Chemotherapy is administered to a minority of hospitalized patients with diffuse large B-cell lymphoma and is associated with less likelihood of death during hospitalization

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Anita J. Kumar, Tobi Henzer, Angie Mae Rodday, Susan K. Parsons
BackgroundWhile treatment of DLBCL is largely outpatient, some patients require planned or unplanned admissions for chemotherapy, new diagnosis, relapse, or toxicity. We examined risk factors for receipt of inpatient chemotherapy and death during hospitalization.MethodsWe analyzed data from the 2012–2013 HCUP-NIS. We identified patient and hospital characteristics that were associated with chemotherapy administration and death.ResultsChemotherapy was given in 3260/11,150 (29.2%) of hospitalizations. Younger age, urban teaching hospitals, fewer chronic conditions, male sex, non-Medicare insurance, and "less likelihood of dying" were associated with chemotherapy. Chemotherapy portended lower odds of death; older age and longer hospitalizations were associated with increased odds of death.ConclusionWe identified socio-demographics and clinical characteristics associated with inpatient chemotherapy in DLBCL patients. Chemotherapy is associated with lower odds of death during hospitalization, suggesting that most chemotherapy is given appropriately to non-critically ill patients. Clinical acuity is a stronger predictor of death than socio-demographics.



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Exploring determinants of care-seeking behaviour of oral cancer patients in India: A qualitative content analysis

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Hemamalini Rath, Swikant Shah, Gaurav Sharma, Ekagrata Mishra
BackgroundA major public health concern in India is the high morbidity and mortality rates of oral cancer because of late diagnosis. Among the several determinants of this late diagnosis, the most important is the healthcare-seeking behaviour of the oral cancer patients. The aim of this study was to explore the care-seeking behaviour and its determinants among oral cancer patients.MethodsA face-to-face in-depth interview was conducted among 70 oral cancer patients using a semi-structured questionnaire, and qualitative content analysis of the results was performed.ResultsAll the patients had squamous-cell carcinoma and none had attended any screening programme. The most common site affected was the buccal mucosa with a non-healing wound. Most of the patients contacted a doctor available nearby; only 7% of patients consulted a dentist. Only one patient approached a traditional healer. The median patient delay was 30 (4–365) days and the professional delay was 40 (4–650) days. Enablers included determinants such as increasing symptoms (80%), influence of the society (74%), fear (10%), and social media (3%). The main barriers were lack of awareness (97%), hope that the lesion will heal spontaneously (90%), lack of perception of seriousness (64%), financial constraints (55%), provider switching (47%), and missed diagnosis (44%).ConclusionThe care-seeking path among oral cancer patients is complex, customised, and influenced by multiple patient-related and system-related factors.



http://ift.tt/2CbtuC3

Chemotherapy is administered to a minority of hospitalized patients with diffuse large B-cell lymphoma and is associated with less likelihood of death during hospitalization

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Anita J. Kumar, Tobi Henzer, Angie Mae Rodday, Susan K. Parsons
BackgroundWhile treatment of DLBCL is largely outpatient, some patients require planned or unplanned admissions for chemotherapy, new diagnosis, relapse, or toxicity. We examined risk factors for receipt of inpatient chemotherapy and death during hospitalization.MethodsWe analyzed data from the 2012–2013 HCUP-NIS. We identified patient and hospital characteristics that were associated with chemotherapy administration and death.ResultsChemotherapy was given in 3260/11,150 (29.2%) of hospitalizations. Younger age, urban teaching hospitals, fewer chronic conditions, male sex, non-Medicare insurance, and "less likelihood of dying" were associated with chemotherapy. Chemotherapy portended lower odds of death; older age and longer hospitalizations were associated with increased odds of death.ConclusionWe identified socio-demographics and clinical characteristics associated with inpatient chemotherapy in DLBCL patients. Chemotherapy is associated with lower odds of death during hospitalization, suggesting that most chemotherapy is given appropriately to non-critically ill patients. Clinical acuity is a stronger predictor of death than socio-demographics.



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Exploring determinants of care-seeking behaviour of oral cancer patients in India: A qualitative content analysis

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Hemamalini Rath, Swikant Shah, Gaurav Sharma, Ekagrata Mishra
BackgroundA major public health concern in India is the high morbidity and mortality rates of oral cancer because of late diagnosis. Among the several determinants of this late diagnosis, the most important is the healthcare-seeking behaviour of the oral cancer patients. The aim of this study was to explore the care-seeking behaviour and its determinants among oral cancer patients.MethodsA face-to-face in-depth interview was conducted among 70 oral cancer patients using a semi-structured questionnaire, and qualitative content analysis of the results was performed.ResultsAll the patients had squamous-cell carcinoma and none had attended any screening programme. The most common site affected was the buccal mucosa with a non-healing wound. Most of the patients contacted a doctor available nearby; only 7% of patients consulted a dentist. Only one patient approached a traditional healer. The median patient delay was 30 (4–365) days and the professional delay was 40 (4–650) days. Enablers included determinants such as increasing symptoms (80%), influence of the society (74%), fear (10%), and social media (3%). The main barriers were lack of awareness (97%), hope that the lesion will heal spontaneously (90%), lack of perception of seriousness (64%), financial constraints (55%), provider switching (47%), and missed diagnosis (44%).ConclusionThe care-seeking path among oral cancer patients is complex, customised, and influenced by multiple patient-related and system-related factors.



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Closed-Eye Visualizations in the Setting of Hyponatremia

Purpose. To report a case of closed-eye visualizations and to clarify the different types of hallucinations and their etiologies. Methods. Retrospective case report of a patient with closed-eye visualizations secondary to hyponatremia. Clinical findings, physical exam, laboratory assessment, treatment, and disease course from the patient's hospitalization were used in creating this report. Follow-up data after discharge were also obtained. Results. Closed-eye visualizations were diagnosed as secondary to hyponatremia, as they did not occur with the eyes open, and potential alternate causes were excluded. Serum sodium nadir was 119 mEq/L. Symptoms resolved with correction of hyponatremia via fluid resuscitation and electrolyte replenishment. There has been no recurrence of the symptoms. Conclusion. This patient had hallucinations exclusively with the eyes closed, which must be differentiated from the release hallucinations seen with the eyes open in Charles Bonnet syndrome. This patient had no visual loss or retinal disease, which should be suspected in open eye hallucinations.

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CyberKnife robotic radiosurgery in the multimodal management of acromegaly patients with invasive macroadenoma: a single center’s experience

Abstract

Surgery is the primary treatment for acromegaly. However, surgery may not be curative of some tumors, particularly invasive macroadenomas. Adjuvant radiation, specifically robotic stereotactic radiosurgery (rSRS), may improve the endocrine outcome. We retrospectively reviewed hormonal and radiological data of 22 acromegalic patients with invasive macroadenomas treated with rSRS at Stanford University Medical Center between 2000 and 2016. Prior to treatment, the tumor's median maximal diameter was 19 mm (2.5–50 mm). Cavernous sinus invasion occurred in 19 patients (86.3%) and compression of the optic chiasm in 2 (9.0%). At last follow up, with an average follow up of 43.2 months, all patients had a reduction in their IGF-1 levels (median IGF-1% upper limit of normal (ULN) baseline: 136% vs last follow up: 97%; p = 0.05); 9 patients (40.9%) were cured, and 4 (18.1%) others demonstrated biochemical control of acromegaly. The median time to cure was 50 months and the mean interval to cure or biochemical control was 30.3 months (± 24 months, range 6–84 months). Hypopituitarism was present in 8 patients (36.3%) and new pituitary deficits occurred in 6 patients with a median latency of 31.6 ± 14.5 months. At final radiologic follow-up, 3 tumors (13.6%) were smaller and 19 were stable in size. The mean biologically effective dose (BED) was higher in subjects cured compared to those with persistent disease, 163 Gy3 (± 47) versus 111 Gy3 (± 43), respectively (p = 0.01). No patient suffered visual deterioration. Robotic SRS is a safe and effective treatment for acromegaly: radiation-induced visual complications and hypopituitarism is rare.

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CyberKnife robotic radiosurgery in the multimodal management of acromegaly patients with invasive macroadenoma: a single center’s experience

Abstract

Surgery is the primary treatment for acromegaly. However, surgery may not be curative of some tumors, particularly invasive macroadenomas. Adjuvant radiation, specifically robotic stereotactic radiosurgery (rSRS), may improve the endocrine outcome. We retrospectively reviewed hormonal and radiological data of 22 acromegalic patients with invasive macroadenomas treated with rSRS at Stanford University Medical Center between 2000 and 2016. Prior to treatment, the tumor's median maximal diameter was 19 mm (2.5–50 mm). Cavernous sinus invasion occurred in 19 patients (86.3%) and compression of the optic chiasm in 2 (9.0%). At last follow up, with an average follow up of 43.2 months, all patients had a reduction in their IGF-1 levels (median IGF-1% upper limit of normal (ULN) baseline: 136% vs last follow up: 97%; p = 0.05); 9 patients (40.9%) were cured, and 4 (18.1%) others demonstrated biochemical control of acromegaly. The median time to cure was 50 months and the mean interval to cure or biochemical control was 30.3 months (± 24 months, range 6–84 months). Hypopituitarism was present in 8 patients (36.3%) and new pituitary deficits occurred in 6 patients with a median latency of 31.6 ± 14.5 months. At final radiologic follow-up, 3 tumors (13.6%) were smaller and 19 were stable in size. The mean biologically effective dose (BED) was higher in subjects cured compared to those with persistent disease, 163 Gy3 (± 47) versus 111 Gy3 (± 43), respectively (p = 0.01). No patient suffered visual deterioration. Robotic SRS is a safe and effective treatment for acromegaly: radiation-induced visual complications and hypopituitarism is rare.

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NUP98-BPTF gene fusion identified in primary refractory acute megakaryoblastic leukemia of infancy

Abstract

The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners. We report a novel NUP98-BPTF fusion in an infant presenting with primary refractory AMKL. In this NUP98r, the C-terminal chromatin recognition modules of BPTF, a core subunit of the NURF (Nucleosome Remodeling Factor) ATP-dependent chromatin-remodeling complex, are fused to the N-terminal moiety of NUP98, creating and in frame NUP98-BPTF fusion, with structural homology to NUP98-KDM5A. The leukemic blasts expressed two NUP98-BPTF splicing variants, containing one or two tandemly spaced PHD chromatin reader domains. Our study also identified an unreported wild type BPTF splicing variant encoding for 2 PHD domains, detected both in normal cord blood CD34⁺ cells and in leukemic blasts, as with the fly BPTF homolog, Nurf301. Disease course was marked by rapid progression and primary chemoresistance, with ultimately significant tumor burden reduction following treatment with a clofarabine containing regimen. In sum, we report 2 novel NUP98-BPTF fusion isoforms that contribute to refine the NUP98r subgroup of pediatric AMKL. Multicenter clinical trials are critically required to determine the frequency of this fusion in AMKL patients and explore innovative treatment strategies for a disease still plagued with poor outcomes. This article is protected by copyright. All rights reserved.

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NUP98-BPTF gene fusion identified in primary refractory acute megakaryoblastic leukemia of infancy

Abstract

The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners. We report a novel NUP98-BPTF fusion in an infant presenting with primary refractory AMKL. In this NUP98r, the C-terminal chromatin recognition modules of BPTF, a core subunit of the NURF (Nucleosome Remodeling Factor) ATP-dependent chromatin-remodeling complex, are fused to the N-terminal moiety of NUP98, creating and in frame NUP98-BPTF fusion, with structural homology to NUP98-KDM5A. The leukemic blasts expressed two NUP98-BPTF splicing variants, containing one or two tandemly spaced PHD chromatin reader domains. Our study also identified an unreported wild type BPTF splicing variant encoding for 2 PHD domains, detected both in normal cord blood CD34⁺ cells and in leukemic blasts, as with the fly BPTF homolog, Nurf301. Disease course was marked by rapid progression and primary chemoresistance, with ultimately significant tumor burden reduction following treatment with a clofarabine containing regimen. In sum, we report 2 novel NUP98-BPTF fusion isoforms that contribute to refine the NUP98r subgroup of pediatric AMKL. Multicenter clinical trials are critically required to determine the frequency of this fusion in AMKL patients and explore innovative treatment strategies for a disease still plagued with poor outcomes. This article is protected by copyright. All rights reserved.

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FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells

Abstract

F-box and WD repeat domain-containing 7(FBW7) is a SCF-type E3 ubiquitin ligase targeting a multitude of oncoproteins for degradation. Acting as one of the most important tumor suppressor it is frequently inactivated in various tumors. In this study we aimed to evaluate the relationship of FBW7 with glioma pathology and prognosis, and examine its effect in glioma malignancies and temozolomide(TMZ)-based therapy. Clinical tissues and TCGA database analysis revealed FBW7 expression was correlated inversely with glioma histology and positively with patient survival time. Lentivirus transfection- induced FBW7 overexpression significantly suppressed proliferation, invasion and migration of U251 and U373 cells whereas knockdown of FBW7 by targeted shRNA promoted proliferation, invasion and migration of glioma cells. Most importantly, the expression level of FBW7 was found to affect 50% inhibition concentration(IC50) of U251 and the TMZ resistant variant. Combining TMZ with FBW7 overexpression notably increased the cytotoxicity than TMZ treatment alone, which was conversely attenuated by FBW7 knockdown. Moreover, flow cytometry(FC) analysis showed either overexpression of FBW7, TMZ or the combination increased proportion of G2/M arrest and apoptotic rate whereas FBW7 inhibition reduced G2/M arrest and apoptosis in U251 cells. Finally, mechanistic study found FBW7 overexpression downregulated Aurora B, Mcl1 and Notch1 levels in a time-dependent pattern and this expressional suppression was independent of TMZ. These findings collectively demonstrate the critical role of FBW7 as a prognostic factor and a potential target to overcome chemoresistance of glioblastoma.

This article is protected by copyright. All rights reserved.

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FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells

Abstract

F-box and WD repeat domain-containing 7(FBW7) is a SCF-type E3 ubiquitin ligase targeting a multitude of oncoproteins for degradation. Acting as one of the most important tumor suppressor it is frequently inactivated in various tumors. In this study we aimed to evaluate the relationship of FBW7 with glioma pathology and prognosis, and examine its effect in glioma malignancies and temozolomide(TMZ)-based therapy. Clinical tissues and TCGA database analysis revealed FBW7 expression was correlated inversely with glioma histology and positively with patient survival time. Lentivirus transfection- induced FBW7 overexpression significantly suppressed proliferation, invasion and migration of U251 and U373 cells whereas knockdown of FBW7 by targeted shRNA promoted proliferation, invasion and migration of glioma cells. Most importantly, the expression level of FBW7 was found to affect 50% inhibition concentration(IC50) of U251 and the TMZ resistant variant. Combining TMZ with FBW7 overexpression notably increased the cytotoxicity than TMZ treatment alone, which was conversely attenuated by FBW7 knockdown. Moreover, flow cytometry(FC) analysis showed either overexpression of FBW7, TMZ or the combination increased proportion of G2/M arrest and apoptotic rate whereas FBW7 inhibition reduced G2/M arrest and apoptosis in U251 cells. Finally, mechanistic study found FBW7 overexpression downregulated Aurora B, Mcl1 and Notch1 levels in a time-dependent pattern and this expressional suppression was independent of TMZ. These findings collectively demonstrate the critical role of FBW7 as a prognostic factor and a potential target to overcome chemoresistance of glioblastoma.

This article is protected by copyright. All rights reserved.

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Cervico-shoulder dystonia following lateral medullary infarction: a case report and review of the literature

Secondary cervical dystonia is induced by organic brain lesions involving the basal ganglia, thalamus, cerebellum, and brain stem. It is extremely rare to see cervical dystonia induced by a medullary lesion.

http://ift.tt/2soQYnP

Brain metastasis in gastroesophageal adenocarcinoma and HER2 status

Abstract

The increased survival of patients with gastroesophageal adenocarcinoma (GAD) following improvements in treatment has been accompanied by a rising incidence of secondary brain metastasis. HER2 amplification/overexpression, which has been associated with an increased risk of brain metastasis in breast cancer, is found in about 20% of patients with GAD. The aim of this study was to evaluate the effect of HER2 status on brain metastasis in GAD. The database of a tertiary cancer center was searched for patients with GAD diagnosed in 2011–2015, and data were collected on clinical characteristics, brain metastasis, HER2 status, and outcome. We identified 404 patients with a confirmed diagnosis of GAD. HER2 results were available for 298: 69 (23.2%) positive and 227 negative. Brain metastasis developed in 15 patients with GAD (3.7%); HER2 results, available in 13, were positive in 6, negative in 6, and equivocal in 1. The brain metastasis rate was significantly higher in HER2-positive than HER2-negative patients with GAD (6/69, 8.7% vs. 6/227, 2.6%; RR = 3.3, 95% CI 1.1–9.9, p = 0.034). Median overall survival from diagnosis of brain metastasis was 2.3 months, with no significant difference by HER2 status. HER2 positive GAD patients may be at increased risk to develop BM. Clinicians should maintain a lower threshold for performing brain imaging in patients with HER2-positive GAD given their increased risk of brain metastasis. The role of anti-HER2 agents in the development and treatment of brain metastasis in GAD warrants further study.

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Impact of an Interprofessional Primary Care Training on Fear of Cancer Recurrence on Clinicians’ Knowledge, Self-Efficacy, Anticipated Practice Behaviors, and Attitudes Toward Survivorship Care

Abstract

There are an estimated 15.5 million cancer survivors in the United States, with numbers projected to increase. Many cancer survivors are receiving survivorship care in primary care settings, yet primary care providers report a need for additional training on addressing medical and psychosocial concerns of cancer survivors. This paper presents findings from a pilot study on the effectiveness of a novel training for interprofessional primary care providers on the clinically significant issue of fear of cancer recurrence. The on-site training was provided to a total of 46 participants, including physicians (61%), physician assistants (11%), nurse practitioners (7%), nurses (17%), and social workers (4%) in six different primary care practices. The average number of years of professional experience was 18.8, with standard deviation of 10.9. Results of paired-sample t tests indicated that the training increased knowledge and self-efficacy of providers in identifying and addressing FCR. The training was well-received by participants, who had high confidence in implementing practice behavior changes, although they also identified barriers. Results suggest the feasibility of a brief training for continuing education and have implications for models of care delivery in cancer survivorship.

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Brain metastasis in gastroesophageal adenocarcinoma and HER2 status

Abstract

The increased survival of patients with gastroesophageal adenocarcinoma (GAD) following improvements in treatment has been accompanied by a rising incidence of secondary brain metastasis. HER2 amplification/overexpression, which has been associated with an increased risk of brain metastasis in breast cancer, is found in about 20% of patients with GAD. The aim of this study was to evaluate the effect of HER2 status on brain metastasis in GAD. The database of a tertiary cancer center was searched for patients with GAD diagnosed in 2011–2015, and data were collected on clinical characteristics, brain metastasis, HER2 status, and outcome. We identified 404 patients with a confirmed diagnosis of GAD. HER2 results were available for 298: 69 (23.2%) positive and 227 negative. Brain metastasis developed in 15 patients with GAD (3.7%); HER2 results, available in 13, were positive in 6, negative in 6, and equivocal in 1. The brain metastasis rate was significantly higher in HER2-positive than HER2-negative patients with GAD (6/69, 8.7% vs. 6/227, 2.6%; RR = 3.3, 95% CI 1.1–9.9, p = 0.034). Median overall survival from diagnosis of brain metastasis was 2.3 months, with no significant difference by HER2 status. HER2 positive GAD patients may be at increased risk to develop BM. Clinicians should maintain a lower threshold for performing brain imaging in patients with HER2-positive GAD given their increased risk of brain metastasis. The role of anti-HER2 agents in the development and treatment of brain metastasis in GAD warrants further study.

http://ift.tt/2smCbd7

Impact of an Interprofessional Primary Care Training on Fear of Cancer Recurrence on Clinicians’ Knowledge, Self-Efficacy, Anticipated Practice Behaviors, and Attitudes Toward Survivorship Care

Abstract

There are an estimated 15.5 million cancer survivors in the United States, with numbers projected to increase. Many cancer survivors are receiving survivorship care in primary care settings, yet primary care providers report a need for additional training on addressing medical and psychosocial concerns of cancer survivors. This paper presents findings from a pilot study on the effectiveness of a novel training for interprofessional primary care providers on the clinically significant issue of fear of cancer recurrence. The on-site training was provided to a total of 46 participants, including physicians (61%), physician assistants (11%), nurse practitioners (7%), nurses (17%), and social workers (4%) in six different primary care practices. The average number of years of professional experience was 18.8, with standard deviation of 10.9. Results of paired-sample t tests indicated that the training increased knowledge and self-efficacy of providers in identifying and addressing FCR. The training was well-received by participants, who had high confidence in implementing practice behavior changes, although they also identified barriers. Results suggest the feasibility of a brief training for continuing education and have implications for models of care delivery in cancer survivorship.

http://ift.tt/2EiKRTC

[Why proton therapy? And how?]

[Why proton therapy? And how?]

Bull Cancer. 2018 Feb 05;:

Authors: Thariat J, Habrand JL, Lesueur P, Chaikh A, Kammerer E, Lecomte D, Batalla A, Balosso J, Tessonnier T

Abstract
Proton therapy is a radiotherapy, based on the use of protons, charged subatomic particles that stop at a given depth depending on their initial energy (pristine Bragg peak), avoiding any output beam, unlike the photons used in most of the other modalities of radiotherapy. Proton therapy has been used for 60 years, but has only become ubiquitous in the last decade because of recent major advances in particle accelerator technology. This article reviews the history of clinical implementation of protons, the nature of the technological advances that now allows its expansion at a lower cost. It also addresses the technical and physical specificities of proton therapy and the clinical situations for which proton therapy may be relevant but requires evidence. Different proton therapy techniques are possible. These are explained in terms of their clinical potential by explaining the current terminology (such as cyclotrons, synchrotrons or synchrocyclotrons, using superconducting magnets, fixed line or arm rotary with passive diffusion delivery or active by scanning) in basic words. The requirements associated with proton therapy are increased due to the precision of the depth dose deposit. The learning curve of proton therapy requires that clinical indications be prioritized according to their associated uncertainties (such as range uncertainties and movement in lung tumors). Many clinical indications potentially fall under proton therapy ultimately. Clinical strategies are explained in a paralleled manuscript.

PMID: 29422248 [PubMed - as supplied by publisher]

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[The place of cancer's cure in the personalized medicine and immunotherapy].

[The place of cancer's cure in the personalized medicine and immunotherapy].

Bull Cancer. 2018 Feb 05;:

Authors: Torregrosa C, Rodrigues M, Mamzer-Bruneel MF

PMID: 29422247 [PubMed - as supplied by publisher]

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Efficacy of neurokinin-1 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based chemotherapy: A systematic review and meta-analysis

Publication date: April 2018
Source:Critical Reviews in Oncology/Hematology, Volume 124
Author(s): Massimo Di Maio, Chiara Baratelli, Paolo Bironzo, Francesca Vignani, Emilio Bria, Elisa Sperti, Maddalena Marcato, Fausto Roila
According to current ESMO – MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus. We performed a meta-analysis of randomized trials (RCTs) comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. Primary outcome was complete response (CR), defined as no emesis and no use of rescue medication. 9 trials were eligible, and data of CR were available from 8 trials (1598 patients). Addition of NK1RA improves CR in all phases: acute phase, 94.5% vs. 90.1%; delayed phase, 76.4% vs. 61.7%; overall period, 75.3% vs. 60.4%. There was no significant heterogeneity among trials. In patients receiving carboplatin-based chemotherapy, the addition of NK1RA to dexamethasone and 5-HT3RA is associated with a statistically significant and clinically relevant improvement in CR.



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Efficacy of neurokinin-1 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based chemotherapy: A systematic review and meta-analysis

Publication date: April 2018
Source:Critical Reviews in Oncology/Hematology, Volume 124
Author(s): Massimo Di Maio, Chiara Baratelli, Paolo Bironzo, Francesca Vignani, Emilio Bria, Elisa Sperti, Maddalena Marcato, Fausto Roila
According to current ESMO – MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus. We performed a meta-analysis of randomized trials (RCTs) comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. Primary outcome was complete response (CR), defined as no emesis and no use of rescue medication. 9 trials were eligible, and data of CR were available from 8 trials (1598 patients). Addition of NK1RA improves CR in all phases: acute phase, 94.5% vs. 90.1%; delayed phase, 76.4% vs. 61.7%; overall period, 75.3% vs. 60.4%. There was no significant heterogeneity among trials. In patients receiving carboplatin-based chemotherapy, the addition of NK1RA to dexamethasone and 5-HT3RA is associated with a statistically significant and clinically relevant improvement in CR.



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MOBCdb: a comprehensive database integrating multi-omics data on breast cancer for precision medicine

Abstract

Background

Breast cancer is one of the most frequently diagnosed cancers among women worldwide, characterized by diverse biological heterogeneity. It is well known that complex and combined gene regulation of multi-omics is involved in the occurrence and development of breast cancer.

Results

In this paper, we present the Multi-Omics Breast Cancer Database (MOBCdb), a simple and easily accessible repository that integrates genomic, transcriptomic, epigenomic, clinical, and drug response data of different subtypes of breast cancer. MOBCdb allows users to retrieve simple nucleotide variation (SNV), gene expression, microRNA expression, DNA methylation, and specific drug response data by various search fashions. The genome-wide browser /navigation facility in MOBCdb provides an interface for visualizing multi-omics data of multi-samples simultaneously. Furthermore, the survival module provides survival analysis for all or some of the samples by using data of three omics. The approved public drugs with genetic variations on breast cancer are also included in MOBCdb.

Conclusion

In summary, MOBCdb provides users a unique web interface to the integrated multi-omics data of different subtypes of breast cancer, which enables the users to identify potential novel biomarkers for precision medicine.

http://ift.tt/2BQGotE

Immunosuppressive monocytes (CD14 + /HLA-DR low/− ) increase in childhood precursor B-cell acute lymphoblastic leukemia after induction chemotherapy

Abstract

In tumor microenvironment, immunosuppression is a common event and results from the inhibition of activated immune cells and generation of cells with immunosuppressive capacity, as some subtypes of monocytes. The aim of this study was to evaluate the presence of immunosuppressive CD14⁺/HLA-DR^low/− monocytes in pediatric patients with the diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) and, moreover, verify whether the chemotherapeutic treatment has any effect on these cells. Peripheral blood (PB) and bone marrow (BM) samples were collected from 15 untreated pediatric patients. The presence of CD14⁺/HLA-DR^low/− monocytes was evaluated at diagnosis and in the end of induction chemotherapy by flow cytometry. CD14⁺/HLA-DR^low/− monocytes increase was observed in 60% (9/15) of the patients at the end of the induction therapy. We were able to detect an increase in CD14⁺/HLA-DR^low/− monocytes values in BM and PB samples of pediatric patients with B-ALL. This increase was observed in the end of induction chemotherapy, which leads us to believe that these changes probably could have been induced by the inflammatory process engendered by the cytotoxic treatment or by drugs used in the chemotherapy treatment. This finding may be useful to guide new therapeutic approaches contemplating immunomodulatory drugs that act in the depletion of immunosuppressive monocytes.

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Immunosuppressive monocytes (CD14 + /HLA-DR low/− ) increase in childhood precursor B-cell acute lymphoblastic leukemia after induction chemotherapy

Abstract

In tumor microenvironment, immunosuppression is a common event and results from the inhibition of activated immune cells and generation of cells with immunosuppressive capacity, as some subtypes of monocytes. The aim of this study was to evaluate the presence of immunosuppressive CD14⁺/HLA-DR^low/− monocytes in pediatric patients with the diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) and, moreover, verify whether the chemotherapeutic treatment has any effect on these cells. Peripheral blood (PB) and bone marrow (BM) samples were collected from 15 untreated pediatric patients. The presence of CD14⁺/HLA-DR^low/− monocytes was evaluated at diagnosis and in the end of induction chemotherapy by flow cytometry. CD14⁺/HLA-DR^low/− monocytes increase was observed in 60% (9/15) of the patients at the end of the induction therapy. We were able to detect an increase in CD14⁺/HLA-DR^low/− monocytes values in BM and PB samples of pediatric patients with B-ALL. This increase was observed in the end of induction chemotherapy, which leads us to believe that these changes probably could have been induced by the inflammatory process engendered by the cytotoxic treatment or by drugs used in the chemotherapy treatment. This finding may be useful to guide new therapeutic approaches contemplating immunomodulatory drugs that act in the depletion of immunosuppressive monocytes.

http://ift.tt/2EwjnNj

Expression of Nemo-like kinase in cervical squamous cell carcinoma: a clinicopathological study

http://ift.tt/2H6acSw

Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial

Abstract

Purpose

Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening.

Methods

Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting women 50–69 years biennially, comparing full-field digital mammography (FFDM) plus DBT with FFDM alone. Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds.

Results

24,301 consenting women underwent FFDM + DBT screening over a 2-year period. Results were compared with 59,877 FFDM examinations during prior rounds. Addition of DBT resulted in a non-significant increase in sensitivity (76.2%, 378/496, vs. 80.8%, 227/281, p = 0.151) and a significant increase in specificity (96.4%, 57229/59381 vs. 97.5%, 23427/24020, p < .001). Number of recalls per screen-detected cancer decreased from 6.7 (2530/378) to 3.6 (820/227) with DBT (p < .001). Cancer detection per 1000 women screened increased (6.3, 378/59877, vs. 9.3, 227/24301, p < .001). Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds (2.1, 51/24301 vs. 2.0, 118/59877, p = 0.734). Interval cancers post-DBT were comparable to prior rounds but significantly different in size, grade, and node status from cancers detected only using DBT. 39.6% (19/48) of interval cancers had positive nodes compared with only 3.9% (2/51) of additional DBT-only-detected cancers.

Conclusions

DBT-supplemented screening resulted in significant increases in screen-detected cancers and specificity. However, no significant change was observed in the rate, size, node status, or grade of interval cancers.

ClinicalTrials.gov: NCT01248546.

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Multiple roles of SIM2 in esophageal squamous cell carcinoma and its clinical implications

Summary

The degree of histological differentiation is an important characteristic of cancers and may be associated with their malignant potentials. However, in squamous cell carcinomas, a key transcriptional factor to regulate tumor differentiation is largely unknown. Chemoradiotherapy (CRT) is a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC); however, the survival rate is still below 40%. From microarray data, SIM2 was overexpressed in the epithelial subtype. Here, we investigated the correlation between SIM2 expression and its clinical implication and in vitro and in vivo functions of SIM2 in tumor differentiation and in CRT sensitivity. Although SIM2 was suppressed in cancerous tissues, SIM2-high ESCCs showed a favorable prognosis in CRT. Transient SIM2 expression followed by 3D culture induced expression of differentiation markers and suppressed EMT- and basal cell-markers. The levels of the PDPN-high tumor basal cells and of expression of genes for DNA repair and antioxidant enzymes were reduced in the stable transfectants, and they exhibited high CDDP- and H₂O₂-sensitivities, and their xenografts showed a well-differentiated histology. Reduction of the tumor basal cells was restored by knockdown of ARNT that interacted with SIM2. Together, SIM2 increases CRT sensitivity through the tumor differentiation by cooperation with ARNT.

This article is protected by copyright. All rights reserved.

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Crosstalk of DNA double-strand break repair pathways in PARP inhibitor treatment of BRCA1/2-mutated Cancer

Summary

Germ-line mutations in breast cancer susceptibility gene 1 or 2 (BRCA1 or BRCA2) significantly increase cancer risk in hereditary breast and ovarian cancer syndrome (HBOC). Both genes function in the homologous recombination (HR) pathway of DNA double-strand break (DSB) repair process. Therefore, the DNA-repair defect characteristic in cancer cells brings therapeutic advantage for Poly(ADP-ribose) polymerase (PARP) inhibitor-induced synthetic lethality. The PARP inhibitor-based therapeutics initially causes cancer lethality but acquired resistance mechanisms have been found and need to be elucidated. In particular, it is essential to understand the mechanism of DNA damage and repair to PARP inhibitor treatment in detail. Further investigations have shown the roles of BRCA1/2 and its associations to other molecules in the DSB repair system. Notably, the repair pathway chosen in BRCA1-deficient cells could be entirely different from that in BRCA2-deficient cells after PARP inhibitor treatment. This review describes synthetic lethality and acquired resistance mechanisms to PARP inhibitor via the DSB repair pathway and subsequent repair process. In addition, recent knowledge of resistance mechanisms is discussed. Our model should contribute to the development of novel therapeutic strategies.

This article is protected by copyright. All rights reserved.

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The stearate-to-palmitate ratio modulates endoplasmic reticulum stress and cell apoptosis in non-B non-C hepatoma cells

Summary

The increased prevalence of hepatocellular carcinoma (HCC) without viral infection, namely, NHCC, is a major public health issue worldwide. NHCC is frequently derived from non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), which exhibit dysregulated fatty acid (FA) metabolism. This raises a possibility that NHCC evolves intracellular machineries to adapt to dysregulated FA metabolism. We herein aim to identify NHCC-specifically altered FA and key molecules to achieve the adaptation. In order to analyze FA, imaging mass spectrometry (IMS) was performed on fifteen HCC specimens. The composition of saturated FA (SFA) in NHCC was altered from that in typical HCC. The stearate-to-palmitate ratio (SPR) was significantly increased in NHCC. Associated with the SPR increase, ELOVL6 protein level was up-regulated in NHCC. The knockdown of ELOVL6 reduced SPR, and enhanced endoplasmic reticulum stress, inducing apoptosis of Huh7 and HepG2 cells. In conclusion, NHCC appears to adapt to a FA-rich environment by modulating SPR via ELOVL6.

This article is protected by copyright. All rights reserved.

http://ift.tt/2EViQ5w

Multiple roles of SIM2 in esophageal squamous cell carcinoma and its clinical implications

Summary

The degree of histological differentiation is an important characteristic of cancers and may be associated with their malignant potentials. However, in squamous cell carcinomas, a key transcriptional factor to regulate tumor differentiation is largely unknown. Chemoradiotherapy (CRT) is a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC); however, the survival rate is still below 40%. From microarray data, SIM2 was overexpressed in the epithelial subtype. Here, we investigated the correlation between SIM2 expression and its clinical implication and in vitro and in vivo functions of SIM2 in tumor differentiation and in CRT sensitivity. Although SIM2 was suppressed in cancerous tissues, SIM2-high ESCCs showed a favorable prognosis in CRT. Transient SIM2 expression followed by 3D culture induced expression of differentiation markers and suppressed EMT- and basal cell-markers. The levels of the PDPN-high tumor basal cells and of expression of genes for DNA repair and antioxidant enzymes were reduced in the stable transfectants, and they exhibited high CDDP- and H₂O₂-sensitivities, and their xenografts showed a well-differentiated histology. Reduction of the tumor basal cells was restored by knockdown of ARNT that interacted with SIM2. Together, SIM2 increases CRT sensitivity through the tumor differentiation by cooperation with ARNT.

This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2ESwWEE
via IFTTT

Crosstalk of DNA double-strand break repair pathways in PARP inhibitor treatment of BRCA1/2-mutated Cancer

Summary

Germ-line mutations in breast cancer susceptibility gene 1 or 2 (BRCA1 or BRCA2) significantly increase cancer risk in hereditary breast and ovarian cancer syndrome (HBOC). Both genes function in the homologous recombination (HR) pathway of DNA double-strand break (DSB) repair process. Therefore, the DNA-repair defect characteristic in cancer cells brings therapeutic advantage for Poly(ADP-ribose) polymerase (PARP) inhibitor-induced synthetic lethality. The PARP inhibitor-based therapeutics initially causes cancer lethality but acquired resistance mechanisms have been found and need to be elucidated. In particular, it is essential to understand the mechanism of DNA damage and repair to PARP inhibitor treatment in detail. Further investigations have shown the roles of BRCA1/2 and its associations to other molecules in the DSB repair system. Notably, the repair pathway chosen in BRCA1-deficient cells could be entirely different from that in BRCA2-deficient cells after PARP inhibitor treatment. This review describes synthetic lethality and acquired resistance mechanisms to PARP inhibitor via the DSB repair pathway and subsequent repair process. In addition, recent knowledge of resistance mechanisms is discussed. Our model should contribute to the development of novel therapeutic strategies.

This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2Ehzzij
via IFTTT

The stearate-to-palmitate ratio modulates endoplasmic reticulum stress and cell apoptosis in non-B non-C hepatoma cells

Summary

The increased prevalence of hepatocellular carcinoma (HCC) without viral infection, namely, NHCC, is a major public health issue worldwide. NHCC is frequently derived from non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), which exhibit dysregulated fatty acid (FA) metabolism. This raises a possibility that NHCC evolves intracellular machineries to adapt to dysregulated FA metabolism. We herein aim to identify NHCC-specifically altered FA and key molecules to achieve the adaptation. In order to analyze FA, imaging mass spectrometry (IMS) was performed on fifteen HCC specimens. The composition of saturated FA (SFA) in NHCC was altered from that in typical HCC. The stearate-to-palmitate ratio (SPR) was significantly increased in NHCC. Associated with the SPR increase, ELOVL6 protein level was up-regulated in NHCC. The knockdown of ELOVL6 reduced SPR, and enhanced endoplasmic reticulum stress, inducing apoptosis of Huh7 and HepG2 cells. In conclusion, NHCC appears to adapt to a FA-rich environment by modulating SPR via ELOVL6.

This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2EViQ5w
via IFTTT