNA signatures were identified for head and neck cancers by analysis of public profiling data from The Cancer Genome Atlas (TCGA). This work demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care.

from Cancer via ola Kala on Inoreader http://ift.tt/24eECXS
via IFTTT

Phase II evaluation of sunitinib in the treatment of recurrent or refractory high-grade glioma or ependymoma in children: a children's Oncology Group Study ACNS1021

Abstract

Sunitinib malate is a small multi-targeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor (KIT), which are highly expressed by some high-grade brain tumors. We conducted a phase II study to estimate the efficacy and further characterize the pharmacokinetics of sunitinib in pediatric patients with recurrent or refractory high-grade glioma (Stratum A) or ependymoma (Stratum B). This was a prospective, multicenter Phase II trial conducted through the Children's Oncology Group (ClinicalTrials.gov Identifier NCT01462695). Sunitinib, 15 mg/m2, was orally administered once daily for 4 weeks every 6 weeks. The safety and tolerability of sunitinib, an estimate of progression-free survival (PFS), analyses of sunitinib pharmacokinetics (PK) and pharmacodynamics modulation of plasma VEGF and VEGFR2 were also assessed. Thirty eligible patients (17 patients on Stratum A, 13 patients on Stratum B) were enrolled and 29 patients were evaluable for response. Sunitinib was reasonably well tolerated in children with recurrent ependymoma or high-grade glioma. Most adverse events were of mild-to-moderate severity and manageable with supportive treatment. While there was a statistically significant modulation of plasma VEGFR2 with sunitinib exposure, there were no sustained tumor responses. Both strata were closed at time of planned interim analysis as there was not sufficient efficacy associated with sunitinib in children with recurrent brain tumors. Sunitinib was well tolerated in children and young adults with recurrent high-grade glioma or ependymoma but had no single agent objective antitumor activity in these patients.

This Phase II study of sunitinib reports the safety, tolerability and pharmacokinetic disposition in pediatric patients with recurrent high-grade glioma and ependymoma. While there was sufficient level of sunitinib in peripheral blood to modulate plasma vascular endothelial growth factor receptor (VEGFR)2, there were no sustained responses and no single agent activity in this patient cohort.

from Cancer via ola Kala on Inoreader http://ift.tt/1Wlfyf3
via IFTTT