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Can Albumin/Globulin Levels Predict Digestive Cancer Prognosis?
Does the albumin/globulin ratio (AGR) predict prognosis in digestive system cancers? No convincing conclusions have been made, say researchers from Nan Chang University in China. They conducted a meta-analysis of 15 studies involving nearly 10,000 patients. The results indicated that a low pretreatment AGR was significantly related to worse survival outcomes for patients with colorectal and other cancers of the digestive system.
Of the analyzed studies, 13 explored the association of AGR with overall survival and found that a low AGR nearly doubled the risk of death. When the researchers adjusted for cancer type, region, sample size, treatment method, and other variables, a low AGR remained a predictor for worse overall survival in colorectal, esophageal, and gastric cancer; hazard ratios (HR) equal to 2.39, 1.35, and 1.56, respectively. Two studies explored the association of a low AGR with cancer-specific survival; again a low AGR was significantly related to worse outcome (HR = 1.61).
The researchers say effects of nutrition and inflammation may underlie the prognostic value of the AGR. They refer to the “mutual promotion effect” between cancer progression and inflammation, and to the fact that cancer patients are vulnerable to cachexia, which also contributes to tumor growth. Moreover, serum albumin reflects not only the body’s nutritional status, but also, according to recent research, the inflammatory status. The serum globulin level is closely associated with immune and inflammatory status and is easily affected by dehydration and fluid retention, common to cancer patients.
Thus, the AGR, which accounts for both levels concurrently, may mirror nutritional and inflammatory indexes more precisely, the researchers say, and could be a helpful biomarker.
Source:
Guo HW, Yuan TZ, Chen JX, Zheng Y. PLoS One. 2018;13(1):e0189839.
doi: 10.1371/journal.pone.0189839.
Does the albumin/globulin ratio (AGR) predict prognosis in digestive system cancers? No convincing conclusions have been made, say researchers from Nan Chang University in China. They conducted a meta-analysis of 15 studies involving nearly 10,000 patients. The results indicated that a low pretreatment AGR was significantly related to worse survival outcomes for patients with colorectal and other cancers of the digestive system.
Of the analyzed studies, 13 explored the association of AGR with overall survival and found that a low AGR nearly doubled the risk of death. When the researchers adjusted for cancer type, region, sample size, treatment method, and other variables, a low AGR remained a predictor for worse overall survival in colorectal, esophageal, and gastric cancer; hazard ratios (HR) equal to 2.39, 1.35, and 1.56, respectively. Two studies explored the association of a low AGR with cancer-specific survival; again a low AGR was significantly related to worse outcome (HR = 1.61).
The researchers say effects of nutrition and inflammation may underlie the prognostic value of the AGR. They refer to the “mutual promotion effect” between cancer progression and inflammation, and to the fact that cancer patients are vulnerable to cachexia, which also contributes to tumor growth. Moreover, serum albumin reflects not only the body’s nutritional status, but also, according to recent research, the inflammatory status. The serum globulin level is closely associated with immune and inflammatory status and is easily affected by dehydration and fluid retention, common to cancer patients.
Thus, the AGR, which accounts for both levels concurrently, may mirror nutritional and inflammatory indexes more precisely, the researchers say, and could be a helpful biomarker.
Source:
Guo HW, Yuan TZ, Chen JX, Zheng Y. PLoS One. 2018;13(1):e0189839.
doi: 10.1371/journal.pone.0189839.
Does the albumin/globulin ratio (AGR) predict prognosis in digestive system cancers? No convincing conclusions have been made, say researchers from Nan Chang University in China. They conducted a meta-analysis of 15 studies involving nearly 10,000 patients. The results indicated that a low pretreatment AGR was significantly related to worse survival outcomes for patients with colorectal and other cancers of the digestive system.
Of the analyzed studies, 13 explored the association of AGR with overall survival and found that a low AGR nearly doubled the risk of death. When the researchers adjusted for cancer type, region, sample size, treatment method, and other variables, a low AGR remained a predictor for worse overall survival in colorectal, esophageal, and gastric cancer; hazard ratios (HR) equal to 2.39, 1.35, and 1.56, respectively. Two studies explored the association of a low AGR with cancer-specific survival; again a low AGR was significantly related to worse outcome (HR = 1.61).
The researchers say effects of nutrition and inflammation may underlie the prognostic value of the AGR. They refer to the “mutual promotion effect” between cancer progression and inflammation, and to the fact that cancer patients are vulnerable to cachexia, which also contributes to tumor growth. Moreover, serum albumin reflects not only the body’s nutritional status, but also, according to recent research, the inflammatory status. The serum globulin level is closely associated with immune and inflammatory status and is easily affected by dehydration and fluid retention, common to cancer patients.
Thus, the AGR, which accounts for both levels concurrently, may mirror nutritional and inflammatory indexes more precisely, the researchers say, and could be a helpful biomarker.
Source:
Guo HW, Yuan TZ, Chen JX, Zheng Y. PLoS One. 2018;13(1):e0189839.
doi: 10.1371/journal.pone.0189839.
Risks of MGUS persist beyond 30 years
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed. 
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.
A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.
The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.
Patients with MGUS also had a significantly shorter median survival than controls.
Researchers reported these findings in NEJM.
“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.
“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”
With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.
The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.
During that time, 147 patients progressed to another disorder, including:
- 97 to multiple myeloma
- 19 to non-Hodgkin lymphoma
- 14 to AL amyloidosis
- 13 to Waldenstrom’s macroglobulinemia
- 3 to chronic lymphocytic leukemia
- 1 to plasmacytoma.
The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.
The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.
“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.
The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).
Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.
CAR T-cell therapy on fast track in US, EU
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).
Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.
If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.
Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.
Supporting data
The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.
Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.
Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.
About priority review, accelerated assessment
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
HLF proves ‘critical’ for HSC quiescence
Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood.
Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood.
Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood.
Pearls in Dermatology: 2017
The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:
- Nail psoriasis and psoriasis on the hands and feet
- Genital wart treatment
- Isotretinoin for acne
- Cosmeceuticals for rosacea
- Surgical technique with the flexible scalpel blade
Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.
Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.
The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:
- Nail psoriasis and psoriasis on the hands and feet
- Genital wart treatment
- Isotretinoin for acne
- Cosmeceuticals for rosacea
- Surgical technique with the flexible scalpel blade
Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.
Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.
The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:
- Nail psoriasis and psoriasis on the hands and feet
- Genital wart treatment
- Isotretinoin for acne
- Cosmeceuticals for rosacea
- Surgical technique with the flexible scalpel blade
Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.
Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.
Atopic march largely attributed to genetic factors
according to a systematic review.
PhD candidate Sabria Khan and her colleagues at the Centre for Epidemiology and Biostatistics at the University of Melbourne said that the atopic march concept “asserts that allergic diseases start in early life with eczema, progress through food allergy, and culminate with hay fever and asthma.”
This systematic review of ten twin and sibling studies looked at known, measured environmental and genetic influences on the associations between the atopic phenotypes of the atopic march.
The studies of asthma and hay fever suggested that the prevalence of having both conditions was high (32%) and that they were more likely to occur together in monozygotic twins than they were in dizygotic twins. Similarly, other studies found a high phenotypic overlap between eczema and asthma and between eczema and hay fever, which was more pronounced in monozygotic twins than in dizygotic twins.
“Asthma is linked to hay fever and eczema through intermediate phenotypes like clinical measures of lung function, physiological measures of airway responsiveness and the biomarker exhaled nitric oxide, all of which are influenced by hereditary factors,” the authors said.
Overall, they concluded that genetic factors account for 75% of eczema cases, 70%-91% of asthma cases, and 72%-84% of hay fever cases, making them all highly heritable diseases.
“Our study found that the contribution of shared environmental factors to the proportion of correlation are very low (from 4% to 18%) and does not explain the familial patterns seen for asthma and hay fever,” they reported. “This finding contradicts various analyses where smoking behavior, indoor-outdoor pollution, and house dust mites were found to be significant risk factor for asthma and hay fever that are shared by siblings.”
The authors commented that preventing the onset of the atopic march, or arresting its development, could have significant public health implications. They suggested that interventions such as oral antihistamines could be introduced either before a child gets eczema or before a child with eczema goes on to develop asthma or hay fever. “Two randomized controlled trials showed moisturizing the skin can prevent mild to moderate eczema, and long-term studies are needed to see whether such intervention will prevent development of asthma and hay fever,” they said.
No conflicts of interest were declared.
SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.
according to a systematic review.
PhD candidate Sabria Khan and her colleagues at the Centre for Epidemiology and Biostatistics at the University of Melbourne said that the atopic march concept “asserts that allergic diseases start in early life with eczema, progress through food allergy, and culminate with hay fever and asthma.”
This systematic review of ten twin and sibling studies looked at known, measured environmental and genetic influences on the associations between the atopic phenotypes of the atopic march.
The studies of asthma and hay fever suggested that the prevalence of having both conditions was high (32%) and that they were more likely to occur together in monozygotic twins than they were in dizygotic twins. Similarly, other studies found a high phenotypic overlap between eczema and asthma and between eczema and hay fever, which was more pronounced in monozygotic twins than in dizygotic twins.
“Asthma is linked to hay fever and eczema through intermediate phenotypes like clinical measures of lung function, physiological measures of airway responsiveness and the biomarker exhaled nitric oxide, all of which are influenced by hereditary factors,” the authors said.
Overall, they concluded that genetic factors account for 75% of eczema cases, 70%-91% of asthma cases, and 72%-84% of hay fever cases, making them all highly heritable diseases.
“Our study found that the contribution of shared environmental factors to the proportion of correlation are very low (from 4% to 18%) and does not explain the familial patterns seen for asthma and hay fever,” they reported. “This finding contradicts various analyses where smoking behavior, indoor-outdoor pollution, and house dust mites were found to be significant risk factor for asthma and hay fever that are shared by siblings.”
The authors commented that preventing the onset of the atopic march, or arresting its development, could have significant public health implications. They suggested that interventions such as oral antihistamines could be introduced either before a child gets eczema or before a child with eczema goes on to develop asthma or hay fever. “Two randomized controlled trials showed moisturizing the skin can prevent mild to moderate eczema, and long-term studies are needed to see whether such intervention will prevent development of asthma and hay fever,” they said.
No conflicts of interest were declared.
SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.
according to a systematic review.
PhD candidate Sabria Khan and her colleagues at the Centre for Epidemiology and Biostatistics at the University of Melbourne said that the atopic march concept “asserts that allergic diseases start in early life with eczema, progress through food allergy, and culminate with hay fever and asthma.”
This systematic review of ten twin and sibling studies looked at known, measured environmental and genetic influences on the associations between the atopic phenotypes of the atopic march.
The studies of asthma and hay fever suggested that the prevalence of having both conditions was high (32%) and that they were more likely to occur together in monozygotic twins than they were in dizygotic twins. Similarly, other studies found a high phenotypic overlap between eczema and asthma and between eczema and hay fever, which was more pronounced in monozygotic twins than in dizygotic twins.
“Asthma is linked to hay fever and eczema through intermediate phenotypes like clinical measures of lung function, physiological measures of airway responsiveness and the biomarker exhaled nitric oxide, all of which are influenced by hereditary factors,” the authors said.
Overall, they concluded that genetic factors account for 75% of eczema cases, 70%-91% of asthma cases, and 72%-84% of hay fever cases, making them all highly heritable diseases.
“Our study found that the contribution of shared environmental factors to the proportion of correlation are very low (from 4% to 18%) and does not explain the familial patterns seen for asthma and hay fever,” they reported. “This finding contradicts various analyses where smoking behavior, indoor-outdoor pollution, and house dust mites were found to be significant risk factor for asthma and hay fever that are shared by siblings.”
The authors commented that preventing the onset of the atopic march, or arresting its development, could have significant public health implications. They suggested that interventions such as oral antihistamines could be introduced either before a child gets eczema or before a child with eczema goes on to develop asthma or hay fever. “Two randomized controlled trials showed moisturizing the skin can prevent mild to moderate eczema, and long-term studies are needed to see whether such intervention will prevent development of asthma and hay fever,” they said.
No conflicts of interest were declared.
SOURCE: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.
FROM ALLERGY
Key clinical point: Twin and sibling studies suggest that genetics play a far more significant role than environmental factors in the progression of atopic disease in childhood known as the “atopic march.”
Major finding: Genetic factors account for 75% of eczema, 70%-91% of asthma, and 72%-84% of hay fever.
Data source: Systematic review of ten twin and sibling studies.
Disclosures: No conflicts of interest were declared.
Source: Khan SJ et al. Allergy. 2018 Jan;73(1):17-28.
Use of non–vitamin K antagonist oral anticoagulants in the acute care, periprocedural settings
Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.
Measurement
While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.
Kidney injury
Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.
Bleeding
Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.
Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
Overdose
Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.
Intracranial hemorrhage
Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.
Ischemic stroke
Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.
The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
Procedures and surgeries
Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.
Spinal or epidural anesthesia
Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.
The bottom line
NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.
Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.
Reference
Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477
Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.
Measurement
While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.
Kidney injury
Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.
Bleeding
Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.
Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
Overdose
Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.
Intracranial hemorrhage
Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.
Ischemic stroke
Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.
The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
Procedures and surgeries
Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.
Spinal or epidural anesthesia
Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.
The bottom line
NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.
Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.
Reference
Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477
Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.
Measurement
While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.
Kidney injury
Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.
Bleeding
Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.
Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
Overdose
Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.
Intracranial hemorrhage
Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.
Ischemic stroke
Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.
The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
Procedures and surgeries
Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.
Spinal or epidural anesthesia
Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.
The bottom line
NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.
Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.
Reference
Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477
HIPEC shows survival benefit for advanced ovarian cancer
Patients with newly diagnosed advanced-stage ovarian cancer who were referred to receive three cycles of neoadjuvant chemotherapy experienced statistically significant improved recurrence-free survival and overall survival from hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery, results of a phase 3 trial showed.
After 4.7 years’ median follow-up, 89% of patients who received surgery with no HIPEC had disease recurrence or death, compared with 81% of patients treated with HIPEC (hazard ratio, 0.66; P = .003). Patients in the HIPEC cohort experienced recurrence-free survival a median of 3.5 months longer than patients who received surgery alone (10.7 months vs. 14.2 months), Willemien J. van Driel, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and her colleagues reported in the New England Journal of Medicine.
Dr. van Driel and her coauthors also reported a median 11.8 months increased overall survival (33.9 months vs. 45.7 months) for HIPEC, compared with surgery alone.
Both recurrence-free survival and overall survival remained consistently beneficial for patients in the HIPEC group across prespecified stratification factors and subgroups, including age, histology type, regional involvement, and previous surgery, according to the researchers.
They also reported that no significant differences between the two groups were noted in the incidence of adverse events of any grade. In total, grade 3 or 4 adverse events were reported by 32 patients (27%) who received HIPEC and 30 patients (25%) who received surgery (P = .76); the most common were abdominal pain, infection, and ileus.
Combination treatment with intravenous and intraperitoneal chemotherapy has been shown to prolong overall survival after primary cytoreductive surgery, according to the authors.
“Catheter-related problems, increased demands on the patient, and gastrointestinal and renal side effects have hampered the adoption of this approach in most countries,” the researchers wrote. “Hyperthermia increases the penetration of chemotherapy at the peritoneal surface and increases the sensitivity of the cancer to chemotherapy by impairing DNA repair [and] … can circumvent most of these drawbacks while maintaining its advantages.”
This research was supported by the Dutch Cancer Society. Dr. van Driel reported no relevant financial disclosures. Two other researchers reported funding from various pharmaceutical companies as well as the KFW–Dutch Cancer Foundation.
SOURCE: van Driel WJ et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMoa1708618.
Although the data reported by Dr. van Driel and her colleagues represent an important first step, the findings “should not drive changes in practice yet,” according to David R. Spriggs, MD, and Oliver Zivanovick, MD.
Dr. Spriggs and Dr. Zivanovic raised questions surrounding the efficacy of adding HIPEC to surgery and suggested that the benefit observed by Dr. van Driel and her coauthors could be attributed to several variables such as the route of intraperitoneal administration or the skill level of the attending surgeon.
Currently, certain patients with advanced ovarian cancer receive primary surgery instead of neoadjuvant chemotherapy. HIPEC does not change that approach, Dr. Spriggs and Dr. Zivanovic said.
They went on to note that further “well-designed” research could reveal other patient subgroups that warrant further investigation such as those who underwent an optimal cytoreductive procedure.
“These considerations will be important for clinical trial investigators as they focus on the positive effect of HIPEC as an intervention as compared with the effects of promising new agent combinations or immunotherapy treatments,” they wrote.
Dr. Spriggs is the associate director for clinical and translational research at Memorial Sloan Kettering Cancer Center in New York, and Dr. Zivanovic is a gynecologic oncologic surgeon at Sloan Kettering. These remarks were taken from their invited commentary on the report by Dr. van Driel and her associates. Dr. Spriggs reported that he is employed by the New England Journal of Medicine as an associate editor. Dr. Zivanovic reported no relevant financial disclosures.
SOURCE: Spriggs DR et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMe1714556.
Although the data reported by Dr. van Driel and her colleagues represent an important first step, the findings “should not drive changes in practice yet,” according to David R. Spriggs, MD, and Oliver Zivanovick, MD.
Dr. Spriggs and Dr. Zivanovic raised questions surrounding the efficacy of adding HIPEC to surgery and suggested that the benefit observed by Dr. van Driel and her coauthors could be attributed to several variables such as the route of intraperitoneal administration or the skill level of the attending surgeon.
Currently, certain patients with advanced ovarian cancer receive primary surgery instead of neoadjuvant chemotherapy. HIPEC does not change that approach, Dr. Spriggs and Dr. Zivanovic said.
They went on to note that further “well-designed” research could reveal other patient subgroups that warrant further investigation such as those who underwent an optimal cytoreductive procedure.
“These considerations will be important for clinical trial investigators as they focus on the positive effect of HIPEC as an intervention as compared with the effects of promising new agent combinations or immunotherapy treatments,” they wrote.
Dr. Spriggs is the associate director for clinical and translational research at Memorial Sloan Kettering Cancer Center in New York, and Dr. Zivanovic is a gynecologic oncologic surgeon at Sloan Kettering. These remarks were taken from their invited commentary on the report by Dr. van Driel and her associates. Dr. Spriggs reported that he is employed by the New England Journal of Medicine as an associate editor. Dr. Zivanovic reported no relevant financial disclosures.
SOURCE: Spriggs DR et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMe1714556.
Although the data reported by Dr. van Driel and her colleagues represent an important first step, the findings “should not drive changes in practice yet,” according to David R. Spriggs, MD, and Oliver Zivanovick, MD.
Dr. Spriggs and Dr. Zivanovic raised questions surrounding the efficacy of adding HIPEC to surgery and suggested that the benefit observed by Dr. van Driel and her coauthors could be attributed to several variables such as the route of intraperitoneal administration or the skill level of the attending surgeon.
Currently, certain patients with advanced ovarian cancer receive primary surgery instead of neoadjuvant chemotherapy. HIPEC does not change that approach, Dr. Spriggs and Dr. Zivanovic said.
They went on to note that further “well-designed” research could reveal other patient subgroups that warrant further investigation such as those who underwent an optimal cytoreductive procedure.
“These considerations will be important for clinical trial investigators as they focus on the positive effect of HIPEC as an intervention as compared with the effects of promising new agent combinations or immunotherapy treatments,” they wrote.
Dr. Spriggs is the associate director for clinical and translational research at Memorial Sloan Kettering Cancer Center in New York, and Dr. Zivanovic is a gynecologic oncologic surgeon at Sloan Kettering. These remarks were taken from their invited commentary on the report by Dr. van Driel and her associates. Dr. Spriggs reported that he is employed by the New England Journal of Medicine as an associate editor. Dr. Zivanovic reported no relevant financial disclosures.
SOURCE: Spriggs DR et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMe1714556.
Patients with newly diagnosed advanced-stage ovarian cancer who were referred to receive three cycles of neoadjuvant chemotherapy experienced statistically significant improved recurrence-free survival and overall survival from hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery, results of a phase 3 trial showed.
After 4.7 years’ median follow-up, 89% of patients who received surgery with no HIPEC had disease recurrence or death, compared with 81% of patients treated with HIPEC (hazard ratio, 0.66; P = .003). Patients in the HIPEC cohort experienced recurrence-free survival a median of 3.5 months longer than patients who received surgery alone (10.7 months vs. 14.2 months), Willemien J. van Driel, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and her colleagues reported in the New England Journal of Medicine.
Dr. van Driel and her coauthors also reported a median 11.8 months increased overall survival (33.9 months vs. 45.7 months) for HIPEC, compared with surgery alone.
Both recurrence-free survival and overall survival remained consistently beneficial for patients in the HIPEC group across prespecified stratification factors and subgroups, including age, histology type, regional involvement, and previous surgery, according to the researchers.
They also reported that no significant differences between the two groups were noted in the incidence of adverse events of any grade. In total, grade 3 or 4 adverse events were reported by 32 patients (27%) who received HIPEC and 30 patients (25%) who received surgery (P = .76); the most common were abdominal pain, infection, and ileus.
Combination treatment with intravenous and intraperitoneal chemotherapy has been shown to prolong overall survival after primary cytoreductive surgery, according to the authors.
“Catheter-related problems, increased demands on the patient, and gastrointestinal and renal side effects have hampered the adoption of this approach in most countries,” the researchers wrote. “Hyperthermia increases the penetration of chemotherapy at the peritoneal surface and increases the sensitivity of the cancer to chemotherapy by impairing DNA repair [and] … can circumvent most of these drawbacks while maintaining its advantages.”
This research was supported by the Dutch Cancer Society. Dr. van Driel reported no relevant financial disclosures. Two other researchers reported funding from various pharmaceutical companies as well as the KFW–Dutch Cancer Foundation.
SOURCE: van Driel WJ et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMoa1708618.
Patients with newly diagnosed advanced-stage ovarian cancer who were referred to receive three cycles of neoadjuvant chemotherapy experienced statistically significant improved recurrence-free survival and overall survival from hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery, results of a phase 3 trial showed.
After 4.7 years’ median follow-up, 89% of patients who received surgery with no HIPEC had disease recurrence or death, compared with 81% of patients treated with HIPEC (hazard ratio, 0.66; P = .003). Patients in the HIPEC cohort experienced recurrence-free survival a median of 3.5 months longer than patients who received surgery alone (10.7 months vs. 14.2 months), Willemien J. van Driel, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and her colleagues reported in the New England Journal of Medicine.
Dr. van Driel and her coauthors also reported a median 11.8 months increased overall survival (33.9 months vs. 45.7 months) for HIPEC, compared with surgery alone.
Both recurrence-free survival and overall survival remained consistently beneficial for patients in the HIPEC group across prespecified stratification factors and subgroups, including age, histology type, regional involvement, and previous surgery, according to the researchers.
They also reported that no significant differences between the two groups were noted in the incidence of adverse events of any grade. In total, grade 3 or 4 adverse events were reported by 32 patients (27%) who received HIPEC and 30 patients (25%) who received surgery (P = .76); the most common were abdominal pain, infection, and ileus.
Combination treatment with intravenous and intraperitoneal chemotherapy has been shown to prolong overall survival after primary cytoreductive surgery, according to the authors.
“Catheter-related problems, increased demands on the patient, and gastrointestinal and renal side effects have hampered the adoption of this approach in most countries,” the researchers wrote. “Hyperthermia increases the penetration of chemotherapy at the peritoneal surface and increases the sensitivity of the cancer to chemotherapy by impairing DNA repair [and] … can circumvent most of these drawbacks while maintaining its advantages.”
This research was supported by the Dutch Cancer Society. Dr. van Driel reported no relevant financial disclosures. Two other researchers reported funding from various pharmaceutical companies as well as the KFW–Dutch Cancer Foundation.
SOURCE: van Driel WJ et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMoa1708618.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Administering HIPEC during interval cytoreductive surgery lengthened survival without increasing safety risk for patients with advanced-stage ovarian cancer.
Major finding: Patients who received HIPEC experienced a median recurrence-free survival that was 3.5 months longer and overall survival that was 11.8 months longer than patients who received surgery alone.
Study details: A multicenter, open-label phase 3 trial that randomly assigned patients who had received neoadjuvant chemotherapy to receive either HIPEC or surgery alone with an endpoint of recurrence-free survival.
Disclosures: This research was supported by the Dutch Cancer Society. Dr. van Driel reported no relevant financial disclosures. Two other researchers reported funding from various pharmaceutical companies as well as the KFW–Dutch Cancer Foundation.
Source: van Driel WJ et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMoa1708618.
Thrombosis risk is elevated with myeloproliferative neoplasms
Patients with myeloproliferative neoplasms (MPNs) have a higher rate of arterial and venous thrombosis than does the general population, with the greatest risk occurring around the time of diagnosis, according to results of a retrospective study.
Hazard ratios at 3 months after diagnosis were 3.0 (95% CI, 2.7-3.4) for arterial thrombosis and 9.7 (95% CI, 7.8-12.0) for venous thrombosis, compared with matched controls, Malin Hultcrantz, MD, PhD, of the Karolinska University Hospital, Stockholm, and her coauthors reported in the Annals of Internal Medicine.
Although previous studies have suggested patients with MPNs are at increased risk for thrombotic events, this large, population-based analysis is believed to be the first study to provide estimates of excess risk compared with matched control participants.
“These results are encouraging, and we believe that further refinement of risk scoring systems (such as by including time since MPN diagnosis and biomarkers); rethinking of recommendations for younger patients with MPNs; and emerging, more effective treatments will further improve outcomes for patients with MPNs,” the researchers wrote.
The retrospective, population-based cohort study included 9,429 Swedish patients diagnosed with MPNs between 1987 and 2009 and 35,820 matched control participants. Patient follow-up through 2010 was included in the analysis.
Thrombosis risk was highest near the time of diagnosis but decreased during the following year “likely because of effective thromboprophylactic and cytoreductive treatment of the MPN;”still, the risk remained elevated, the researchers wrote.
“This novel finding underlines the importance of initiating phlebotomy as well as thromboprophylactic and cytoreductive treatment, when indicated, as soon as the MPN is diagnosed,” they added.
Arterial thrombosis hazard ratios for MPN patients, compared with control participants, were 3.0 at 3 months after diagnosis, 2.0 at 1 year, and 1.5 at 5 years. Similarly, venous thrombosis hazard ratios were 9.7 at 3 months, 4.7 at 1 year, and 3.2 at 5 years.
Thrombosis risk was elevated in all age groups and all MPN subtypes, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Of note, the study confirmed prior thrombosis and older age (60 years or older) as risk factors. Among patients with both of those risk factors, risk of thrombosis was increased 7-fold, according to the researchers.
Hazard ratios for thrombosis decreased during more recent time periods, suggesting a “positive effect” of improved treatment strategies, including increased use of aspirin as primary prophylaxis, better cardiovascular risk management, and better adherence to recommendations for cytoreductive treatment and phlebotomy, the researchers noted. Additionally, treatment with interferon and Janus kinase 2 inhibitors, such as ruxolitinib, “may be effective in further reducing risk for thrombosis,” the researchers wrote.
The study was funded by the Cancer Research Foundations of Radiumhemmet, the Swedish Research Council, and Memorial Sloan Kettering Cancer Center, among other sources. The researchers reported having no financial disclosures relevant to the study.
SOURCE: Hultcrantz M et al. Ann Intern Med. 2018. doi: 10.7326/M17-0028.
The most notable contribution of the large cohort study by Hultcrantz and her colleagues is quantification of the magnitude of thrombotic risk that MPNs confer, according to Alison R. Moliterno, MD, and Elizabeth V. Ratchford, MD.
“Hultcrantz and colleagues have opened our eyes to the magnitude of thrombotic risk MPNs bring to affected patients,” Dr. Moliterno and Dr. Ratchford wrote in an editorial in Annals of Internal Medicine. “Their study shows us that the traditional approach to assessing thrombotic risk in patients with MPNs [who are age 60 years and older, have prior thrombotic event, and have traditional cardiovascular risk factors] lacks precision and personalization.”
Both arterial and venous thrombotic events were increased throughout patients’ lifetimes, though the highest risk was around the time of MPN diagnosis. According to study results, 10% of patients had a thrombotic event in the 30 days before or after diagnosis.
“Patients and clinicians should be keenly aware of this particularly risky period, during which risk for thrombosis is similar to that in the month after a transient ischemic attack,” Dr. Moliterno and Dr. Ratchford wrote.
Unfortunately, the study did not include data on genomics, they noted. The acquired JAK2 V617F mutation, which drives MPN phenotypes, is associated with elevated inflammatory cytokines, and inflammation is a recognized risk factor for thrombosis, according to the editorial authors.
Alison R. Moliterno, MD, and Elizabeth V. Ratchford, MD, are with Johns Hopkins University, Baltimore. These comments are adapted from an accompanying editorial (Ann Intern Med. 2018. doi: 10.7326/M17-3153). The authors reported having no relevant conflicts related to the study.
The most notable contribution of the large cohort study by Hultcrantz and her colleagues is quantification of the magnitude of thrombotic risk that MPNs confer, according to Alison R. Moliterno, MD, and Elizabeth V. Ratchford, MD.
“Hultcrantz and colleagues have opened our eyes to the magnitude of thrombotic risk MPNs bring to affected patients,” Dr. Moliterno and Dr. Ratchford wrote in an editorial in Annals of Internal Medicine. “Their study shows us that the traditional approach to assessing thrombotic risk in patients with MPNs [who are age 60 years and older, have prior thrombotic event, and have traditional cardiovascular risk factors] lacks precision and personalization.”
Both arterial and venous thrombotic events were increased throughout patients’ lifetimes, though the highest risk was around the time of MPN diagnosis. According to study results, 10% of patients had a thrombotic event in the 30 days before or after diagnosis.
“Patients and clinicians should be keenly aware of this particularly risky period, during which risk for thrombosis is similar to that in the month after a transient ischemic attack,” Dr. Moliterno and Dr. Ratchford wrote.
Unfortunately, the study did not include data on genomics, they noted. The acquired JAK2 V617F mutation, which drives MPN phenotypes, is associated with elevated inflammatory cytokines, and inflammation is a recognized risk factor for thrombosis, according to the editorial authors.
Alison R. Moliterno, MD, and Elizabeth V. Ratchford, MD, are with Johns Hopkins University, Baltimore. These comments are adapted from an accompanying editorial (Ann Intern Med. 2018. doi: 10.7326/M17-3153). The authors reported having no relevant conflicts related to the study.
The most notable contribution of the large cohort study by Hultcrantz and her colleagues is quantification of the magnitude of thrombotic risk that MPNs confer, according to Alison R. Moliterno, MD, and Elizabeth V. Ratchford, MD.
“Hultcrantz and colleagues have opened our eyes to the magnitude of thrombotic risk MPNs bring to affected patients,” Dr. Moliterno and Dr. Ratchford wrote in an editorial in Annals of Internal Medicine. “Their study shows us that the traditional approach to assessing thrombotic risk in patients with MPNs [who are age 60 years and older, have prior thrombotic event, and have traditional cardiovascular risk factors] lacks precision and personalization.”
Both arterial and venous thrombotic events were increased throughout patients’ lifetimes, though the highest risk was around the time of MPN diagnosis. According to study results, 10% of patients had a thrombotic event in the 30 days before or after diagnosis.
“Patients and clinicians should be keenly aware of this particularly risky period, during which risk for thrombosis is similar to that in the month after a transient ischemic attack,” Dr. Moliterno and Dr. Ratchford wrote.
Unfortunately, the study did not include data on genomics, they noted. The acquired JAK2 V617F mutation, which drives MPN phenotypes, is associated with elevated inflammatory cytokines, and inflammation is a recognized risk factor for thrombosis, according to the editorial authors.
Alison R. Moliterno, MD, and Elizabeth V. Ratchford, MD, are with Johns Hopkins University, Baltimore. These comments are adapted from an accompanying editorial (Ann Intern Med. 2018. doi: 10.7326/M17-3153). The authors reported having no relevant conflicts related to the study.
Patients with myeloproliferative neoplasms (MPNs) have a higher rate of arterial and venous thrombosis than does the general population, with the greatest risk occurring around the time of diagnosis, according to results of a retrospective study.
Hazard ratios at 3 months after diagnosis were 3.0 (95% CI, 2.7-3.4) for arterial thrombosis and 9.7 (95% CI, 7.8-12.0) for venous thrombosis, compared with matched controls, Malin Hultcrantz, MD, PhD, of the Karolinska University Hospital, Stockholm, and her coauthors reported in the Annals of Internal Medicine.
Although previous studies have suggested patients with MPNs are at increased risk for thrombotic events, this large, population-based analysis is believed to be the first study to provide estimates of excess risk compared with matched control participants.
“These results are encouraging, and we believe that further refinement of risk scoring systems (such as by including time since MPN diagnosis and biomarkers); rethinking of recommendations for younger patients with MPNs; and emerging, more effective treatments will further improve outcomes for patients with MPNs,” the researchers wrote.
The retrospective, population-based cohort study included 9,429 Swedish patients diagnosed with MPNs between 1987 and 2009 and 35,820 matched control participants. Patient follow-up through 2010 was included in the analysis.
Thrombosis risk was highest near the time of diagnosis but decreased during the following year “likely because of effective thromboprophylactic and cytoreductive treatment of the MPN;”still, the risk remained elevated, the researchers wrote.
“This novel finding underlines the importance of initiating phlebotomy as well as thromboprophylactic and cytoreductive treatment, when indicated, as soon as the MPN is diagnosed,” they added.
Arterial thrombosis hazard ratios for MPN patients, compared with control participants, were 3.0 at 3 months after diagnosis, 2.0 at 1 year, and 1.5 at 5 years. Similarly, venous thrombosis hazard ratios were 9.7 at 3 months, 4.7 at 1 year, and 3.2 at 5 years.
Thrombosis risk was elevated in all age groups and all MPN subtypes, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Of note, the study confirmed prior thrombosis and older age (60 years or older) as risk factors. Among patients with both of those risk factors, risk of thrombosis was increased 7-fold, according to the researchers.
Hazard ratios for thrombosis decreased during more recent time periods, suggesting a “positive effect” of improved treatment strategies, including increased use of aspirin as primary prophylaxis, better cardiovascular risk management, and better adherence to recommendations for cytoreductive treatment and phlebotomy, the researchers noted. Additionally, treatment with interferon and Janus kinase 2 inhibitors, such as ruxolitinib, “may be effective in further reducing risk for thrombosis,” the researchers wrote.
The study was funded by the Cancer Research Foundations of Radiumhemmet, the Swedish Research Council, and Memorial Sloan Kettering Cancer Center, among other sources. The researchers reported having no financial disclosures relevant to the study.
SOURCE: Hultcrantz M et al. Ann Intern Med. 2018. doi: 10.7326/M17-0028.
Patients with myeloproliferative neoplasms (MPNs) have a higher rate of arterial and venous thrombosis than does the general population, with the greatest risk occurring around the time of diagnosis, according to results of a retrospective study.
Hazard ratios at 3 months after diagnosis were 3.0 (95% CI, 2.7-3.4) for arterial thrombosis and 9.7 (95% CI, 7.8-12.0) for venous thrombosis, compared with matched controls, Malin Hultcrantz, MD, PhD, of the Karolinska University Hospital, Stockholm, and her coauthors reported in the Annals of Internal Medicine.
Although previous studies have suggested patients with MPNs are at increased risk for thrombotic events, this large, population-based analysis is believed to be the first study to provide estimates of excess risk compared with matched control participants.
“These results are encouraging, and we believe that further refinement of risk scoring systems (such as by including time since MPN diagnosis and biomarkers); rethinking of recommendations for younger patients with MPNs; and emerging, more effective treatments will further improve outcomes for patients with MPNs,” the researchers wrote.
The retrospective, population-based cohort study included 9,429 Swedish patients diagnosed with MPNs between 1987 and 2009 and 35,820 matched control participants. Patient follow-up through 2010 was included in the analysis.
Thrombosis risk was highest near the time of diagnosis but decreased during the following year “likely because of effective thromboprophylactic and cytoreductive treatment of the MPN;”still, the risk remained elevated, the researchers wrote.
“This novel finding underlines the importance of initiating phlebotomy as well as thromboprophylactic and cytoreductive treatment, when indicated, as soon as the MPN is diagnosed,” they added.
Arterial thrombosis hazard ratios for MPN patients, compared with control participants, were 3.0 at 3 months after diagnosis, 2.0 at 1 year, and 1.5 at 5 years. Similarly, venous thrombosis hazard ratios were 9.7 at 3 months, 4.7 at 1 year, and 3.2 at 5 years.
Thrombosis risk was elevated in all age groups and all MPN subtypes, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Of note, the study confirmed prior thrombosis and older age (60 years or older) as risk factors. Among patients with both of those risk factors, risk of thrombosis was increased 7-fold, according to the researchers.
Hazard ratios for thrombosis decreased during more recent time periods, suggesting a “positive effect” of improved treatment strategies, including increased use of aspirin as primary prophylaxis, better cardiovascular risk management, and better adherence to recommendations for cytoreductive treatment and phlebotomy, the researchers noted. Additionally, treatment with interferon and Janus kinase 2 inhibitors, such as ruxolitinib, “may be effective in further reducing risk for thrombosis,” the researchers wrote.
The study was funded by the Cancer Research Foundations of Radiumhemmet, the Swedish Research Council, and Memorial Sloan Kettering Cancer Center, among other sources. The researchers reported having no financial disclosures relevant to the study.
SOURCE: Hultcrantz M et al. Ann Intern Med. 2018. doi: 10.7326/M17-0028.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point:
Major finding: Hazard ratios (HRs) at 3 months were 3.0 (95% confidence interval, 2.7-3.4) for arterial thrombosis and 9.7 (95% CI, 7.8-12.0) for venous thrombosis, compared with matched controls.
Study details: A Swedish retrospective, population-based study including 9,429 patients with MPNs and 35,820 matched control participants.
Disclosures: The study was funded by the Cancer Research Foundations of Radiumhemmet, the Swedish Research Council, and Memorial Sloan Kettering Cancer Center, among other sources. The researchers reported having no relevant financial disclosures.
Source: Hultcrantz M et al. Ann Intern Med. 2018. doi: 10.7326/M17-0028.
OS similar among mRCC patients enrolled in clinical trials across different geographic regions
Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.
Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.
Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.
“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”
This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.
SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.
Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.
Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.
Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.
“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”
This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.
SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.
Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.
Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.
Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.
“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”
This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.
SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.
FROM journal of global oncology
Key clinical point: The potential differences in clinical outcomes may be contributed by differences in access to clinical trials, disease biology, reporting of adverse events, and quality of care.
Major finding: Patient characteristics differed according to geographic region. No statistically significant differences in OS were observed when the United States/Canada (USC) was compared with other regions: Latin America, Asia/Oceania/Africa, and Eastern Europe.
Study details: Pooled retrospective analysis of 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.
Disclosures: The study was funded by Pfizer and in part by the Dana Farber/Harvard Cancer Center. All of the study authors reported conflicts of interest involving the sponsor, Pfizer, or other pharmaceutical companies.
Source: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.