Learn all about coding at the SVS Coding & Reimbursement Workshop, set for Oct. 19 and 20 at the Renaissance Hotel in downtown Chicago. The intensive two-day program will address 2019 updates and proposed updates, the global surgical package and how it affects billing and reimbursement and applying modifiers for streamlined reimbursement. It is designed for vascular surgeons and their support staff. Learn more, see pricing and register here.

Learn all about coding at the SVS Coding & Reimbursement Workshop, set for Oct. 19 and 20 at the Renaissance Hotel in downtown Chicago. The intensive two-day program will address 2019 updates and proposed updates, the global surgical package and how it affects billing and reimbursement and applying modifiers for streamlined reimbursement. It is designed for vascular surgeons and their support staff. Learn more, see pricing and register here.

Learn all about coding at the SVS Coding & Reimbursement Workshop, set for Oct. 19 and 20 at the Renaissance Hotel in downtown Chicago. The intensive two-day program will address 2019 updates and proposed updates, the global surgical package and how it affects billing and reimbursement and applying modifiers for streamlined reimbursement. It is designed for vascular surgeons and their support staff. Learn more, see pricing and register here.

The deadline to submit applications for the SVS Foundation Research Career Development Travel Award is Aug. 15. This award aims to develop strong leaders in vascular surgery. Awardees are assigned an SVS research mentor and are provided with funds to attend an establish research career development course.

The deadline to submit applications for the SVS Foundation Research Career Development Travel Award is Aug. 15. This award aims to develop strong leaders in vascular surgery. Awardees are assigned an SVS research mentor and are provided with funds to attend an establish research career development course.

The deadline to submit applications for the SVS Foundation Research Career Development Travel Award is Aug. 15. This award aims to develop strong leaders in vascular surgery. Awardees are assigned an SVS research mentor and are provided with funds to attend an establish research career development course.

Applications are due by Aug. 2 for the SVS International Scholars Program, which provides up to four scholarships to qualified young vascular surgeons from countries other than the United States or Canada. Awardees receive $5,000 each, to attend the 2019 Vascular Annual Meeting and to visit clinical, teaching and research facilities in the U.S. and Canada.

Applications are due by Aug. 2 for the SVS International Scholars Program, which provides up to four scholarships to qualified young vascular surgeons from countries other than the United States or Canada. Awardees receive $5,000 each, to attend the 2019 Vascular Annual Meeting and to visit clinical, teaching and research facilities in the U.S. and Canada.

Applications are due by Aug. 2 for the SVS International Scholars Program, which provides up to four scholarships to qualified young vascular surgeons from countries other than the United States or Canada. Awardees receive $5,000 each, to attend the 2019 Vascular Annual Meeting and to visit clinical, teaching and research facilities in the U.S. and Canada.

Myth: Atopic Dermatitis Does Not Start in Adulthood

Atopic dermatitis (AD) typically first appears in childhood and tends to disappear before puberty begins; however, some patients experience AD that persists into adulthood or occurs de novo. Bannister and Freeman coined the term adult-onset atopic dermatitis after reviewing 2604 cases of AD and noting that 243 patients (9%) were first diagnosed with AD at 20 years of age or older. Adult-onset AD may be its own subset of AD or childhood AD that was simply not diagnosed until adulthood or was forgotten by the patient.

Characteristically, AD presents in adults as inflammatory eczema with areas of lichenification. It could occur after a change in residence to a cold dry climate or exposure to central heating, as patients who grew up in warm, sunny, humid climates might not have had diagnosable AD in childhood or adolescence. The more common forms of adult-onset AD are hand and neck dermatitis, hand eczema, nummular eczema, or prurigo, while childhood AD often manifests in a flexural distribution. Because it is difficult to detect, adult-onset AD is diagnosed after ruling out other diseases. Diagnostic procedures, such as patch tests, skin prick tests, biopsies, or blood screenings, usually are necessary to rule out other diseases or types of eczema. Contact eczema is the first diagnostic sign of AD in adults.

Maintaining AD in the differential diagnosis for patients with clinical symptoms of pruritus and eczema is essential due to the quality of life impact of the condition. Sleep disturbance is common in adults with severe AD and treatment may help to improve sleep quality.

Hanifin suggested the following when assessing adults for AD:

• Verify diagnosis (not allergic contact dermatitis or psoriasis)
• Determine patient's history of allergies (eg, food allergy) or childhood eczema
• Obtain family history of eczema/allergies
• Evaluate if patient's occupation may impact condition (eg, contact with irritants or known contact allergens)
• Inquire about patient's childhood residence (eg, tropical climate)

Adult-onset AD is a recalcitrant condition that can be difficult to treat, and appropriately labeling/diagnosing the condition will lead to better management.

Expert Commentary

Whereas once it was the rite of the pediatric AD patient to outgrow disease, it has now become clear that resolution is not as hard a stop in atopic disease as expected. Adult-onset and persistent disease in AD is clearly a significant problem, especially in developed nations and carries a host of comorbidites. Time and enhanced research will hopefully identify interventions to  reverse the trend towards persistence into adulthood.

—Nanette B. Silverberg, MD (New York, New York)

Myth: Atopic Dermatitis Does Not Start in Adulthood

Atopic dermatitis (AD) typically first appears in childhood and tends to disappear before puberty begins; however, some patients experience AD that persists into adulthood or occurs de novo. Bannister and Freeman coined the term adult-onset atopic dermatitis after reviewing 2604 cases of AD and noting that 243 patients (9%) were first diagnosed with AD at 20 years of age or older. Adult-onset AD may be its own subset of AD or childhood AD that was simply not diagnosed until adulthood or was forgotten by the patient.

Characteristically, AD presents in adults as inflammatory eczema with areas of lichenification. It could occur after a change in residence to a cold dry climate or exposure to central heating, as patients who grew up in warm, sunny, humid climates might not have had diagnosable AD in childhood or adolescence. The more common forms of adult-onset AD are hand and neck dermatitis, hand eczema, nummular eczema, or prurigo, while childhood AD often manifests in a flexural distribution. Because it is difficult to detect, adult-onset AD is diagnosed after ruling out other diseases. Diagnostic procedures, such as patch tests, skin prick tests, biopsies, or blood screenings, usually are necessary to rule out other diseases or types of eczema. Contact eczema is the first diagnostic sign of AD in adults.

Maintaining AD in the differential diagnosis for patients with clinical symptoms of pruritus and eczema is essential due to the quality of life impact of the condition. Sleep disturbance is common in adults with severe AD and treatment may help to improve sleep quality.

Hanifin suggested the following when assessing adults for AD:

• Verify diagnosis (not allergic contact dermatitis or psoriasis)
• Determine patient's history of allergies (eg, food allergy) or childhood eczema
• Obtain family history of eczema/allergies
• Evaluate if patient's occupation may impact condition (eg, contact with irritants or known contact allergens)
• Inquire about patient's childhood residence (eg, tropical climate)

Adult-onset AD is a recalcitrant condition that can be difficult to treat, and appropriately labeling/diagnosing the condition will lead to better management.

Expert Commentary

Whereas once it was the rite of the pediatric AD patient to outgrow disease, it has now become clear that resolution is not as hard a stop in atopic disease as expected. Adult-onset and persistent disease in AD is clearly a significant problem, especially in developed nations and carries a host of comorbidites. Time and enhanced research will hopefully identify interventions to  reverse the trend towards persistence into adulthood.

—Nanette B. Silverberg, MD (New York, New York)

Myth: Atopic Dermatitis Does Not Start in Adulthood

Atopic dermatitis (AD) typically first appears in childhood and tends to disappear before puberty begins; however, some patients experience AD that persists into adulthood or occurs de novo. Bannister and Freeman coined the term adult-onset atopic dermatitis after reviewing 2604 cases of AD and noting that 243 patients (9%) were first diagnosed with AD at 20 years of age or older. Adult-onset AD may be its own subset of AD or childhood AD that was simply not diagnosed until adulthood or was forgotten by the patient.

Characteristically, AD presents in adults as inflammatory eczema with areas of lichenification. It could occur after a change in residence to a cold dry climate or exposure to central heating, as patients who grew up in warm, sunny, humid climates might not have had diagnosable AD in childhood or adolescence. The more common forms of adult-onset AD are hand and neck dermatitis, hand eczema, nummular eczema, or prurigo, while childhood AD often manifests in a flexural distribution. Because it is difficult to detect, adult-onset AD is diagnosed after ruling out other diseases. Diagnostic procedures, such as patch tests, skin prick tests, biopsies, or blood screenings, usually are necessary to rule out other diseases or types of eczema. Contact eczema is the first diagnostic sign of AD in adults.

Maintaining AD in the differential diagnosis for patients with clinical symptoms of pruritus and eczema is essential due to the quality of life impact of the condition. Sleep disturbance is common in adults with severe AD and treatment may help to improve sleep quality.

Hanifin suggested the following when assessing adults for AD:

• Verify diagnosis (not allergic contact dermatitis or psoriasis)
• Determine patient's history of allergies (eg, food allergy) or childhood eczema
• Obtain family history of eczema/allergies
• Evaluate if patient's occupation may impact condition (eg, contact with irritants or known contact allergens)
• Inquire about patient's childhood residence (eg, tropical climate)

Adult-onset AD is a recalcitrant condition that can be difficult to treat, and appropriately labeling/diagnosing the condition will lead to better management.

Expert Commentary

Whereas once it was the rite of the pediatric AD patient to outgrow disease, it has now become clear that resolution is not as hard a stop in atopic disease as expected. Adult-onset and persistent disease in AD is clearly a significant problem, especially in developed nations and carries a host of comorbidites. Time and enhanced research will hopefully identify interventions to  reverse the trend towards persistence into adulthood.

—Nanette B. Silverberg, MD (New York, New York)

Click here to view the articles published in July 2018.

Click here to view the articles published in July 2018.

Click here to view the articles published in July 2018.

Cancer death rates continue to decline in the US in all major racial and ethnic groups, according to the National Cancer Institute’s (NCI) latest Annual Report to the Nation on the Status of Cancer. The data are an “encouraging indicator of progress” in cancer research, says NCI Director Ned Sharpless, MD. “It’s clear that interventions are having an impact.”

Overall incidence, or rates of new cancers, dropped by 1.8% in men and 1.4% in women from 1999 to 2015. Between 2011 and 2015, death rates dropped for 11 of the 18 most common cancer types in men and 14 of the 20 most common types in women. The researchers say the “significant declines” also hold “significant differences” in rate by sex, race, and ethnicity. For example, black men and white women had the highest incidence rates, and black men and black women had the highest death rates.

However, over the same period, death rates for cancers of the liver, pancreas, and brain and nervous system rose in both men and women. Death rates for cancer of the uterus rose (the researchers say obesity is thought to be a contributing factor) and death rates for cancers of the oral cavity and pharynx and soft tissue increased in men, perhaps associated with human papillomavirus infection.

In a companion study, when researchers explored prostate cancer trends in more detail they found overall prostate cancer incidence rates declined an average of 6.5% each year between 2007 and 2014, from 163 new cases per 100,000 men to 104 new cases. Still, after a 2-decade steady decline, rates leveled off. Incidence of distant disease rose from 7.8 new cases per 100,000 to 9.2, but there was no increase in the rates of cases with aggressive histologic grade.

Interestingly, the researchers also report a decline in recent prostate-specific antigen screening between 2010 and 2013 national surveys. “The increase in late-stage disease and the flattening of the mortality trended occurred contemporaneously with the observed decrease in PSA screening,” said Serban Negoita, MD, DrPH, of NCI’s Surveillance Research Program. However, while “suggestive,” Negoita adds, their observation does not demonstrate causality: many factors contribute to incidence and mortality, such as improvements in staging and treating cancer.

Cancer death rates continue to decline in the US in all major racial and ethnic groups, according to the National Cancer Institute’s (NCI) latest Annual Report to the Nation on the Status of Cancer. The data are an “encouraging indicator of progress” in cancer research, says NCI Director Ned Sharpless, MD. “It’s clear that interventions are having an impact.”

Overall incidence, or rates of new cancers, dropped by 1.8% in men and 1.4% in women from 1999 to 2015. Between 2011 and 2015, death rates dropped for 11 of the 18 most common cancer types in men and 14 of the 20 most common types in women. The researchers say the “significant declines” also hold “significant differences” in rate by sex, race, and ethnicity. For example, black men and white women had the highest incidence rates, and black men and black women had the highest death rates.

However, over the same period, death rates for cancers of the liver, pancreas, and brain and nervous system rose in both men and women. Death rates for cancer of the uterus rose (the researchers say obesity is thought to be a contributing factor) and death rates for cancers of the oral cavity and pharynx and soft tissue increased in men, perhaps associated with human papillomavirus infection.

In a companion study, when researchers explored prostate cancer trends in more detail they found overall prostate cancer incidence rates declined an average of 6.5% each year between 2007 and 2014, from 163 new cases per 100,000 men to 104 new cases. Still, after a 2-decade steady decline, rates leveled off. Incidence of distant disease rose from 7.8 new cases per 100,000 to 9.2, but there was no increase in the rates of cases with aggressive histologic grade.

Interestingly, the researchers also report a decline in recent prostate-specific antigen screening between 2010 and 2013 national surveys. “The increase in late-stage disease and the flattening of the mortality trended occurred contemporaneously with the observed decrease in PSA screening,” said Serban Negoita, MD, DrPH, of NCI’s Surveillance Research Program. However, while “suggestive,” Negoita adds, their observation does not demonstrate causality: many factors contribute to incidence and mortality, such as improvements in staging and treating cancer.

Cancer death rates continue to decline in the US in all major racial and ethnic groups, according to the National Cancer Institute’s (NCI) latest Annual Report to the Nation on the Status of Cancer. The data are an “encouraging indicator of progress” in cancer research, says NCI Director Ned Sharpless, MD. “It’s clear that interventions are having an impact.”

Overall incidence, or rates of new cancers, dropped by 1.8% in men and 1.4% in women from 1999 to 2015. Between 2011 and 2015, death rates dropped for 11 of the 18 most common cancer types in men and 14 of the 20 most common types in women. The researchers say the “significant declines” also hold “significant differences” in rate by sex, race, and ethnicity. For example, black men and white women had the highest incidence rates, and black men and black women had the highest death rates.

However, over the same period, death rates for cancers of the liver, pancreas, and brain and nervous system rose in both men and women. Death rates for cancer of the uterus rose (the researchers say obesity is thought to be a contributing factor) and death rates for cancers of the oral cavity and pharynx and soft tissue increased in men, perhaps associated with human papillomavirus infection.

In a companion study, when researchers explored prostate cancer trends in more detail they found overall prostate cancer incidence rates declined an average of 6.5% each year between 2007 and 2014, from 163 new cases per 100,000 men to 104 new cases. Still, after a 2-decade steady decline, rates leveled off. Incidence of distant disease rose from 7.8 new cases per 100,000 to 9.2, but there was no increase in the rates of cases with aggressive histologic grade.

Interestingly, the researchers also report a decline in recent prostate-specific antigen screening between 2010 and 2013 national surveys. “The increase in late-stage disease and the flattening of the mortality trended occurred contemporaneously with the observed decrease in PSA screening,” said Serban Negoita, MD, DrPH, of NCI’s Surveillance Research Program. However, while “suggestive,” Negoita adds, their observation does not demonstrate causality: many factors contribute to incidence and mortality, such as improvements in staging and treating cancer.

There is significant variation among the civilian, active-duty, and veteran populations in regard to dermatologic conditions. Civilians most frequently visit a specialist with complaints of eczema, dermatitis, acne, and other benign conditions. Among active-duty service members, infections and allergic bite reactions are the most common reasons for a trip to a health care facility. In contrast, veterans are more likely to be diagnosed with precancerous skin conditions or to receive a screening for malignant skin cancers.

Click here to continue reading.

There is significant variation among the civilian, active-duty, and veteran populations in regard to dermatologic conditions. Civilians most frequently visit a specialist with complaints of eczema, dermatitis, acne, and other benign conditions. Among active-duty service members, infections and allergic bite reactions are the most common reasons for a trip to a health care facility. In contrast, veterans are more likely to be diagnosed with precancerous skin conditions or to receive a screening for malignant skin cancers.

Click here to continue reading.

There is significant variation among the civilian, active-duty, and veteran populations in regard to dermatologic conditions. Civilians most frequently visit a specialist with complaints of eczema, dermatitis, acne, and other benign conditions. Among active-duty service members, infections and allergic bite reactions are the most common reasons for a trip to a health care facility. In contrast, veterans are more likely to be diagnosed with precancerous skin conditions or to receive a screening for malignant skin cancers.

Click here to continue reading.

Image from Jens Langner

In the PETAL trial, treatment intensification based on results of an interim positron emission tomography (PET) scan did not improve survival outcomes for patients with aggressive lymphomas.

PET-positive patients did not benefit by switching from R-CHOP to a more intensive chemotherapy regimen.

PET-negative patients did not benefit from 2 additional cycles of rituximab after R-CHOP.

These results were published in the Journal of Clinical Oncology.

PETAL was a randomized trial of patients with newly diagnosed T- or B-cell lymphomas.

Patients received 2 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)—plus rituximab (R-CHOP) in CD20-positive lymphomas—followed by a PET scan.

PET-positive patients were randomized to receive 6 additional cycles of R-CHOP or 6 blocks of an intensive protocol used to treat Burkitt lymphoma. This protocol consisted of high-dose methotrexate, cytarabine, hyperfractionated cyclophosphamide and ifosfamide, split-dose doxorubicin and etoposide, vincristine, vindesine, and dexamethasone.

PET-negative patients with CD20-positive lymphomas were randomized to receive 4 additional cycles of R-CHOP or 4 additional cycles of R-CHOP followed by 2 more doses of rituximab.

Among patients with T-cell lymphomas, only PET-positive individuals underwent randomization. PET-negative patients received CHOP. Patients with CD20-positive T-cell lymphomas also received rituximab.

PET-positive results

Of the PET-positive patients (108/862), 52 were randomized to receive 6 additional cycles of R-CHOP, and 56 were randomized to 6 cycles of the Burkitt protocol.

In general, survival rates were similar regardless of treatment. The 2-year overall survival (OS) rate was 63.6% for patients who received R-CHOP and 55.4% for those who received the more intensive protocol.

Two-year progression-free survival (PFS) rates were 49.4% and 43.1%, respectively. Two-year event-free survival (EFS) rates were 42.0% and 31.6%, respectively.

Among patients with diffuse large B-cell lymphoma (DLBCL), the OS rate was 64.8% for patients who received R-CHOP and 47.1% for those on the Burkitt protocol. PFS rates were 55.5% and 41.4%, respectively.

There was a significant difference in EFS rates among the DLBCL patients—52.4% in the R-CHOP arm and 28.3% in the intensive arm (P=0.0186).

Among T-cell lymphoma patients, the OS rate was 22.2% in the R-CHOP arm and 30.0% in the intensive arm. The PFS rates were 12.7% and 30%, respectively. The EFS rates were the same as the PFS rates.

Overall, patients who received the Burkitt protocol had significantly higher rates of grade 3/4 hematologic toxicities, infection, and mucositis.

PET-negative results

Of 754 PET-negative patients, 697 had CD20-positive lymphomas, and 255 of those patients (all with B-cell lymphomas) underwent randomization.

There were 129 patients who were randomized to receive 6 cycles of R-CHOP (2 before and 4 after randomization) and 126 who were randomized to receive 6 cycles of R-CHOP plus 2 additional cycles of rituximab.

Again, survival rates were similar regardless of treatment.

The 2-year OS was 88.2% for patients who received only R-CHOP and 87.2% for those with additional rituximab exposure. PFS rates were 82.0% and 77.5%, respectively. EFS rates were 76.4% and 73.5%, respectively.

In the DLBCL patients, the OS rate was 88.5% in the R-CHOP arm and 85.8% in the intensive arm. PFS rates were 82.3% and 77.7%, respectively. EFS rates were 72.6% and 78.9%, respectively.

As increasing the dose of rituximab did not improve outcomes, the investigators concluded that 6 cycles of R-CHOP should be the standard of care for these patients.

The team also said interim PET scanning is “a powerful tool” for identifying chemotherapy-resistant lymphomas, and PET-positive patients may be candidates for immunologic treatment approaches.

Image from Jens Langner

In the PETAL trial, treatment intensification based on results of an interim positron emission tomography (PET) scan did not improve survival outcomes for patients with aggressive lymphomas.

PET-positive patients did not benefit by switching from R-CHOP to a more intensive chemotherapy regimen.

PET-negative patients did not benefit from 2 additional cycles of rituximab after R-CHOP.

These results were published in the Journal of Clinical Oncology.

PETAL was a randomized trial of patients with newly diagnosed T- or B-cell lymphomas.

Patients received 2 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)—plus rituximab (R-CHOP) in CD20-positive lymphomas—followed by a PET scan.

PET-positive patients were randomized to receive 6 additional cycles of R-CHOP or 6 blocks of an intensive protocol used to treat Burkitt lymphoma. This protocol consisted of high-dose methotrexate, cytarabine, hyperfractionated cyclophosphamide and ifosfamide, split-dose doxorubicin and etoposide, vincristine, vindesine, and dexamethasone.

PET-negative patients with CD20-positive lymphomas were randomized to receive 4 additional cycles of R-CHOP or 4 additional cycles of R-CHOP followed by 2 more doses of rituximab.

Among patients with T-cell lymphomas, only PET-positive individuals underwent randomization. PET-negative patients received CHOP. Patients with CD20-positive T-cell lymphomas also received rituximab.

PET-positive results

Of the PET-positive patients (108/862), 52 were randomized to receive 6 additional cycles of R-CHOP, and 56 were randomized to 6 cycles of the Burkitt protocol.

In general, survival rates were similar regardless of treatment. The 2-year overall survival (OS) rate was 63.6% for patients who received R-CHOP and 55.4% for those who received the more intensive protocol.

Two-year progression-free survival (PFS) rates were 49.4% and 43.1%, respectively. Two-year event-free survival (EFS) rates were 42.0% and 31.6%, respectively.

Among patients with diffuse large B-cell lymphoma (DLBCL), the OS rate was 64.8% for patients who received R-CHOP and 47.1% for those on the Burkitt protocol. PFS rates were 55.5% and 41.4%, respectively.

There was a significant difference in EFS rates among the DLBCL patients—52.4% in the R-CHOP arm and 28.3% in the intensive arm (P=0.0186).

Among T-cell lymphoma patients, the OS rate was 22.2% in the R-CHOP arm and 30.0% in the intensive arm. The PFS rates were 12.7% and 30%, respectively. The EFS rates were the same as the PFS rates.

Overall, patients who received the Burkitt protocol had significantly higher rates of grade 3/4 hematologic toxicities, infection, and mucositis.

PET-negative results

Of 754 PET-negative patients, 697 had CD20-positive lymphomas, and 255 of those patients (all with B-cell lymphomas) underwent randomization.

There were 129 patients who were randomized to receive 6 cycles of R-CHOP (2 before and 4 after randomization) and 126 who were randomized to receive 6 cycles of R-CHOP plus 2 additional cycles of rituximab.

Again, survival rates were similar regardless of treatment.

The 2-year OS was 88.2% for patients who received only R-CHOP and 87.2% for those with additional rituximab exposure. PFS rates were 82.0% and 77.5%, respectively. EFS rates were 76.4% and 73.5%, respectively.

In the DLBCL patients, the OS rate was 88.5% in the R-CHOP arm and 85.8% in the intensive arm. PFS rates were 82.3% and 77.7%, respectively. EFS rates were 72.6% and 78.9%, respectively.

As increasing the dose of rituximab did not improve outcomes, the investigators concluded that 6 cycles of R-CHOP should be the standard of care for these patients.

The team also said interim PET scanning is “a powerful tool” for identifying chemotherapy-resistant lymphomas, and PET-positive patients may be candidates for immunologic treatment approaches.

Image from Jens Langner

In the PETAL trial, treatment intensification based on results of an interim positron emission tomography (PET) scan did not improve survival outcomes for patients with aggressive lymphomas.

PET-positive patients did not benefit by switching from R-CHOP to a more intensive chemotherapy regimen.

PET-negative patients did not benefit from 2 additional cycles of rituximab after R-CHOP.

These results were published in the Journal of Clinical Oncology.

PETAL was a randomized trial of patients with newly diagnosed T- or B-cell lymphomas.

Patients received 2 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)—plus rituximab (R-CHOP) in CD20-positive lymphomas—followed by a PET scan.

PET-positive patients were randomized to receive 6 additional cycles of R-CHOP or 6 blocks of an intensive protocol used to treat Burkitt lymphoma. This protocol consisted of high-dose methotrexate, cytarabine, hyperfractionated cyclophosphamide and ifosfamide, split-dose doxorubicin and etoposide, vincristine, vindesine, and dexamethasone.

PET-negative patients with CD20-positive lymphomas were randomized to receive 4 additional cycles of R-CHOP or 4 additional cycles of R-CHOP followed by 2 more doses of rituximab.

Among patients with T-cell lymphomas, only PET-positive individuals underwent randomization. PET-negative patients received CHOP. Patients with CD20-positive T-cell lymphomas also received rituximab.

PET-positive results

Of the PET-positive patients (108/862), 52 were randomized to receive 6 additional cycles of R-CHOP, and 56 were randomized to 6 cycles of the Burkitt protocol.

In general, survival rates were similar regardless of treatment. The 2-year overall survival (OS) rate was 63.6% for patients who received R-CHOP and 55.4% for those who received the more intensive protocol.

Two-year progression-free survival (PFS) rates were 49.4% and 43.1%, respectively. Two-year event-free survival (EFS) rates were 42.0% and 31.6%, respectively.

Among patients with diffuse large B-cell lymphoma (DLBCL), the OS rate was 64.8% for patients who received R-CHOP and 47.1% for those on the Burkitt protocol. PFS rates were 55.5% and 41.4%, respectively.

There was a significant difference in EFS rates among the DLBCL patients—52.4% in the R-CHOP arm and 28.3% in the intensive arm (P=0.0186).

Among T-cell lymphoma patients, the OS rate was 22.2% in the R-CHOP arm and 30.0% in the intensive arm. The PFS rates were 12.7% and 30%, respectively. The EFS rates were the same as the PFS rates.

Overall, patients who received the Burkitt protocol had significantly higher rates of grade 3/4 hematologic toxicities, infection, and mucositis.

PET-negative results

Of 754 PET-negative patients, 697 had CD20-positive lymphomas, and 255 of those patients (all with B-cell lymphomas) underwent randomization.

There were 129 patients who were randomized to receive 6 cycles of R-CHOP (2 before and 4 after randomization) and 126 who were randomized to receive 6 cycles of R-CHOP plus 2 additional cycles of rituximab.

Again, survival rates were similar regardless of treatment.

The 2-year OS was 88.2% for patients who received only R-CHOP and 87.2% for those with additional rituximab exposure. PFS rates were 82.0% and 77.5%, respectively. EFS rates were 76.4% and 73.5%, respectively.

In the DLBCL patients, the OS rate was 88.5% in the R-CHOP arm and 85.8% in the intensive arm. PFS rates were 82.3% and 77.7%, respectively. EFS rates were 72.6% and 78.9%, respectively.

As increasing the dose of rituximab did not improve outcomes, the investigators concluded that 6 cycles of R-CHOP should be the standard of care for these patients.

The team also said interim PET scanning is “a powerful tool” for identifying chemotherapy-resistant lymphomas, and PET-positive patients may be candidates for immunologic treatment approaches.

Megakaryocytes in the bone marrow

Turbulence promotes large-scale production of functional platelets from human induced pluripotent stem cells (hiPSCs), according to research published in Cell.

Exposure to turbulent energy in a bioreactor stimulated hiPSC-derived megakaryocytes to produce 100 billion platelets.

Transfusion of these platelets in 2 animal models promoted blood clotting and prevented bleeding just as well as platelets from human donors.

“The discovery of turbulent energy provides a new physical mechanism and ex vivo production strategy for the generation of platelets that should impact clinical-scale cell therapies for regenerative medicine,” said study author Koji Eto, MD, PhD, of Kyoto University in Japan.

Previous attempts to generate platelets from hiPSC-derived megakaryocytes failed to achieve a scale suitable for clinical manufacturing.

While searching for a solution to this problem, Dr Eto and his colleagues noticed that hiPSC-derived megakaryocytes produced more platelets when being rotated in a flask than under static conditions in a petri dish.

This observation suggested that physical stress from horizontal shaking under liquid conditions enhances platelet generation.

Following up on this discovery, the researchers tested a rocking-bag-based bioreactor followed by a new microfluidic system with a flow chamber and multiple pillars, but these devices generated fewer than 20 platelets per hiPSC-derived megakaryocyte.

To examine the ideal physical conditions for generating platelets, Dr Eto and his team conducted live-imaging studies of mouse bone marrow.

These experiments revealed that megakaryocytes release platelets only when they are exposed to turbulent blood flow. In support of this idea, simulations confirmed that the bioreactor and microfluidic system the researchers previously tested lacked sufficient turbulent energy.

“The discovery of the crucial role of turbulence in platelet production significantly extends past research showing that shear stress from blood flow is also a key physical factor in this process,” Dr Eto said.

“Our findings also show that iPS cells are not the end-all be-all for producing platelets. Understanding fluid dynamics in addition to iPS cell technology was necessary for our discovery.”

After testing various devices, the researchers discovered that large-scale production of high-quality platelets was possible using a bioreactor called VerMES. This system consists of 2 oval-shaped, horizontally oriented mixing blades that generate relatively high levels of turbulence by moving up and down in a cylinder.

With the optimal level of turbulent energy and shear stress created by the blade motion, the hiPSC-derived megakaryocytes generated 100 billion platelets—enough to satisfy clinical requirements.

Transfusion experiments in 2 animal models of thrombocytopenia showed that these platelets perform similarly to platelets from human donors. Both types of platelets promoted blood clotting and reduced bleeding times to a comparable extent after ear vein incisions in rabbits and tail artery punctures in mice.

Dr Eto and his team are taking this work further by designing automated protocols, lowering manufacturing costs, and optimizing platelet yields. They are also developing universal platelets lacking human leukocyte antigens in order to reduce the risk of immune-mediated transfusion reactions.

“We expect clinical trials to begin within a year or two,” Dr Eto said. “We believe these findings will be a last scientific step to receiving permission for clinical trials using our platelets.”

Megakaryocytes in the bone marrow

Turbulence promotes large-scale production of functional platelets from human induced pluripotent stem cells (hiPSCs), according to research published in Cell.

Exposure to turbulent energy in a bioreactor stimulated hiPSC-derived megakaryocytes to produce 100 billion platelets.

Transfusion of these platelets in 2 animal models promoted blood clotting and prevented bleeding just as well as platelets from human donors.

“The discovery of turbulent energy provides a new physical mechanism and ex vivo production strategy for the generation of platelets that should impact clinical-scale cell therapies for regenerative medicine,” said study author Koji Eto, MD, PhD, of Kyoto University in Japan.

Previous attempts to generate platelets from hiPSC-derived megakaryocytes failed to achieve a scale suitable for clinical manufacturing.

While searching for a solution to this problem, Dr Eto and his colleagues noticed that hiPSC-derived megakaryocytes produced more platelets when being rotated in a flask than under static conditions in a petri dish.

This observation suggested that physical stress from horizontal shaking under liquid conditions enhances platelet generation.

Following up on this discovery, the researchers tested a rocking-bag-based bioreactor followed by a new microfluidic system with a flow chamber and multiple pillars, but these devices generated fewer than 20 platelets per hiPSC-derived megakaryocyte.

To examine the ideal physical conditions for generating platelets, Dr Eto and his team conducted live-imaging studies of mouse bone marrow.

These experiments revealed that megakaryocytes release platelets only when they are exposed to turbulent blood flow. In support of this idea, simulations confirmed that the bioreactor and microfluidic system the researchers previously tested lacked sufficient turbulent energy.

“The discovery of the crucial role of turbulence in platelet production significantly extends past research showing that shear stress from blood flow is also a key physical factor in this process,” Dr Eto said.

“Our findings also show that iPS cells are not the end-all be-all for producing platelets. Understanding fluid dynamics in addition to iPS cell technology was necessary for our discovery.”

After testing various devices, the researchers discovered that large-scale production of high-quality platelets was possible using a bioreactor called VerMES. This system consists of 2 oval-shaped, horizontally oriented mixing blades that generate relatively high levels of turbulence by moving up and down in a cylinder.

With the optimal level of turbulent energy and shear stress created by the blade motion, the hiPSC-derived megakaryocytes generated 100 billion platelets—enough to satisfy clinical requirements.

Transfusion experiments in 2 animal models of thrombocytopenia showed that these platelets perform similarly to platelets from human donors. Both types of platelets promoted blood clotting and reduced bleeding times to a comparable extent after ear vein incisions in rabbits and tail artery punctures in mice.

Dr Eto and his team are taking this work further by designing automated protocols, lowering manufacturing costs, and optimizing platelet yields. They are also developing universal platelets lacking human leukocyte antigens in order to reduce the risk of immune-mediated transfusion reactions.

“We expect clinical trials to begin within a year or two,” Dr Eto said. “We believe these findings will be a last scientific step to receiving permission for clinical trials using our platelets.”

Megakaryocytes in the bone marrow

Turbulence promotes large-scale production of functional platelets from human induced pluripotent stem cells (hiPSCs), according to research published in Cell.

Exposure to turbulent energy in a bioreactor stimulated hiPSC-derived megakaryocytes to produce 100 billion platelets.

Transfusion of these platelets in 2 animal models promoted blood clotting and prevented bleeding just as well as platelets from human donors.

“The discovery of turbulent energy provides a new physical mechanism and ex vivo production strategy for the generation of platelets that should impact clinical-scale cell therapies for regenerative medicine,” said study author Koji Eto, MD, PhD, of Kyoto University in Japan.

Previous attempts to generate platelets from hiPSC-derived megakaryocytes failed to achieve a scale suitable for clinical manufacturing.

While searching for a solution to this problem, Dr Eto and his colleagues noticed that hiPSC-derived megakaryocytes produced more platelets when being rotated in a flask than under static conditions in a petri dish.

This observation suggested that physical stress from horizontal shaking under liquid conditions enhances platelet generation.

Following up on this discovery, the researchers tested a rocking-bag-based bioreactor followed by a new microfluidic system with a flow chamber and multiple pillars, but these devices generated fewer than 20 platelets per hiPSC-derived megakaryocyte.

To examine the ideal physical conditions for generating platelets, Dr Eto and his team conducted live-imaging studies of mouse bone marrow.

These experiments revealed that megakaryocytes release platelets only when they are exposed to turbulent blood flow. In support of this idea, simulations confirmed that the bioreactor and microfluidic system the researchers previously tested lacked sufficient turbulent energy.

“The discovery of the crucial role of turbulence in platelet production significantly extends past research showing that shear stress from blood flow is also a key physical factor in this process,” Dr Eto said.

“Our findings also show that iPS cells are not the end-all be-all for producing platelets. Understanding fluid dynamics in addition to iPS cell technology was necessary for our discovery.”

After testing various devices, the researchers discovered that large-scale production of high-quality platelets was possible using a bioreactor called VerMES. This system consists of 2 oval-shaped, horizontally oriented mixing blades that generate relatively high levels of turbulence by moving up and down in a cylinder.

With the optimal level of turbulent energy and shear stress created by the blade motion, the hiPSC-derived megakaryocytes generated 100 billion platelets—enough to satisfy clinical requirements.

Transfusion experiments in 2 animal models of thrombocytopenia showed that these platelets perform similarly to platelets from human donors. Both types of platelets promoted blood clotting and reduced bleeding times to a comparable extent after ear vein incisions in rabbits and tail artery punctures in mice.

Dr Eto and his team are taking this work further by designing automated protocols, lowering manufacturing costs, and optimizing platelet yields. They are also developing universal platelets lacking human leukocyte antigens in order to reduce the risk of immune-mediated transfusion reactions.

“We expect clinical trials to begin within a year or two,” Dr Eto said. “We believe these findings will be a last scientific step to receiving permission for clinical trials using our platelets.”

Research Hospital

New research has shown that childhood cancer survivors (CCSs) with certain germline mutations have higher relative rates (RRs) of secondary neoplasms (SNs) later in life.

Mutation carriers had significantly higher rates of breast cancer and sarcoma if they had received radiation to treat their initial cancer.

Among CCSs who did not receive radiation, the mutations were associated with increased rates of any SN, breast cancer, nonmelanoma skin cancer, and 2 or more histologically distinct SNs.

These findings were reported in the Journal of Clinical Oncology.

Researchers sequenced samples from 3006 CCSs who were at least 5 years from their initial cancer diagnosis as well as 341 samples from cancer-free control subjects.

All subjects were participants in the St. Jude Lifetime Cohort Study, a retrospective study with prospective clinical follow-up.

Thirty-five percent of the CCSs had survived leukemia, and 19% had survived lymphoma.

The CCS’s median age at childhood cancer diagnosis was 7.1 years, and the median follow-up was 28 years. The controls had a median age of 36.4 at follow-up.

Results

There were 1120 SNs diagnosed in 439 CCSs (14.6%). Ninety-one CCSs developed 2 or more histologically distinct SNs. The median time to SN diagnosis was 25.6 years

Non-melanoma skin cancer (580 in 159 CCSs), meningiomas (233 in 102 CCSs), thyroid cancer (67 in 67 CCSs), and breast cancer (60 in 53 CCSs) were among the SNs reported.

There were 15 neoplasms recorded in the control group—14 cases of non-melanoma skin cancer and 1 meningioma.

Pathogenic or likely pathogenic (P/LP) mutations in 32 genes were reported in 175 CCSs. The prevalence in CCSs (5.8%) was nearly 10-fold higher than in controls (0.6%).

The most commonly mutated genes in CCSs were RB1 (n=43), NF1 (n=22), BRCA2 (n=14), BRCA1 (n=12), and TP53 (n=10).

In a multivariable analysis adjusted for sex, age at primary cancer diagnosis, and treatment, P/LP mutation carriers had a significantly higher rate of any SN (RR=1.8).

The rate of subsequent breast cancer was significantly increased among females with a P/LP mutation (RR= 9.4), recipients of chest radiation (RR=7.9), and those with higher anthracycline exposure (RR=2.4).

The rate of subsequent sarcoma was significantly increased for mutation carriers (RR=10.9) and CCSs with greater exposure to alkylating agents (RR=3.8).

Among irradiated CCSs, P/LP mutations were associated with significantly increased rates of breast cancer (RR=13.9) and sarcoma (RR=10.6)

Among non-irradiated CCSs, P/LP mutations were associated with significantly increased rates of any SN (RR=4.7), breast cancer (RR=7.7), nonmelanoma skin cancer (RR=11.0), and 2 or more histologically distinct SNs (RR=18.6).

The researchers said the higher risk of SNs in CCSs with P/LP mutations suggests all CCSs should be referred for genetic counseling.

Research Hospital

New research has shown that childhood cancer survivors (CCSs) with certain germline mutations have higher relative rates (RRs) of secondary neoplasms (SNs) later in life.

Mutation carriers had significantly higher rates of breast cancer and sarcoma if they had received radiation to treat their initial cancer.

Among CCSs who did not receive radiation, the mutations were associated with increased rates of any SN, breast cancer, nonmelanoma skin cancer, and 2 or more histologically distinct SNs.

These findings were reported in the Journal of Clinical Oncology.

Researchers sequenced samples from 3006 CCSs who were at least 5 years from their initial cancer diagnosis as well as 341 samples from cancer-free control subjects.

All subjects were participants in the St. Jude Lifetime Cohort Study, a retrospective study with prospective clinical follow-up.

Thirty-five percent of the CCSs had survived leukemia, and 19% had survived lymphoma.

The CCS’s median age at childhood cancer diagnosis was 7.1 years, and the median follow-up was 28 years. The controls had a median age of 36.4 at follow-up.

Results

There were 1120 SNs diagnosed in 439 CCSs (14.6%). Ninety-one CCSs developed 2 or more histologically distinct SNs. The median time to SN diagnosis was 25.6 years

Non-melanoma skin cancer (580 in 159 CCSs), meningiomas (233 in 102 CCSs), thyroid cancer (67 in 67 CCSs), and breast cancer (60 in 53 CCSs) were among the SNs reported.

There were 15 neoplasms recorded in the control group—14 cases of non-melanoma skin cancer and 1 meningioma.

Pathogenic or likely pathogenic (P/LP) mutations in 32 genes were reported in 175 CCSs. The prevalence in CCSs (5.8%) was nearly 10-fold higher than in controls (0.6%).

The most commonly mutated genes in CCSs were RB1 (n=43), NF1 (n=22), BRCA2 (n=14), BRCA1 (n=12), and TP53 (n=10).

In a multivariable analysis adjusted for sex, age at primary cancer diagnosis, and treatment, P/LP mutation carriers had a significantly higher rate of any SN (RR=1.8).

The rate of subsequent breast cancer was significantly increased among females with a P/LP mutation (RR= 9.4), recipients of chest radiation (RR=7.9), and those with higher anthracycline exposure (RR=2.4).

The rate of subsequent sarcoma was significantly increased for mutation carriers (RR=10.9) and CCSs with greater exposure to alkylating agents (RR=3.8).

Among irradiated CCSs, P/LP mutations were associated with significantly increased rates of breast cancer (RR=13.9) and sarcoma (RR=10.6)

Among non-irradiated CCSs, P/LP mutations were associated with significantly increased rates of any SN (RR=4.7), breast cancer (RR=7.7), nonmelanoma skin cancer (RR=11.0), and 2 or more histologically distinct SNs (RR=18.6).

The researchers said the higher risk of SNs in CCSs with P/LP mutations suggests all CCSs should be referred for genetic counseling.

Research Hospital

New research has shown that childhood cancer survivors (CCSs) with certain germline mutations have higher relative rates (RRs) of secondary neoplasms (SNs) later in life.

Mutation carriers had significantly higher rates of breast cancer and sarcoma if they had received radiation to treat their initial cancer.

Among CCSs who did not receive radiation, the mutations were associated with increased rates of any SN, breast cancer, nonmelanoma skin cancer, and 2 or more histologically distinct SNs.

These findings were reported in the Journal of Clinical Oncology.

Researchers sequenced samples from 3006 CCSs who were at least 5 years from their initial cancer diagnosis as well as 341 samples from cancer-free control subjects.

All subjects were participants in the St. Jude Lifetime Cohort Study, a retrospective study with prospective clinical follow-up.

Thirty-five percent of the CCSs had survived leukemia, and 19% had survived lymphoma.

The CCS’s median age at childhood cancer diagnosis was 7.1 years, and the median follow-up was 28 years. The controls had a median age of 36.4 at follow-up.

Results

There were 1120 SNs diagnosed in 439 CCSs (14.6%). Ninety-one CCSs developed 2 or more histologically distinct SNs. The median time to SN diagnosis was 25.6 years

Non-melanoma skin cancer (580 in 159 CCSs), meningiomas (233 in 102 CCSs), thyroid cancer (67 in 67 CCSs), and breast cancer (60 in 53 CCSs) were among the SNs reported.

There were 15 neoplasms recorded in the control group—14 cases of non-melanoma skin cancer and 1 meningioma.

Pathogenic or likely pathogenic (P/LP) mutations in 32 genes were reported in 175 CCSs. The prevalence in CCSs (5.8%) was nearly 10-fold higher than in controls (0.6%).

The most commonly mutated genes in CCSs were RB1 (n=43), NF1 (n=22), BRCA2 (n=14), BRCA1 (n=12), and TP53 (n=10).

In a multivariable analysis adjusted for sex, age at primary cancer diagnosis, and treatment, P/LP mutation carriers had a significantly higher rate of any SN (RR=1.8).

The rate of subsequent breast cancer was significantly increased among females with a P/LP mutation (RR= 9.4), recipients of chest radiation (RR=7.9), and those with higher anthracycline exposure (RR=2.4).

The rate of subsequent sarcoma was significantly increased for mutation carriers (RR=10.9) and CCSs with greater exposure to alkylating agents (RR=3.8).

Among irradiated CCSs, P/LP mutations were associated with significantly increased rates of breast cancer (RR=13.9) and sarcoma (RR=10.6)

Among non-irradiated CCSs, P/LP mutations were associated with significantly increased rates of any SN (RR=4.7), breast cancer (RR=7.7), nonmelanoma skin cancer (RR=11.0), and 2 or more histologically distinct SNs (RR=18.6).

The researchers said the higher risk of SNs in CCSs with P/LP mutations suggests all CCSs should be referred for genetic counseling.