Towards understanding the mechanisms of actions of CEACAM6 in cancer progression

Abstract

Human carcinoembryonic antigen (CEA) is the prototypic member of highly related cell surface glycoproteins that includes Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and others. CEACAM6 (formerly NCA) that belongs to the immunoglobulin superfamily, is a cell adhesion proteins of the CEA family. It is normally expressed on the epithelial surfaces and the surface of myeloid (CD66c). CEACAM6 is a multi-functional glycoprotein that mediates homotypic binding with other CEA family members and heterotypic binding with integrin receptors. It functions by organizing tissue architecture and regulating different signal transduction, while aberrant expression leads to the development of human malignancies. It was firstly discovered in proliferating cells of adenomas and hyperplastic polyps in comparison to benign colonic tissue when over-expressed on the surface of various cell types in model systems. CEACAM6, functions as a pan-inhibitor of cell differentiation and cell polarization, and it also cause distortion of tissue architecture. Moreover, over-expression of CEACAM6 modulates cancer progression through aberrant cell differentiation, anti-apoptosis, cell growth and resistance to therapeutic agents. In addition, CEACAM6 over-expression in multiple malignancies promoting cell invasion and metastasis thereby representing an acquired advantage of tumor cells directly responsible for an invasive phenotype. This review will focus on the findings supporting the mechanism of actions linking the oncogenic potential of CEACAM6 to the onset of cancer progression and pathogenesis specially in breast cancer, and to validate CEACAM6 as a target to pave the way towards the design of efficient therapeutic strategies against BC.

This article is protected by copyright. All rights reserved.

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Towards understanding the mechanisms of actions of CEACAM6 in cancer progression

Abstract

Human carcinoembryonic antigen (CEA) is the prototypic member of highly related cell surface glycoproteins that includes Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and others. CEACAM6 (formerly NCA) that belongs to the immunoglobulin superfamily, is a cell adhesion proteins of the CEA family. It is normally expressed on the epithelial surfaces and the surface of myeloid (CD66c). CEACAM6 is a multi-functional glycoprotein that mediates homotypic binding with other CEA family members and heterotypic binding with integrin receptors. It functions by organizing tissue architecture and regulating different signal transduction, while aberrant expression leads to the development of human malignancies. It was firstly discovered in proliferating cells of adenomas and hyperplastic polyps in comparison to benign colonic tissue when over-expressed on the surface of various cell types in model systems. CEACAM6, functions as a pan-inhibitor of cell differentiation and cell polarization, and it also cause distortion of tissue architecture. Moreover, over-expression of CEACAM6 modulates cancer progression through aberrant cell differentiation, anti-apoptosis, cell growth and resistance to therapeutic agents. In addition, CEACAM6 over-expression in multiple malignancies promoting cell invasion and metastasis thereby representing an acquired advantage of tumor cells directly responsible for an invasive phenotype. This review will focus on the findings supporting the mechanism of actions linking the oncogenic potential of CEACAM6 to the onset of cancer progression and pathogenesis specially in breast cancer, and to validate CEACAM6 as a target to pave the way towards the design of efficient therapeutic strategies against BC.

This article is protected by copyright. All rights reserved.

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Issue Information - Ed Board

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Functional Outcomes after De-Escalated Chemoradiation for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase II Trial

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): John V. Hegde, Narek Shaverdian, Carol Felix, Pin-Chieh Wang, Darlene Veruttipong, Sophia Hsu, Jonathan Riess, Shyam D. Rao, Megan E. Daly, Allen M. Chen
PurposeTo analyze functional outcomes for patients treated on a phase II trial of de-escalated chemoradiation for human papillomavirus (HPV)-positive oropharyngeal cancer.MethodsEligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma, and Zubrod performance status 0-1. Treatment was induction paclitaxel 175 mg/m² and carboplatin AUC 6 for 2 cycles every 21 days followed by concurrent paclitaxel 30 mg/m² every 7 days with dose-reduced radiation of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic utilization rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy-Head and Neck Scale.ResultsForty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed to be unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m²) pre-treatment, recovery back to baseline occurred at approximately 18 months (average BMI 23.2 vs. 22.3 kg/m², respectively, p=0.09). Two patients (5%) had gastrostomy tubes placed during treatment. No patient was enteral feeding tube dependent at 6 months post-treatment. Ninety-five percent tolerated a normal regular diet at last follow-up.ConclusionsDe-escalated chemoradiation may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation, BMI recovered to baseline levels.

Teaser

For patients with human papillomavirus (HPV)-associated oropharyngeal carcinoma undergoing chemoradiation with induction chemotherapy followed by de-escalated chemoradiation to 54 or 60 Gy with concurrent paclitaxel, functional outcomes, including nutritional status, gastrostomy tube use, dysphagia, and narcotic use, appear similar or favorable to historical controls treated with definitive chemoradiation to 70 Gy. These findings support ongoing efforts to evaluate de-escalated chemoradiation in patients with HPV-associated oropharyngeal carcinoma.


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PARP inhibition combined with thoracic radiation exacerbates esophageal and skin toxicity in C57BL6 mice

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Luiza Madia Lourenco, Yanyan Jiang, Neele Drobnitzky, Marcus Green, Fiona Cahill, Agata Patel, Yasmin Shanneik, John Moore, Anderson J. Ryan
PurposePARP inhibitors have been shown to enhance the radiosensitivity of cancer cells in vitro in a replication-dependent manner. Their in vivo radiosensitizing effects have also been demonstrated in preclinical tumor models. However, whether PARP inhibition can enhance the response to radiation in normal tissues has been largely neglected. We hypothesized that PARP inhibition might also potentiate the response of replicating normal tissues to radiation. In this study, we examined the normal tissue response in mice treated with PARP inhibitors (BMN673 or AZD2281) in combination with thoracic radiation.Methods and MaterialsAnti-tumor effects of fractionated radiation (5 Gy x 4) in combination with BMN673 were evaluated in nude mice bearing established Calu-6 human lung cancer xenografts. Normal tissue response was evaluated in C57BL6 mice that were treated with BMN673 or AZD2281 combined with fractionated 5 Gy x 4 radiation delivered to the whole thorax. Body weight and histology of the esophagus and skin in the field of irradiation were examined. DNA damage response in the esophagus and skin was assessed by γH2AX immunohistochemistry.ResultsWhilst PARP inhibition enhanced radiation-induced tumor growth inhibition in nude mice, it was also associated with significant body weight loss and increased damage to the esophagus and skin within the field of irradiation in C57BL6 mice. PARP inhibition compromised the repair of radiation-induced DNA damage in the esophagus and skin.ConclusionAlthough PARP inhibition enhanced the anti-tumor response to fractionated radiation, it also enhanced the radiation response in replicating normal tissues. Therefore, our study suggests that additional caution may be warranted in the clinical development of combination therapies utilizing PARP inhibitors and radiotherapy, in particular where the field of radiation includes the esophagus.

Teaser

PARP inhibitors have been demonstrated to potentiate the anti-tumor effect of radiation in preclinical studies. However, their effect on normal tissue response to radiation is unclear. Here we show that PARP inhibitors not only enhance radiation-induced tumor growth inhibition, but also enhance the response of the esophagus and skin to radiation. Therefore, caution may be warranted when combining PARP inhibition with radiotherapy that includes proliferating normal tissues.


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Low-dose hypersensitive response for residual pATM and γH2AX foci in normal fibroblasts of cancer patients

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Dorota Słonina, Aleksandra Kowalczyk, Anna Janecka-Widła, Damian Kabat, Wiktor Szatkowski, Beata Biesaga
PurposeIn our previous study, using flow cytometry-based clonogenic survival assay, we demonstrated low-dose hyper-radiosensitivity (HRS) effect in normal fibroblasts of 4 of the 25 cancer patients investigated. In the present study, we define the dose-response relationship for initial and residual pATM and γH2AX foci and temporal response of pATM foci in fibroblasts of the 4 HRS-positive patients and 8 HRS-negative patients and answer the question regarding the role of DNA double strand break (DSB) recognition and repair in the mechanism of HRS.Methods and MaterialsThe cells were irradiated with single doses (0.1 - 4 Gy) of 6MV x-rays. The number of initial and residual pATM and γH2AX foci was assessed 1 hour and 24 hours after irradiation, respectively. Kinetics of DSB recognition and repair was estimated by pATM foci assay after irradiation with 0.2 and 2 Gy.ResultsHRS response (confirmed by the induced-repair model) was clearly evident for residual pATM and γH2AX foci in fibroblasts of HRS-positive patients, but not in fibroblasts of HRS-negative patients. Significantly less DSB was recognized by pATM early (10 – 30 minutes) after irradiation with 0.2 Gy in HRS-positive compared to HRS-negative fibroblasts.ConclusionsThe present results provide the evidence for the role of DSB recognition by pATM and repair in the mechanism of HRS and seem to support the idea of nucleoshuttling of the pATM protein to be involved in HRS response.

Teaser

We demonstrate, for the first time, low-dose hypersensitive response for both residual pATM and γH2AX foci in normal fibroblasts of 4 HRS-positive patients and its lack in fibroblasts of 8 HRS-negative patients. We also show that in HRS-positive fibroblasts not all DSB are recognized by pATM early after irradiation with low dose. The data provide the evidence for the role of DSB recognition by pATM and repair in the mechanism of HRS.


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Value of elective radiation oncology rotations: how many is too many?

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Samuel Jang, Stephen A. Rosenberg, Craig Hullet, Kristin A. Bradley, Randall J. Kimple




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Outcome after Radiotherapy for Langerhans Cell Histiocytosis Is Dependent on Site of Involvement

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): James Laird, Jennifer Ma, Karen Chau, Monica Chelius, Weiji Shi, Zhigang Zhang, Benjamin H. Lok, Joachim Yahalom
PurposeLangerhans cell histiocytosis (LCH) is a rare malignant disease characterized by histiocytic proliferation. We intended to characterize the efficacy and safety of radiation therapy (RT) in a contemporary cohort and to explore if there are sites at higher risk for local recurrence.Materials/MethodsBetween 1995 and 2015, we identified 39 consecutive LCH patients who were treated primarily with radiation therapy. Patients were staged by single/multisystem involvement (SS/MS) and established risk organ criteria. In 46 irradiated lesions, clinical and radiologic responses were evaluated at multiple time points after radiotherapy. Patient demographics, treatment, and local failure were compared by site of lesion.ResultsMedian age at RT was 35 years (range 1.5 – 67). Twelve patients had multisystem involvement, and of those, 5 patients had disease in organs considered to be high-risk. The following sites were irradiated: bone (31), brain (6), skin (3), lymph node (3), thyroid (2), and nasopharynx (1). Median dose was 11.4 Gy (7.5 – 50.4). At a median follow-up of 45 months (6 – 199), local recurrence or progression was noted in 5 of 46 (11%) lesions. There were no local failures of the 31 bone lesions evaluated, while the 3-year freedom from local failure in the 15 non-bone lesions was 63% (95% CI 32 – 83%; p = 0.0008). Local failures occurred in 2 of 3 skin lesions, in 2 of 6 brain lesions, and 1 of 3 lymph node lesions. Deaths were recorded in 5 of 39 (13%) patients, all of whom were adults with multisystem disease.ConclusionRadiotherapy is a safe and effective measure for providing local control of LCH involving the bone. While bone lesions are well controlled with low doses of radiation, disease in other tissues such as the skin and brain may require higher doses of radiation or additional treatment modalities.

Teaser

Langerhans cell histiocytosis is a rare histiocytic malignancy associated with a wide range of clinical presentations and outcomes. We explored treatment patterns and outcomes in a cohort of 39 patients with 46 radiation-treated lesions. We found the rate of local failure was significantly higher in patients with non-bone lesions, especially of the skin and brain, compared to excellent local control in bone lesions with relatively low doses of radiation.


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Functional Outcomes after De-Escalated Chemoradiation for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase II Trial

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): John V. Hegde, Narek Shaverdian, Carol Felix, Pin-Chieh Wang, Darlene Veruttipong, Sophia Hsu, Jonathan Riess, Shyam D. Rao, Megan E. Daly, Allen M. Chen
PurposeTo analyze functional outcomes for patients treated on a phase II trial of de-escalated chemoradiation for human papillomavirus (HPV)-positive oropharyngeal cancer.MethodsEligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma, and Zubrod performance status 0-1. Treatment was induction paclitaxel 175 mg/m² and carboplatin AUC 6 for 2 cycles every 21 days followed by concurrent paclitaxel 30 mg/m² every 7 days with dose-reduced radiation of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic utilization rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy-Head and Neck Scale.ResultsForty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed to be unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m²) pre-treatment, recovery back to baseline occurred at approximately 18 months (average BMI 23.2 vs. 22.3 kg/m², respectively, p=0.09). Two patients (5%) had gastrostomy tubes placed during treatment. No patient was enteral feeding tube dependent at 6 months post-treatment. Ninety-five percent tolerated a normal regular diet at last follow-up.ConclusionsDe-escalated chemoradiation may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation, BMI recovered to baseline levels.

Teaser

For patients with human papillomavirus (HPV)-associated oropharyngeal carcinoma undergoing chemoradiation with induction chemotherapy followed by de-escalated chemoradiation to 54 or 60 Gy with concurrent paclitaxel, functional outcomes, including nutritional status, gastrostomy tube use, dysphagia, and narcotic use, appear similar or favorable to historical controls treated with definitive chemoradiation to 70 Gy. These findings support ongoing efforts to evaluate de-escalated chemoradiation in patients with HPV-associated oropharyngeal carcinoma.


http://ift.tt/2ybkc86

PARP inhibition combined with thoracic radiation exacerbates esophageal and skin toxicity in C57BL6 mice

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Luiza Madia Lourenco, Yanyan Jiang, Neele Drobnitzky, Marcus Green, Fiona Cahill, Agata Patel, Yasmin Shanneik, John Moore, Anderson J. Ryan
PurposePARP inhibitors have been shown to enhance the radiosensitivity of cancer cells in vitro in a replication-dependent manner. Their in vivo radiosensitizing effects have also been demonstrated in preclinical tumor models. However, whether PARP inhibition can enhance the response to radiation in normal tissues has been largely neglected. We hypothesized that PARP inhibition might also potentiate the response of replicating normal tissues to radiation. In this study, we examined the normal tissue response in mice treated with PARP inhibitors (BMN673 or AZD2281) in combination with thoracic radiation.Methods and MaterialsAnti-tumor effects of fractionated radiation (5 Gy x 4) in combination with BMN673 were evaluated in nude mice bearing established Calu-6 human lung cancer xenografts. Normal tissue response was evaluated in C57BL6 mice that were treated with BMN673 or AZD2281 combined with fractionated 5 Gy x 4 radiation delivered to the whole thorax. Body weight and histology of the esophagus and skin in the field of irradiation were examined. DNA damage response in the esophagus and skin was assessed by γH2AX immunohistochemistry.ResultsWhilst PARP inhibition enhanced radiation-induced tumor growth inhibition in nude mice, it was also associated with significant body weight loss and increased damage to the esophagus and skin within the field of irradiation in C57BL6 mice. PARP inhibition compromised the repair of radiation-induced DNA damage in the esophagus and skin.ConclusionAlthough PARP inhibition enhanced the anti-tumor response to fractionated radiation, it also enhanced the radiation response in replicating normal tissues. Therefore, our study suggests that additional caution may be warranted in the clinical development of combination therapies utilizing PARP inhibitors and radiotherapy, in particular where the field of radiation includes the esophagus.

Teaser

PARP inhibitors have been demonstrated to potentiate the anti-tumor effect of radiation in preclinical studies. However, their effect on normal tissue response to radiation is unclear. Here we show that PARP inhibitors not only enhance radiation-induced tumor growth inhibition, but also enhance the response of the esophagus and skin to radiation. Therefore, caution may be warranted when combining PARP inhibition with radiotherapy that includes proliferating normal tissues.


http://ift.tt/2zoF64X

Low-dose hypersensitive response for residual pATM and γH2AX foci in normal fibroblasts of cancer patients

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Dorota Słonina, Aleksandra Kowalczyk, Anna Janecka-Widła, Damian Kabat, Wiktor Szatkowski, Beata Biesaga
PurposeIn our previous study, using flow cytometry-based clonogenic survival assay, we demonstrated low-dose hyper-radiosensitivity (HRS) effect in normal fibroblasts of 4 of the 25 cancer patients investigated. In the present study, we define the dose-response relationship for initial and residual pATM and γH2AX foci and temporal response of pATM foci in fibroblasts of the 4 HRS-positive patients and 8 HRS-negative patients and answer the question regarding the role of DNA double strand break (DSB) recognition and repair in the mechanism of HRS.Methods and MaterialsThe cells were irradiated with single doses (0.1 - 4 Gy) of 6MV x-rays. The number of initial and residual pATM and γH2AX foci was assessed 1 hour and 24 hours after irradiation, respectively. Kinetics of DSB recognition and repair was estimated by pATM foci assay after irradiation with 0.2 and 2 Gy.ResultsHRS response (confirmed by the induced-repair model) was clearly evident for residual pATM and γH2AX foci in fibroblasts of HRS-positive patients, but not in fibroblasts of HRS-negative patients. Significantly less DSB was recognized by pATM early (10 – 30 minutes) after irradiation with 0.2 Gy in HRS-positive compared to HRS-negative fibroblasts.ConclusionsThe present results provide the evidence for the role of DSB recognition by pATM and repair in the mechanism of HRS and seem to support the idea of nucleoshuttling of the pATM protein to be involved in HRS response.

Teaser

We demonstrate, for the first time, low-dose hypersensitive response for both residual pATM and γH2AX foci in normal fibroblasts of 4 HRS-positive patients and its lack in fibroblasts of 8 HRS-negative patients. We also show that in HRS-positive fibroblasts not all DSB are recognized by pATM early after irradiation with low dose. The data provide the evidence for the role of DSB recognition by pATM and repair in the mechanism of HRS.


http://ift.tt/2y9ifZD

Value of elective radiation oncology rotations: how many is too many?

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Samuel Jang, Stephen A. Rosenberg, Craig Hullet, Kristin A. Bradley, Randall J. Kimple




http://ift.tt/2znUP4s

Outcome after Radiotherapy for Langerhans Cell Histiocytosis Is Dependent on Site of Involvement

Publication date: Available online 6 November 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): James Laird, Jennifer Ma, Karen Chau, Monica Chelius, Weiji Shi, Zhigang Zhang, Benjamin H. Lok, Joachim Yahalom
PurposeLangerhans cell histiocytosis (LCH) is a rare malignant disease characterized by histiocytic proliferation. We intended to characterize the efficacy and safety of radiation therapy (RT) in a contemporary cohort and to explore if there are sites at higher risk for local recurrence.Materials/MethodsBetween 1995 and 2015, we identified 39 consecutive LCH patients who were treated primarily with radiation therapy. Patients were staged by single/multisystem involvement (SS/MS) and established risk organ criteria. In 46 irradiated lesions, clinical and radiologic responses were evaluated at multiple time points after radiotherapy. Patient demographics, treatment, and local failure were compared by site of lesion.ResultsMedian age at RT was 35 years (range 1.5 – 67). Twelve patients had multisystem involvement, and of those, 5 patients had disease in organs considered to be high-risk. The following sites were irradiated: bone (31), brain (6), skin (3), lymph node (3), thyroid (2), and nasopharynx (1). Median dose was 11.4 Gy (7.5 – 50.4). At a median follow-up of 45 months (6 – 199), local recurrence or progression was noted in 5 of 46 (11%) lesions. There were no local failures of the 31 bone lesions evaluated, while the 3-year freedom from local failure in the 15 non-bone lesions was 63% (95% CI 32 – 83%; p = 0.0008). Local failures occurred in 2 of 3 skin lesions, in 2 of 6 brain lesions, and 1 of 3 lymph node lesions. Deaths were recorded in 5 of 39 (13%) patients, all of whom were adults with multisystem disease.ConclusionRadiotherapy is a safe and effective measure for providing local control of LCH involving the bone. While bone lesions are well controlled with low doses of radiation, disease in other tissues such as the skin and brain may require higher doses of radiation or additional treatment modalities.

Teaser

Langerhans cell histiocytosis is a rare histiocytic malignancy associated with a wide range of clinical presentations and outcomes. We explored treatment patterns and outcomes in a cohort of 39 patients with 46 radiation-treated lesions. We found the rate of local failure was significantly higher in patients with non-bone lesions, especially of the skin and brain, compared to excellent local control in bone lesions with relatively low doses of radiation.


http://ift.tt/2yaMPSP

Management of organ motion in scanned ion beam therapy

Scanned ion beam therapy has special demands for treatment of intra-fractionally moving tumors such as lesions in lung or liver. Interplay effects between beam and organ motion can in those settings lead to un...

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Multicriteria plan optimization in the hands of physicians: a pilot study in prostate cancer and brain tumors

The purpose of this study was to demonstrate the feasibility of physician driven planning in intensity modulated radiotherapy (IMRT) with a multicriteria optimization (MCO) treatment planning system and templa...

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Clinical outcomes of graves’ ophthalmopathy treated with intensity modulated radiation therapy

Radiation for Graves' ophthalmopathy (GO) has traditionally utilized lateral opposing fields (LOF) or three-dimensional conformal radiotherapy (3DCRT) technique. The current study was conducted to report clini...

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First intraindividual comparison of contrast-enhanced MRI, FET- and DOTATOC- PET in patients with intracranial meningiomas

For irradiation treatment planning of meningiomas the use of PET-scans is well established. The most frequently used tracers are either based on amino acids or the somatostatin receptor ligand DOTATOC. Since u...

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Normal lung sparing Tomotherapy technique in stage III lung cancer

Radiation pneumonitis (RP) has been a challenging obstacle in treating stage III lung cancer patients. Beam angle optimization (BAO) technique for Tomotherapy was developed to reduce the normal lung dose for s...

http://ift.tt/2yc9rCc

Multicriteria plan optimization in the hands of physicians: a pilot study in prostate cancer and brain tumors

The purpose of this study was to demonstrate the feasibility of physician driven planning in intensity modulated radiotherapy (IMRT) with a multicriteria optimization (MCO) treatment planning system and templa...

http://ift.tt/2zmnIOa

Clinical outcomes of graves’ ophthalmopathy treated with intensity modulated radiation therapy

Radiation for Graves' ophthalmopathy (GO) has traditionally utilized lateral opposing fields (LOF) or three-dimensional conformal radiotherapy (3DCRT) technique. The current study was conducted to report clini...

http://ift.tt/2yaf8AE

First intraindividual comparison of contrast-enhanced MRI, FET- and DOTATOC- PET in patients with intracranial meningiomas

For irradiation treatment planning of meningiomas the use of PET-scans is well established. The most frequently used tracers are either based on amino acids or the somatostatin receptor ligand DOTATOC. Since u...

http://ift.tt/2zmDQPU

TAGLN2 is a candidate prognostic biomarker promoting tumorigenesis in human gliomas

Transgelin-2 (TAGLN2) is a member of the calponin family of actin-bundling proteins that is involved in the regulation of cell morphology, motility, and cell transformation. Here, the clinical significance and...

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Chemoprevention with Cyclooxygenase and Epidermal Growth Factor Receptor Inhibitors in Familial Adenomatous Polyposis Patients: mRNA Signatures of Duodenal Neoplasia

To identify gene expression biomarkers and pathways targeted by sulindac and erlotinib given in a chemoprevention trial with a significant decrease in duodenal polyp burden at 6 months (P < 0.001) in familial adenomatous polyposis (FAP) patients, we biopsied normal and polyp duodenal tissues from patients on drug versus placebo and analyzed the RNA expression. RNA sequencing was performed on biopsies from the duodenum of FAP patients obtained at baseline and 6-month endpoint endoscopy. Ten FAP patients on placebo and 10 on sulindac and erlotinib were selected for analysis. Purity of biopsied polyp tissue was calculated from RNA expression data. RNAs differentially expressed between endpoint polyp and paired baseline normal were determined for each group and mapped to biological pathways. Key genes in candidate pathways were further validated by quantitative RT-PCR. RNA expression analyses of endpoint polyp compared with paired baseline normal for patients on placebo and drug show that pathways activated in polyp growth and proliferation are blocked by this drug combination. Directly comparing polyp gene expression between patients on drug and placebo also identified innate immune response genes (IL12 and IFN) preferentially expressed in patients on drug. Gene expression analyses from tissue obtained at endpoint of the trial demonstrated inhibition of the cancer pathways COX2/PGE2, EGFR, and WNT. These findings provide molecular evidence that the drug combination of sulindac and erlotinib reached the intended tissue and was on target for the predicted pathways. Furthermore, activation of innate immune pathways from patients on drug may have contributed to polyp regression. Cancer Prev Res; 1–12. ©2017 AACR.

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Circling Back for the Diagnosis

Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage. A 28-year-old man presented to the…

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Case 33-2017: 22-Month-Old Conjoined Twins

Presentation of Case. Dr. Allan M. Goldstein: A pediatric surgeon at this hospital was contacted by a nonprofit organization to evaluate the possibility of surgical separation of conjoined twin girls. The twins were born by spontaneous vaginal delivery in East Africa. Because of the anticipated…

http://ift.tt/2iBnQ4o

Post-radiochemotherapy PET radiomics in head and neck cancer – The influence of radiomics implementation on the reproducibility of local control tumor models

This study investigated an association of post-radiochemotherapy (RCT) PET radiomics with local tumor control in head and neck squamous cell carcinoma (HNSCC) and evaluated the models against two radiomics software implementations.

http://ift.tt/2yCAdba

With or without consolidation chemotherapy using cisplatin/5-FU after concurrent chemoradiotherapy in stage II–III squamous cell carcinoma of the esophagus: A propensity score-matched analysis

The benefit of consolidation chemotherapy for locally advanced squamous cell carcinoma of the esophagus is unknown. The aim of this study was to investigate the efficacy of consolidation chemotherapy with cisplatin and 5-fluorouracil (5-FU) after concurrent chemoradiotherapy (CCRT) with the same agents in patients with stage II–III disease.

http://ift.tt/2lZ6CD6

Association between treatment planning and delivery factors and disease progression in prostate cancer radiotherapy: Results from the TROG 03.04 RADAR trial

To evaluate the impact of treatment planning and delivery factors on treatment outcome as measured by post-treatment disease progression.

http://ift.tt/2yAR3az

Prognostic impact of RITA expression in patients with anal squamous cell carcinoma treated with chemoradiotherapy

RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive.

http://ift.tt/2lUULpq

Ventilation measured on clinical 4D-CBCT: Increased ventilation accuracy through improved image quality

Ventilation measured on 4D cone-beam computed tomography (CBCT) using deformable image registration (DIR) may predict specific radiation sensitivity, but the measurement is affected by the current image quality. With 4D computed tomography (CT) measured ventilation acting as a gold standard the current study investigates if image improvements increase the accuracy of 4D-CBCT measured ventilation.

http://ift.tt/2lZEgbW

Clustering of multi-parametric functional imaging to identify high-risk subvolumes in non-small cell lung cancer

We aimed to identify tumour subregions with characteristic phenotypes based on pre-treatment multi-parametric functional imaging and correlate these subregions to treatment outcome. The subregions were created using imaging of metabolic activity (FDG-PET/CT), hypoxia (HX4-PET/CT) and tumour vasculature (DCE-CT).

http://ift.tt/2yCA1ss

Pneumomediastinum following a prolonged second stage of labor – an emphasis on early diagnosis and conservative management: a case report

Esophageal rupture is an extremely rare condition to occur to a pregnant or postnatal woman. Esophageal ruptures have been previously described in the literature; however, they are most common in the setting o...

http://ift.tt/2lYrTg1

Antiangiogenic therapy in breast cancer

Summary

Based on a strong rationale for anti-VEGF (vascular endothelial growth factor) treatment in breast cancer and promising preclinical data, great hopes have been placed on the anti-VEGF antibody bevacizumab. Clinical trials, however, reported conflicting results. In metastatic human epidermal growth factor receptor 2(HER2)-negative breast cancer, the addition of bevacizumab to standard chemotherapy improved consistently progression-free survival (PFS), however, without effect on overall survival (OS). In early breast cancer bevacizumab increased the pathologic complete response rate (pCR) after neoadjuvant therapy, but adjuvant trials did not demonstrate an effect on long-term survival. Unfortunately, despite extensive research, there is still no biomarker for bevacizumab efficacy available, making patient selection difficult. This review summarizes all phase III trials investigating efficacy and toxicity of bevacizumab in early, locally advanced and metastatic breast cancer. It recapitulates the main toxicities, gives an overview on biomarker studies and discusses the role and future aspects of antiangiogenic therapy in breast cancer.

http://ift.tt/2j44Hfl

Antiangiogenic therapy in breast cancer

Summary

Based on a strong rationale for anti-VEGF (vascular endothelial growth factor) treatment in breast cancer and promising preclinical data, great hopes have been placed on the anti-VEGF antibody bevacizumab. Clinical trials, however, reported conflicting results. In metastatic human epidermal growth factor receptor 2(HER2)-negative breast cancer, the addition of bevacizumab to standard chemotherapy improved consistently progression-free survival (PFS), however, without effect on overall survival (OS). In early breast cancer bevacizumab increased the pathologic complete response rate (pCR) after neoadjuvant therapy, but adjuvant trials did not demonstrate an effect on long-term survival. Unfortunately, despite extensive research, there is still no biomarker for bevacizumab efficacy available, making patient selection difficult. This review summarizes all phase III trials investigating efficacy and toxicity of bevacizumab in early, locally advanced and metastatic breast cancer. It recapitulates the main toxicities, gives an overview on biomarker studies and discusses the role and future aspects of antiangiogenic therapy in breast cancer.

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Extraordinary clinical benefit to sequential treatment with targeted therapy and immunotherapy of a BRAF V600E and PD-L1 positive metastatic lung adenocarcinoma

Abstract

Background

The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression.

Case presentation

We present a case of 74-year-old female, former smoker with metastatic lung adenocarcinoma. The BRAF V600E mutation among other abnormalities was identified by comprehensive genomic profiling. The patient had an excellent 2-year response to the combination of pemetrexed and sorafenib. The patient was then treated with dabrafenib due to the presence of the BRAF V600E mutation and intolerance to cytotoxic chemotherapy. Not only the patient had an 18-month durable response to dabrafenib, she experienced outstanding quality of life with no serious adverse effects. At the time of symptomatic progression, the patient was then treated with two cycles of pembrolizumab based on her positive PD-L1 staining (90%). She had early response and came off pembrolizumab due to side effects. Seven months after initiation of pembrolizumab, the patient is off all the therapy and is currently asymptomatic. The patient is surviving with metastatic disease for over 7 years as of to date.

Conclusions

By appropriately sequencing the three main modalities of systemic therapies, we are able to achieve long-term disease control with minimal side effects even in a geriatric patient with multiple comorbidities. We argue that it is reasonable to first use a BRAF inhibitor before considering immunotherapy for NSCLCs positive for both BRAF V600E and PD-L1.

http://ift.tt/2zBihOi

Extraordinary clinical benefit to sequential treatment with targeted therapy and immunotherapy of a BRAF V600E and PD-L1 positive metastatic lung adenocarcinoma

Abstract

Background

The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression.

Case presentation

We present a case of 74-year-old female, former smoker with metastatic lung adenocarcinoma. The BRAF V600E mutation among other abnormalities was identified by comprehensive genomic profiling. The patient had an excellent 2-year response to the combination of pemetrexed and sorafenib. The patient was then treated with dabrafenib due to the presence of the BRAF V600E mutation and intolerance to cytotoxic chemotherapy. Not only the patient had an 18-month durable response to dabrafenib, she experienced outstanding quality of life with no serious adverse effects. At the time of symptomatic progression, the patient was then treated with two cycles of pembrolizumab based on her positive PD-L1 staining (90%). She had early response and came off pembrolizumab due to side effects. Seven months after initiation of pembrolizumab, the patient is off all the therapy and is currently asymptomatic. The patient is surviving with metastatic disease for over 7 years as of to date.

Conclusions

By appropriately sequencing the three main modalities of systemic therapies, we are able to achieve long-term disease control with minimal side effects even in a geriatric patient with multiple comorbidities. We argue that it is reasonable to first use a BRAF inhibitor before considering immunotherapy for NSCLCs positive for both BRAF V600E and PD-L1.

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Role of Platinum in Early-Stage Triple-Negative Breast Cancer

Opinion statement

Triple-negative breast cancer (TNBC) is both a clinically and genomically heterogeneous disease, with distinct molecular subtypes; however, most epidemiologic and clinical studies to date have defined it under a "one disease" umbrella. This is an important point, since one therapeutic approach for all TNBCs is unlikely to be successful given the underlying biological diversity. In this review, we explore the role of platinums in the treatment of TNBC, as well as the potential for biomarkers to predict patient response to these agents. The results of neoadjuvant TNBC trials, with addition of platinum to anthracycline/taxane-based chemotherapies, have been very encouraging given increases in pathologic complete response (pCR) rates. However, we do not have any evidence yet that these agents would lead to improvement in disease-free and overall survival. Moreover, addition of platinums increases toxicity and can compromise current standard chemotherapy doses, which further impedes their use in all TNBC patients. Therefore, the addition of platinums to standard chemotherapy should be used with caution and in discussion with patients after a careful assessment of risks and benefits. Clinical trials addressing the role of platinums in TNBC further remain of significant value.

http://ift.tt/2zByHpX

Role of Platinum in Early-Stage Triple-Negative Breast Cancer

Opinion statement

Triple-negative breast cancer (TNBC) is both a clinically and genomically heterogeneous disease, with distinct molecular subtypes; however, most epidemiologic and clinical studies to date have defined it under a "one disease" umbrella. This is an important point, since one therapeutic approach for all TNBCs is unlikely to be successful given the underlying biological diversity. In this review, we explore the role of platinums in the treatment of TNBC, as well as the potential for biomarkers to predict patient response to these agents. The results of neoadjuvant TNBC trials, with addition of platinum to anthracycline/taxane-based chemotherapies, have been very encouraging given increases in pathologic complete response (pCR) rates. However, we do not have any evidence yet that these agents would lead to improvement in disease-free and overall survival. Moreover, addition of platinums increases toxicity and can compromise current standard chemotherapy doses, which further impedes their use in all TNBC patients. Therefore, the addition of platinums to standard chemotherapy should be used with caution and in discussion with patients after a careful assessment of risks and benefits. Clinical trials addressing the role of platinums in TNBC further remain of significant value.

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Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells

Abstract

Background

Cancer stem cells (CSCs) are considered to be the major factor in tumor initiation, progression, metastasis, recurrence and chemoresistance. Maintaining the stemness and promoting differentiation of these cells involve various factors. Recently, long non-coding RNAs (lncRNAs) have been identified as new regulatory factors in human cancer cells. However, the function of lncRNAs in colon CSCs is still unknown.

Methods

Primary colon cancer cells were maintained in serum-free medium to form spheres and CD133⁺/CD166⁺/CD44⁺ spheroid cells were selected using FACS technique. Then we detected growth curve, colony formation, invasion and migration ability, and tumorigenicity of CD133⁺/CD166⁺/CD44⁺ cells. LOCCS-siRNA and pcDNA-LOCCS plasmid vectors were constructed and transfected to evaluate impact of the lncRNA. We also performed dual luciferase reporter assay to verify the interaction of LOCCS and miR-93.

Results

The research explored lncRNA expression and the regulatory role of novel lncRNAs in colon CSCs. Using the stem cell markers CD133, CD166 and CD44, we found a subpopulation of highly tumorigenic human colon cancer cells. They displayed some characteristics of stem cells, including the ability to proliferate and form colonies, to resist chemotherapeutic drugs, and to produce xenografts in nude mice. We also found an lncRNA, LOCCS, with obviously upregulated expression in colon CSCs. Knockdown of LOCCS reduced cell proliferation, invasion, migration, and generation of tumor xenografts. Furthermore, microRNA-93 (miR-93) and Musashi-1 mediated the tumor suppression of LOCCS knockdown.

Conclusions

There was reciprocal repression between LOCCS and miR-93. Research on mechanisms suggested direct binding, as a predicted miR-93 binding site was identified in LOCCS. This comprehensive analysis of LOCCS in colon CSCs provides insight for elucidating important roles of the lncRNA–microRNA functional network in human colon cancer.

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Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells

Abstract

Background

Cancer stem cells (CSCs) are considered to be the major factor in tumor initiation, progression, metastasis, recurrence and chemoresistance. Maintaining the stemness and promoting differentiation of these cells involve various factors. Recently, long non-coding RNAs (lncRNAs) have been identified as new regulatory factors in human cancer cells. However, the function of lncRNAs in colon CSCs is still unknown.

Methods

Primary colon cancer cells were maintained in serum-free medium to form spheres and CD133⁺/CD166⁺/CD44⁺ spheroid cells were selected using FACS technique. Then we detected growth curve, colony formation, invasion and migration ability, and tumorigenicity of CD133⁺/CD166⁺/CD44⁺ cells. LOCCS-siRNA and pcDNA-LOCCS plasmid vectors were constructed and transfected to evaluate impact of the lncRNA. We also performed dual luciferase reporter assay to verify the interaction of LOCCS and miR-93.

Results

The research explored lncRNA expression and the regulatory role of novel lncRNAs in colon CSCs. Using the stem cell markers CD133, CD166 and CD44, we found a subpopulation of highly tumorigenic human colon cancer cells. They displayed some characteristics of stem cells, including the ability to proliferate and form colonies, to resist chemotherapeutic drugs, and to produce xenografts in nude mice. We also found an lncRNA, LOCCS, with obviously upregulated expression in colon CSCs. Knockdown of LOCCS reduced cell proliferation, invasion, migration, and generation of tumor xenografts. Furthermore, microRNA-93 (miR-93) and Musashi-1 mediated the tumor suppression of LOCCS knockdown.

Conclusions

There was reciprocal repression between LOCCS and miR-93. Research on mechanisms suggested direct binding, as a predicted miR-93 binding site was identified in LOCCS. This comprehensive analysis of LOCCS in colon CSCs provides insight for elucidating important roles of the lncRNA–microRNA functional network in human colon cancer.

http://ift.tt/2lYqdU3

The prognostic role of epigenetic dysregulation in bladder cancer: A systematic review

Publication date: December 2017
Source:Cancer Treatment Reviews, Volume 61
Author(s): David Casadevall, Anaïs Yacine Kilian, Joaquim Bellmunt
BackgroundDespite adequate treatment and follow-up, around one fifth of patients with localized bladder cancer will present with disease progression. Adequate prognostic biomarkers are lacking to define patients who are at risk. Mutations in chromatin remodeling genes are more frequently found in bladder cancer than in any other solid tumor. However, the prognostic relevance of epigenetic dysregulation has not been established and may offer an opportunity for biomarker discovery.MethodsLooking for prognostic epigenetic factors, we performed a comprehensive PubMed search using keywords such as "bladder cancer", "chromatin remodeling", "gene methylation" and "epigenetics". We only included studies reporting on the association of epigenetic markers with prognostic outcomes such as recurrence, progression or survival.ResultsOf 1113 results, 87 studies met the inclusion criteria, which represented a total of 85 epigenetic markers with potential prognostic relevance. No prospective studies were identified. Seventy-three percent (64/87) of the studies involved mixed cohorts of muscle invasive and non-muscle invasive bladder cancer. Promoter methylation of genes with putative prognostic value affected cellular processes such as cell cycle, apoptosis, cell-adhesion or migration, as well as critical pathways such as MAP-kinase or Wnt. Alteration of chromatin regulatory elements suggest a prognostic relevance alterations leading to a predominantly silenced chromatin state.ConclusionsThe prognostic impact of epigenetic alterations in bladder cancer is still unclear. Prospective evaluation of methylation marks and chromatin remodeling gene alterations using consistent methods and criteria is warranted.



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Systematic review of the clinical and economic value of gene expression profiles for invasive early breast cancer available in Europe

Publication date: Available online 6 November 2017
Source:Cancer Treatment Reviews
Author(s): E.J. Blok, E. Bastiaannet, W.B. van den Hout, G.J. Liefers, V.T.H.B.M. Smit, J.R. Kroep, C.J.H. van de Velde
Gene expression profiles with prognostic capacities have shown good performance in multiple clinical trials. However, with multiple assays available and numerous types of validation studies performed, the added value for daily clinical practice is still unclear. In Europe, the MammaPrint, OncotypeDX, PAM50/Prosigna and Endopredict assays are commercially available. In this systematic review, we aim to assess these assays on four important criteria: Assay development and methodology, clinical validation, clinical utility and economic value.We performed a literature search covering PubMed, Embase, Web of Science and Cochrane, for studies related to one or more of the four selected assays.We identified 147 papers for inclusion in this review. MammaPrint and OncotypeDX both have evidence available, including level IA clinical trial results for both assays. Both assays provide prognostic information. Predictive value has only been shown for OncotypeDX. In the clinical utility studies, a higher reduction in chemotherapy was achieved by OncotypeDX, although the number of available studies differ considerably between tests. On average, economic evaluations estimate that genomic testing results in a moderate increase in total costs, but that these costs are acceptable in relation to the expected improved patient outcome. PAM50/prosigna and EndoPredict showed comparable prognostic capacities, but with less economical and clinical utility studies. Furthermore, for these assays no level IA trial data are available yet.In summary, all assays have shown excellent prognostic capacities. The differences in the quantity and quality of evidence are discussed. Future studies shall focus on the selection of appropriate subgroups for testing and long-term outcome of validation trials, in order to determine the place of these assays in daily clinical practice.



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Levels of Immune Cells within Ovarian Tumors Linked to Survival for Some Patients

A large international study suggests that the presence of certain immune cells within the tumors of some patients with ovarian cancer are associated with improved survival.

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Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis

Abstract

Purpose

Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM–HCC.

Methods

Synchronous PM–HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE.

Results

Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338).

Conclusions

Prognosis of synchronous PM–HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.

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Levels of Immune Cells within Ovarian Tumors Linked to Survival for Some Patients

A large international study suggests that the presence of certain immune cells within the tumors of some patients with ovarian cancer are associated with improved survival.

http://ift.tt/2zmkCKc

Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis

Abstract

Purpose

Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM–HCC.

Methods

Synchronous PM–HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE.

Results

Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338).

Conclusions

Prognosis of synchronous PM–HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.

http://ift.tt/2znEa0V

Characterization of hormonal receptors and human epidermal growth factor receptor-2 in tissues of women with breast cancer at Muhimbili National Hospital, Dar es salaam, Tanzania

Abstract

Background

Breast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu) expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH).

Methods

A cross-sectional study of female breast post-modified radical mastectomy (MRM)/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January–December 2013). Tissue blocks having poor morphology, without tumor, secondary tumors, cases outside the study period and male patients were excluded. Routine staining was done followed by immunohistochemistry for estrogen (ER), and progesterone (PgR) receptors and HER2. Data analyzed using Statistical Package for Social Sciences (SPSS).

Results

A total of 218 cases were confirmed to be carcinoma including 70 meeting inclusion criteria. Age at diagnosis ranged 18–75 years and mean age was 48.36 years. Majority (64.3%) were in the 36–55 years age-group. Histologically, most (88.6%) women had invasive ductal carcinoma including 43.1% of intermediate grade. A great majority (78%) were stage three. Due to logistical constrains, 75.7% (n = 53/70) cases where immunostained for hormones including 43.4% (ER+), 26.4% (PgR+), and 28% (ER+/PgR+). Furthermore, 65.7% (n = 46/70) cases were immunostained for HER-2 and 15.2% (n = 7/46) were positive, 45.6% were triple negative (ER-,PgR-,HER2-), 23.9% (ER+,PgR+,HER2-) or luminal B, 2.2% (ER+,PgR-,HER2+),13% (ER-,PgR-,HER2+) and 15% (ER+,PgR-,HER2-) with none being triple positive.

Conclusions

Hormonal receptors and HER2 expression at MNH appears to be comparable to previous Africans/African Americans reports but not with studies among Caucasians and the current proportion of triple negative breast carcinomas (TNBC) is higher than in a previous Tanzanian report and majority are luminal. HER2 over-expression is relatively common. It is strongly recommended that receptor status assessment be made routine for breast cancer patients at MNH.

http://ift.tt/2hLXih8

Characterization of hormonal receptors and human epidermal growth factor receptor-2 in tissues of women with breast cancer at Muhimbili National Hospital, Dar es salaam, Tanzania

Abstract

Background

Breast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu) expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH).

Methods

A cross-sectional study of female breast post-modified radical mastectomy (MRM)/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January–December 2013). Tissue blocks having poor morphology, without tumor, secondary tumors, cases outside the study period and male patients were excluded. Routine staining was done followed by immunohistochemistry for estrogen (ER), and progesterone (PgR) receptors and HER2. Data analyzed using Statistical Package for Social Sciences (SPSS).

Results

A total of 218 cases were confirmed to be carcinoma including 70 meeting inclusion criteria. Age at diagnosis ranged 18–75 years and mean age was 48.36 years. Majority (64.3%) were in the 36–55 years age-group. Histologically, most (88.6%) women had invasive ductal carcinoma including 43.1% of intermediate grade. A great majority (78%) were stage three. Due to logistical constrains, 75.7% (n = 53/70) cases where immunostained for hormones including 43.4% (ER+), 26.4% (PgR+), and 28% (ER+/PgR+). Furthermore, 65.7% (n = 46/70) cases were immunostained for HER-2 and 15.2% (n = 7/46) were positive, 45.6% were triple negative (ER-,PgR-,HER2-), 23.9% (ER+,PgR+,HER2-) or luminal B, 2.2% (ER+,PgR-,HER2+),13% (ER-,PgR-,HER2+) and 15% (ER+,PgR-,HER2-) with none being triple positive.

Conclusions

Hormonal receptors and HER2 expression at MNH appears to be comparable to previous Africans/African Americans reports but not with studies among Caucasians and the current proportion of triple negative breast carcinomas (TNBC) is higher than in a previous Tanzanian report and majority are luminal. HER2 over-expression is relatively common. It is strongly recommended that receptor status assessment be made routine for breast cancer patients at MNH.

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Role of Platinum in Early-Stage Triple-Negative Breast Cancer

Opinion statement

Triple-negative breast cancer (TNBC) is both a clinically and genomically heterogeneous disease, with distinct molecular subtypes; however, most epidemiologic and clinical studies to date have defined it under a "one disease" umbrella. This is an important point, since one therapeutic approach for all TNBCs is unlikely to be successful given the underlying biological diversity. In this review, we explore the role of platinums in the treatment of TNBC, as well as the potential for biomarkers to predict patient response to these agents. The results of neoadjuvant TNBC trials, with addition of platinum to anthracycline/taxane-based chemotherapies, have been very encouraging given increases in pathologic complete response (pCR) rates. However, we do not have any evidence yet that these agents would lead to improvement in disease-free and overall survival. Moreover, addition of platinums increases toxicity and can compromise current standard chemotherapy doses, which further impedes their use in all TNBC patients. Therefore, the addition of platinums to standard chemotherapy should be used with caution and in discussion with patients after a careful assessment of risks and benefits. Clinical trials addressing the role of platinums in TNBC further remain of significant value.

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The Significance of Long Non-coding RNA HULC in Predicting Prognosis and Metastasis of Cancers: a Meta-Analysis

Abstract

Long non-coding RNAs (lncRNAs) have been demonstrated that they not only play important roles in tumorgenicity but also associate with cancer prognosis. Recently, highly up-regulated in liver cancer (HULC) is abnormally expressed in liver cancer and other cancers, and participated in cancers progression; however, it is unclear whether its expression is associated with prognosis. Here, we performed a meta-analysis and systematic review to evaluate the prognostic value and metastasis of HULC in various cancer patients. The meta-analysis was performed using a systematic search of PubMed, Web of Science, ScienceDirect and Wiley Online Library database to eligible studies. The pooled hazard ratios (HRs) with a 95% confidence interval (95% CI) were calculated to assess its prognosis and metastasis in human cancer. A total of 1134 patients from 11 studies were included. The results indicated that overexpression of HULC was associated with poor overall survival (OS) (HR = 1.89, 95% CI: 1.32–2.47). Furthermore, subgroup analysis showed that cancer type (digestive system cancer or non-digestive system cancers) and sample size (more or less than 100) significantly associated between HULC and OS. In addition, overexpression of HULC expression was significantly associated with metastasis in cancers (HR = 2.67, 95% CI: 0.94–4.39). The meta-analysis indicated that lncRNA HULC could serve as a new molecular marker for cancer prognosis and metastasis.

http://ift.tt/2izomQu

Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis

Abstract

Purpose

Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM–HCC.

Methods

Synchronous PM–HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE.

Results

Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338).

Conclusions

Prognosis of synchronous PM–HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.

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The Significance of Long Non-coding RNA HULC in Predicting Prognosis and Metastasis of Cancers: a Meta-Analysis

Abstract

Long non-coding RNAs (lncRNAs) have been demonstrated that they not only play important roles in tumorgenicity but also associate with cancer prognosis. Recently, highly up-regulated in liver cancer (HULC) is abnormally expressed in liver cancer and other cancers, and participated in cancers progression; however, it is unclear whether its expression is associated with prognosis. Here, we performed a meta-analysis and systematic review to evaluate the prognostic value and metastasis of HULC in various cancer patients. The meta-analysis was performed using a systematic search of PubMed, Web of Science, ScienceDirect and Wiley Online Library database to eligible studies. The pooled hazard ratios (HRs) with a 95% confidence interval (95% CI) were calculated to assess its prognosis and metastasis in human cancer. A total of 1134 patients from 11 studies were included. The results indicated that overexpression of HULC was associated with poor overall survival (OS) (HR = 1.89, 95% CI: 1.32–2.47). Furthermore, subgroup analysis showed that cancer type (digestive system cancer or non-digestive system cancers) and sample size (more or less than 100) significantly associated between HULC and OS. In addition, overexpression of HULC expression was significantly associated with metastasis in cancers (HR = 2.67, 95% CI: 0.94–4.39). The meta-analysis indicated that lncRNA HULC could serve as a new molecular marker for cancer prognosis and metastasis.

http://ift.tt/2izomQu

Correction to: Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma

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Correction to: Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma

http://ift.tt/2yzqTEZ

Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis

Abstract

Purpose

Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM–HCC.

Methods

Synchronous PM–HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE.

Results

Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338).

Conclusions

Prognosis of synchronous PM–HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.

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Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis

Abstract

Purpose

Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM–HCC.

Methods

Synchronous PM–HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE.

Results

Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338).

Conclusions

Prognosis of synchronous PM–HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.

http://ift.tt/2znEa0V

Postoperative survival of EGFR-TKI-targeted therapy in non-small cell lung cancer patients with EGFR 19 or 21 mutations: a retrospective study

Abstract

Background

The aim of this retrospective study is to identify epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer patients and to compare the long-term postoperative outcomes in different EGFR-TKI-targeted therapy effects between the different EGFR mutation groups.

Methods

A total of 2094 postoperative non-small cell lung cancer (NSCLC) patients with EGFR gene detection were collected in the Department of Pathology in the Cancer Hospital Chinese Academy of Medical Sciences from January 2003 to January 2014. Three hundred sixty-three patients were treated with EGFR tyrosine kinase inhibitor (TKI) after surgery: 184 harbored the exon 19 deletion mutation and 179 cases carried the exon 21 L858R point mutation. The end points included progression-free survival (PFS), overall survival (OS), and the response rate.

Results

OS was increased in the EGFR exon 19 deletion group compared with the exon 21 L858R point mutation group (92 vs. 65 months; P < 0.001). But the median PFS did not differ between two groups (12 vs 14 months). The objective response rate (ORR) in 19 deletion group was increased compared with L858R mutation patients (28.35 vs. 22.73%). The disease control rate (DCR) of patients with 19 deletion benefited more from targeted therapy, compared with L858R group (93.71 vs. 84.31%, P = 0.014). In 19 deletion group, a high ORR and DCR were noted in patients treated with icotinib, 16 out of 18 achieved stable disease (SD), and the DCR in this population was 100%.

Conclusions

EGFR subtypes could influence the postoperative survival of NSCLC patients with TKI-targeted therapy.

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Residual microcalcifications after neoadjuvant chemotherapy for locally advanced breast cancer: comparison of the accuracies of mammography and MRI in predicting pathological residual tumor

Abstract

Background

The aims of this study were to correlate residual mammographic microcalcifications after neoadjuvant chemotherapy (NAC) with pathological results and to compare the accuracy of mammography (MG) and magnetic resonance imaging (MRI) in predicting the size of residual tumors.

Methods

The imaging findings and pathological results for 29 patients with residual microcalcifications after NAC were reviewed. We compared the agreement of the measured extent of residual microcalcifications based on MG and residual enhancement based on MRI with the residual tumor size based on pathology.

Results

At final pathology, residual microcalcifications were malignant in 55.2% of cases and benign in 44.8% of cases. In 36% of non-pCR cases, the remaining microcalcifications were benign. Compared with the measurements of residual tumor obtained from pathology, MG showed poor agreement, and MRI showed moderate agreement, for the entire group (concordance correlation coefficient [CCC] = 0.196 vs. 0.566). Regarding the receptor status, the agreement of measurements obtained by MG was superior to that obtained by MRI (CCC = 0.5629, 0.5472 vs. 0.4496, 0.4279) for ER(+) and HER2(−) tumors. In ER(−) tumors, the measurements obtained by MG showed the lowest agreement with the pathological tumor size, which had the highest agreement with those obtained by MRI (CCC = − 0.0162 vs. 0.8584).

Conclusions

Residual mammographic microcalcifications after NAC did not correlate with malignancy in 44.8% of cases. Residual microcalcifications on MG were poorly correlated with pathological tumor size, and MRI might be more reliable for predicting residual tumor size after NAC. Tumor receptor status affected the accuracy of both MG and MRI for predicting residual tumor size after NAC.

Trial registration

CRIS, KCT0002281; registered 6 April 2015, retrospectively registered

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Postoperative survival of EGFR-TKI-targeted therapy in non-small cell lung cancer patients with EGFR 19 or 21 mutations: a retrospective study

Abstract

Background

The aim of this retrospective study is to identify epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer patients and to compare the long-term postoperative outcomes in different EGFR-TKI-targeted therapy effects between the different EGFR mutation groups.

Methods

A total of 2094 postoperative non-small cell lung cancer (NSCLC) patients with EGFR gene detection were collected in the Department of Pathology in the Cancer Hospital Chinese Academy of Medical Sciences from January 2003 to January 2014. Three hundred sixty-three patients were treated with EGFR tyrosine kinase inhibitor (TKI) after surgery: 184 harbored the exon 19 deletion mutation and 179 cases carried the exon 21 L858R point mutation. The end points included progression-free survival (PFS), overall survival (OS), and the response rate.

Results

OS was increased in the EGFR exon 19 deletion group compared with the exon 21 L858R point mutation group (92 vs. 65 months; P < 0.001). But the median PFS did not differ between two groups (12 vs 14 months). The objective response rate (ORR) in 19 deletion group was increased compared with L858R mutation patients (28.35 vs. 22.73%). The disease control rate (DCR) of patients with 19 deletion benefited more from targeted therapy, compared with L858R group (93.71 vs. 84.31%, P = 0.014). In 19 deletion group, a high ORR and DCR were noted in patients treated with icotinib, 16 out of 18 achieved stable disease (SD), and the DCR in this population was 100%.

Conclusions

EGFR subtypes could influence the postoperative survival of NSCLC patients with TKI-targeted therapy.

http://ift.tt/2lYrZo0

Residual microcalcifications after neoadjuvant chemotherapy for locally advanced breast cancer: comparison of the accuracies of mammography and MRI in predicting pathological residual tumor

Abstract

Background

The aims of this study were to correlate residual mammographic microcalcifications after neoadjuvant chemotherapy (NAC) with pathological results and to compare the accuracy of mammography (MG) and magnetic resonance imaging (MRI) in predicting the size of residual tumors.

Methods

The imaging findings and pathological results for 29 patients with residual microcalcifications after NAC were reviewed. We compared the agreement of the measured extent of residual microcalcifications based on MG and residual enhancement based on MRI with the residual tumor size based on pathology.

Results

At final pathology, residual microcalcifications were malignant in 55.2% of cases and benign in 44.8% of cases. In 36% of non-pCR cases, the remaining microcalcifications were benign. Compared with the measurements of residual tumor obtained from pathology, MG showed poor agreement, and MRI showed moderate agreement, for the entire group (concordance correlation coefficient [CCC] = 0.196 vs. 0.566). Regarding the receptor status, the agreement of measurements obtained by MG was superior to that obtained by MRI (CCC = 0.5629, 0.5472 vs. 0.4496, 0.4279) for ER(+) and HER2(−) tumors. In ER(−) tumors, the measurements obtained by MG showed the lowest agreement with the pathological tumor size, which had the highest agreement with those obtained by MRI (CCC = − 0.0162 vs. 0.8584).

Conclusions

Residual mammographic microcalcifications after NAC did not correlate with malignancy in 44.8% of cases. Residual microcalcifications on MG were poorly correlated with pathological tumor size, and MRI might be more reliable for predicting residual tumor size after NAC. Tumor receptor status affected the accuracy of both MG and MRI for predicting residual tumor size after NAC.

Trial registration

CRIS, KCT0002281; registered 6 April 2015, retrospectively registered

http://ift.tt/2yBhT2w

Applying Social Network Analysis to Identify the Social Support Needs of Adolescent and Young Adult Cancer Patients and Survivors

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


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Applying Social Network Analysis to Identify the Social Support Needs of Adolescent and Young Adult Cancer Patients and Survivors

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


http://ift.tt/2yBH05e

Validation and comparison of the molecular classifications of pancreatic carcinomas

Abstract

Four molecular classifications of pancreatic ductal adenocarcinoma (PDAC), biologically and clinically relevant and based on gene expression profiles, were established in the recent years, including the Collisson's, Moffitt's ("tumor" and "stroma" classifications), and Bailey's classifications. The aim of this study was to validate the prognostic value of the Moffitt's classifications and to compare the Collisson's, Moffitt's, and Bailey's classifications in a large series of samples. We collected clinical and gene expression data of PDAC samples from 15 public data sets, resulting in a total of 846 primary cancer samples, including 601 with survival annotation. All samples were classified according to each of the four multigene classifiers. We confirmed the independent prognostic value of the Moffitt "tumor", Moffitt "stroma", and Bailey's classifications, but not that of the Collisson's classification. Despite a relatively low gene overlap, all classifications were associated with pathological grade, an important prognostic feature and reflect of intrinsic molecular characteristics of tumors. The concordance rate in term of "good-prognosis" vs. "poor-prognosis" prediction by classifiers was relatively high (from 73 to 86%) between the three "tumor" classifications based on tumor gene lists (Collisson, Moffitt "tumor", Bailey), but low (from 50 to 60%) with the Moffitt's stroma classification based on stroma genes. Multivariate analysis incorporating the four classifiers together retained as significant variables the Moffitt "stroma" and Bailey classifications, highlighting the complementarity of classifiers based on tumor epithelium (Bailey) and tumor stroma (Moffitt stroma). Our results reinforce the clinical validity of subtyping in PDAC, which should be regarded as a collection of separate diseases. Beside their clinical utility that remains to be demonstrated, the clinical interest of the subtypes, notably those from Bailey's and Moffitt's "stroma" classifiers that show independent prognostic value, will be reinforced by the identification of new biomarkers and/or therapeutic targets in each subtype for designing and testing novel specific targeted therapies.

http://ift.tt/2hgtyw1

Clinical outcomes of graves’ ophthalmopathy treated with intensity modulated radiation therapy

Abstract

Background

Radiation for Graves' ophthalmopathy (GO) has traditionally utilized lateral opposing fields (LOF) or three-dimensional conformal radiotherapy (3DCRT) technique. The current study was conducted to report clinical outcomes and therapeutic effects of intensity modulated radiation therapy (IMRT) in treating GO patients.

Methods

One hundred sixteen patients with GO were treated with IMRT as initial local therapy between July 2010 and August 2013, with a median follow-up of 62 months (range 45–81 months). Radiotherapy dose was 20 Gy in 10 fractions within two to three weeks. The immediate and long-term response to IMRT was evaluated in GO severity score and in each category of symptoms. Acute and long-term complications were recorded to assess its safety.

Results

Symptom severity score significantly fell from the start of treatment to 4- or 6- month post-IMRT (P < 0.01). In total, 85 patients (73.3%) experienced improvement of GO symptoms in the first half-year, and only 4 of them (4.7%) suffered recurrence of the GO symptoms during the subsequent follow-ups. Orbital pain, tearing and extraocular muscle dysfunction had the best treatment reaction to IMRT, while proptosis and blurred vision were the most refractory symptoms. Acute complications were slight and self-limited, mainly including intermittent eye redness in 9 patients (7.8%), sideburns hair loss in 19 patients (16.4%), increased milphosis or madarosis in 23 patients (19.8%) and pseudo-progression of GO symptoms in 15 patients (12.9%). For long-term complications, chronic xerophthalmias occurred in 7 patients (6.03%), cataract developed in 2 patients (1.72%), and all were well-managed by medical interventions. Radiation retinopathy and secondary malignancy was not presented in the cohort.

Conclusion

The study demonstrated that IMRT could serve as a viable option in treating GO patients, with a satisfactory symptom control ability, and relatively slight and acceptable post-radiotherapeutic complications.

http://ift.tt/2zlf9mK

First intraindividual comparison of contrast-enhanced MRI, FET- and DOTATOC- PET in patients with intracranial meningiomas

Abstract

Background

For irradiation treatment planning of meningiomas the use of PET-scans is well established. The most frequently used tracers are either based on amino acids or the somatostatin receptor ligand DOTATOC. Since up to now no inter-institutionally accepted standard PET-tracer has been defined, the aim of this study was to evaluate the influence of these different types of PET-tracers on the GTV-definition.

Methods

Twenty-one patients suffering from intracranial meningiomas underwent CT, MRI, FET- and DOTATOC-PET. First, tumour extension was delineated after image-fusion of CT and MRI (GTV_CT/MRI). Then distinct GTVs based either on FET- or DOTATOC-PET were contoured and compared with each other as well with GTV_CT/MRI.

Results

Every tumour showed typical enhancement of DOTATOC, but two meningiomas remained FET-negative. The mean relative overlap volume of GTV_FET and GTV_DOTATOC was only 41.9% and there was a significantly stronger correlation between GTV_CT/MRI and GTV_DOTATOC than between GTV_CT/MRI and GTV_FET.

Conclusions

Further investigations are necessary to clarify the minor conformity of DOTATOC- and FET-PET in meningiomas. Because of the receptor targeting, DOTATOC is known to be more specific for meningiomas and will remain the standard in our institution with the known limitation in areas nearby the pituitary gland.

http://ift.tt/2y99iiW

Management of organ motion in scanned ion beam therapy

Abstract

Scanned ion beam therapy has special demands for treatment of intra-fractionally moving tumors such as lesions in lung or liver. Interplay effects between beam and organ motion can in those settings lead to under-dosage of the target volume. Dedicated treatment techniques such as gating or abdominal compression are required. In addition 4D treatment planning should be used to determine strategies for patient specific treatment planning such as an increased beam focus or the use of internal target volumes incorporating range changes.

Several work packages of the Clinical Research Units 214 and 214/2 funded by the German Research Council investigated the management of organ motion in scanned ion beam therapy. A focus was laid on 4D treatment planning using TRiP4D and the development of motion mitigation strategies including their quality assurance. This review focuses on the activity in the second funding period covering adaptive treatment planning strategies, 4D treatment plan optimization, and the application of motion management in pre-clinical research on radiation therapy of cardiac arrhythmias.

http://ift.tt/2zlEU6F

Normal lung sparing Tomotherapy technique in stage III lung cancer

Abstract

Purpose

Radiation pneumonitis (RP) has been a challenging obstacle in treating stage III lung cancer patients. Beam angle optimization (BAO) technique for Tomotherapy was developed to reduce the normal lung dose for stage III non-small cell lung cancer (NSCLC). Comparative analyses on plan quality by 3 different Intensity-modulated radiation therapy (IMRT) methods with BAO were done.

Materials and methods

Ten consecutive stage IIIB NSCLC patients receiving linac-based static IMRT (L-IMRT) with total 66 Gy in 33 fractions to the PTV were selected. Two additional Tomotherapy-based IMRT plans (helical beam (TH-IMRT) and static beam (TD-IMRT)) were generated on each patient. To reduce the normal lung dose, Beam angles were optimized by using complete and directional block functions in Tomotherapy based on knowledge based statistical analysis. Plan quality was compared with target coverage, normal organ sparing capability, and normal tissue complication probability (NTCP). Actual beam delivery times and risk of RP related with planning target volume (PTV) were also evaluated.

Results

The best PTV coverage measured by conformity index and homogeneity index was achievable by TH-IMRT (0.82 and 1.06), followed by TD-IMRT (0.81 and 1.07) and L-IMRT (0.75 and 1.08). Mean lung dose was the lowest in TH-IMRT plan followed by TD-IMRT and L-IMRT, all of which were ≤20 Gy. TH-IMRT plan could significantly lower the lung volumes receiving low to medium dose levels: V_5~30 when compared to L-IMRT plan; and V_5~20 when compared to TD-IMRT plan, respectively. TD-IMRT plan was significantly better than L-IMRT with respects to V₂₀ and V₃₀ and there was no significant difference with respect to V₄₀ among three plans. The NTCP of the lung was the lowest in TH-IMRT plan, followed by TD-IMRT and L-IMRT (6.42% vs. 6.53% vs. 8.11%). Beam delivery time was the shortest in TD-IMRT plan followed by L-IMRT. As PTV length increased, NTCP and Mean lung dose proportionally increased significantly in all three plans.

Conclusion

Advantageous profiles by TH-IMRT could be achieved by BAO by complete and directional block functions. Current observation could help radiation oncologists to make wise selection of IMRT method for stage IIIB NSCLC.

http://ift.tt/2y8P9d8

Multicriteria plan optimization in the hands of physicians: a pilot study in prostate cancer and brain tumors

Abstract

Background

The purpose of this study was to demonstrate the feasibility of physician driven planning in intensity modulated radiotherapy (IMRT) with a multicriteria optimization (MCO) treatment planning system and template based plan optimization. Exploiting the full planning potential of MCO navigation, this alternative planning approach intends to improve planning efficiency and individual plan quality.

Methods

Planning was retrospectively performed on 12 brain tumor and 10 post-prostatectomy prostate patients previously treated with MCO-IMRT. For each patient, physicians were provided with a template-based generated Pareto surface of optimal plans to navigate, using the beam angles from the original clinical plans. We compared physician generated plans to clinically delivered plans (created by dosimetrists) in terms of dosimetric differences, physician preferences and planning times.

Results

Plan qualities were similar, however physician generated and clinical plans differed in the prioritization of clinical goals. Physician derived prostate plans showed significantly better sparing of the high dose rectum and bladder regions (p(D1) < 0.05; D1: dose received by 1% of the corresponding structure). Physicians' brain tumor plans indicated higher doses for targets and brainstem (p(D1) < 0.05). Within blinded plan comparisons physicians preferred the clinical plans more often (brain: 6:3 out of 12, prostate: 2:6 out of 10) (not statistically significant). While times of physician involvement were comparable for prostate planning, the new workflow reduced the average involved time for brain cases by 30%. Planner times were reduced for all cases. Subjective benefits, such as a better understanding of planning situations, were observed by clinicians through the insight into plan optimization and experiencing dosimetric trade-offs.

Conclusions

We introduce physician driven planning with MCO for brain and prostate tumors as a feasible planning workflow. The proposed approach standardizes the planning process by utilizing site specific templates and integrates physicians more tightly into treatment planning. Physicians' navigated plan qualities were comparable to the clinical plans. Given the reduction of planning time of the planner and the equal or lower planning time of physicians, this approach has the potential to improve departmental efficiencies.

http://ift.tt/2zlENYN

Validation and comparison of the molecular classifications of pancreatic carcinomas

Abstract

Four molecular classifications of pancreatic ductal adenocarcinoma (PDAC), biologically and clinically relevant and based on gene expression profiles, were established in the recent years, including the Collisson's, Moffitt's ("tumor" and "stroma" classifications), and Bailey's classifications. The aim of this study was to validate the prognostic value of the Moffitt's classifications and to compare the Collisson's, Moffitt's, and Bailey's classifications in a large series of samples. We collected clinical and gene expression data of PDAC samples from 15 public data sets, resulting in a total of 846 primary cancer samples, including 601 with survival annotation. All samples were classified according to each of the four multigene classifiers. We confirmed the independent prognostic value of the Moffitt "tumor", Moffitt "stroma", and Bailey's classifications, but not that of the Collisson's classification. Despite a relatively low gene overlap, all classifications were associated with pathological grade, an important prognostic feature and reflect of intrinsic molecular characteristics of tumors. The concordance rate in term of "good-prognosis" vs. "poor-prognosis" prediction by classifiers was relatively high (from 73 to 86%) between the three "tumor" classifications based on tumor gene lists (Collisson, Moffitt "tumor", Bailey), but low (from 50 to 60%) with the Moffitt's stroma classification based on stroma genes. Multivariate analysis incorporating the four classifiers together retained as significant variables the Moffitt "stroma" and Bailey classifications, highlighting the complementarity of classifiers based on tumor epithelium (Bailey) and tumor stroma (Moffitt stroma). Our results reinforce the clinical validity of subtyping in PDAC, which should be regarded as a collection of separate diseases. Beside their clinical utility that remains to be demonstrated, the clinical interest of the subtypes, notably those from Bailey's and Moffitt's "stroma" classifiers that show independent prognostic value, will be reinforced by the identification of new biomarkers and/or therapeutic targets in each subtype for designing and testing novel specific targeted therapies.

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Clinical outcomes of graves’ ophthalmopathy treated with intensity modulated radiation therapy

Abstract

Background

Radiation for Graves' ophthalmopathy (GO) has traditionally utilized lateral opposing fields (LOF) or three-dimensional conformal radiotherapy (3DCRT) technique. The current study was conducted to report clinical outcomes and therapeutic effects of intensity modulated radiation therapy (IMRT) in treating GO patients.

Methods

One hundred sixteen patients with GO were treated with IMRT as initial local therapy between July 2010 and August 2013, with a median follow-up of 62 months (range 45–81 months). Radiotherapy dose was 20 Gy in 10 fractions within two to three weeks. The immediate and long-term response to IMRT was evaluated in GO severity score and in each category of symptoms. Acute and long-term complications were recorded to assess its safety.

Results

Symptom severity score significantly fell from the start of treatment to 4- or 6- month post-IMRT (P < 0.01). In total, 85 patients (73.3%) experienced improvement of GO symptoms in the first half-year, and only 4 of them (4.7%) suffered recurrence of the GO symptoms during the subsequent follow-ups. Orbital pain, tearing and extraocular muscle dysfunction had the best treatment reaction to IMRT, while proptosis and blurred vision were the most refractory symptoms. Acute complications were slight and self-limited, mainly including intermittent eye redness in 9 patients (7.8%), sideburns hair loss in 19 patients (16.4%), increased milphosis or madarosis in 23 patients (19.8%) and pseudo-progression of GO symptoms in 15 patients (12.9%). For long-term complications, chronic xerophthalmias occurred in 7 patients (6.03%), cataract developed in 2 patients (1.72%), and all were well-managed by medical interventions. Radiation retinopathy and secondary malignancy was not presented in the cohort.

Conclusion

The study demonstrated that IMRT could serve as a viable option in treating GO patients, with a satisfactory symptom control ability, and relatively slight and acceptable post-radiotherapeutic complications.

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via IFTTT

First intraindividual comparison of contrast-enhanced MRI, FET- and DOTATOC- PET in patients with intracranial meningiomas

Abstract

Background

For irradiation treatment planning of meningiomas the use of PET-scans is well established. The most frequently used tracers are either based on amino acids or the somatostatin receptor ligand DOTATOC. Since up to now no inter-institutionally accepted standard PET-tracer has been defined, the aim of this study was to evaluate the influence of these different types of PET-tracers on the GTV-definition.

Methods

Twenty-one patients suffering from intracranial meningiomas underwent CT, MRI, FET- and DOTATOC-PET. First, tumour extension was delineated after image-fusion of CT and MRI (GTV_CT/MRI). Then distinct GTVs based either on FET- or DOTATOC-PET were contoured and compared with each other as well with GTV_CT/MRI.

Results

Every tumour showed typical enhancement of DOTATOC, but two meningiomas remained FET-negative. The mean relative overlap volume of GTV_FET and GTV_DOTATOC was only 41.9% and there was a significantly stronger correlation between GTV_CT/MRI and GTV_DOTATOC than between GTV_CT/MRI and GTV_FET.

Conclusions

Further investigations are necessary to clarify the minor conformity of DOTATOC- and FET-PET in meningiomas. Because of the receptor targeting, DOTATOC is known to be more specific for meningiomas and will remain the standard in our institution with the known limitation in areas nearby the pituitary gland.

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via IFTTT

Management of organ motion in scanned ion beam therapy

Abstract

Scanned ion beam therapy has special demands for treatment of intra-fractionally moving tumors such as lesions in lung or liver. Interplay effects between beam and organ motion can in those settings lead to under-dosage of the target volume. Dedicated treatment techniques such as gating or abdominal compression are required. In addition 4D treatment planning should be used to determine strategies for patient specific treatment planning such as an increased beam focus or the use of internal target volumes incorporating range changes.

Several work packages of the Clinical Research Units 214 and 214/2 funded by the German Research Council investigated the management of organ motion in scanned ion beam therapy. A focus was laid on 4D treatment planning using TRiP4D and the development of motion mitigation strategies including their quality assurance. This review focuses on the activity in the second funding period covering adaptive treatment planning strategies, 4D treatment plan optimization, and the application of motion management in pre-clinical research on radiation therapy of cardiac arrhythmias.

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via IFTTT