Solid organ transplantation contributes significantly to incidence of NHL among children and adolescents

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Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.

Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).

In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).

The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.

“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”

Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.

The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.

“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”

This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.

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Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.

Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).

In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).

The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.

“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”

Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.

The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.

“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”

This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.

 

Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.

Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).

In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).

The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.

“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”

Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.

The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.

“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”

This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.

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Key clinical point: Solid organ transplant recipients contribute a disproportionate fraction of pediatric NHL cases, especially DLBCL cases.

Major finding: Incidence of NHL among the pediatric transplant population was 257 times higher at 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general pediatric population.

Data source: Retrospective cohort study of children and adolescents in the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012.

Disclosures: This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.

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FDA grants priority review of acalabrutinib for second-line treatment of MCL

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The Food and Drug Administration has granted a priority review for acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

The new drug application is based on results from the phase 2 ACE-LY-004 trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory MCL who had received at least one prior therapy.

Results from the trial will be submitted for presentation at a forthcoming medical meeting, makers of the drug AstraZeneca said in a press release announcing the priority review. The company also has a phase 3 trial underway evaluating acalabrutinib as a first-line treatment for patients with MCL.

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The Food and Drug Administration has granted a priority review for acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

The new drug application is based on results from the phase 2 ACE-LY-004 trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory MCL who had received at least one prior therapy.

Results from the trial will be submitted for presentation at a forthcoming medical meeting, makers of the drug AstraZeneca said in a press release announcing the priority review. The company also has a phase 3 trial underway evaluating acalabrutinib as a first-line treatment for patients with MCL.

 

The Food and Drug Administration has granted a priority review for acalabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

The new drug application is based on results from the phase 2 ACE-LY-004 trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory MCL who had received at least one prior therapy.

Results from the trial will be submitted for presentation at a forthcoming medical meeting, makers of the drug AstraZeneca said in a press release announcing the priority review. The company also has a phase 3 trial underway evaluating acalabrutinib as a first-line treatment for patients with MCL.

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Delirium linked to early death in advanced cancer patients

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Delirium linked to early death in advanced cancer patients

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Doctor evaluating patient

A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

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Photo courtesy of the CDC
Doctor evaluating patient

A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

Photo courtesy of the CDC
Doctor evaluating patient

A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

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FDA grants acalabrutinib breakthrough designation

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Mantle cell lymphoma

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.

The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.

Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.

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Mantle cell lymphoma

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.

The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.

Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.

Mantle cell lymphoma

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.

The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.

Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.

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Clinical Endpoints in PTCL: The Road Less Traveled

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Release Date: August 1, 2017
Expiration Date: July 31, 2018

Note: This activity is no longer available for credit.

Agenda

Developing New Strategic Goals in PTCL (duration 27:00)
Andrei R. Shustov, MD
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Seattle, WA, USA

PTCL as a Rare Disease: A Case of Overall Survival (duration 19:00)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY, USA

Why Might Response Rates Differ Between the East and West? (duration 17:00)
Kensei Tobinai, MD, PhD
National Cancer Center Hospital
Tokyo, Japan

Provided by:

Original activity supported by an educational grant from:

Spectrum Pharmaceuticals

Learning Objectives

At the end of the activity, participants should be able to:

  • Explain why progression-free survival is important when treating patients with PTCL
  • Determine when overall survival is possible
  • Describe the challenges of using matched control analysis in PTCL clinical trials
  • Discuss why different response rates to therapy for PTCL may be seen in Asian patients versus North American or European patients and define the possible contributing factors

Target Audience

Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma

Statement of Need

This activity explores clinical endpoints in PTCL, the importance of choosing the appropriate ones and the possibility of achieving them. Global and regional differences in PTCL are also explored as they relate to response rates. The presentations highlight the challenges physicians face in treating PTCL patients and recent developments are discussed to help practitioners evaluate the utility of these endpoints in choosing appropriate treatments to improve outcomes in their patients with PTCL.

 

FACULTY

Faculty

Andrei R. Shustov, MD
Disclosures: Consulting fee: Celgene; BMS

Owen O’Connor, MD, PhD
Disclosures: Consulting fees: Mundipharma; Celgene; Contracted Research: Mundipharma; Spectrum; Celgene; Seattle Genetics; TG Therapeutics; ADCT; Trillium

Kensei Tobinai, MD, PhD
Disclosures: Honoraria: Eisai; HUYA Bioscience International; Janssen; Mundipharma; Takeda; Zenyaku Kogyo; Contracted research: Abbvie; Celgene; Chugai Pharma; Eisai; GlaxoSmithKline; Janssen; Kyowa Hakko Kirin; Mundipharma; Ono Pharmaceutical; SERVIER; Takeda

Permissions

Andrei Shustov presentation

  • Slide 7: PTCL Prognosis Is Indicative of Diverse Biology
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 8: PTCL: Global Epidemiology
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 9: PTCL: USA Epidemiology (top half)
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 9: PTCL: USA Epidemiology (bottom half)
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slide 10: PTCL Prognosis: Histology x Race (USA)
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slide 12: PTCL Prognosis: Clinical Features (top right side)
    • Reprinted with permission. © 2013 American Society of Clinical Oncology. All rights reserved.
  • Slide 14: PTCL Prognosis: Molecular Classifiers (left side)
    • Republished with permission of the American Society of Hematology, from Parilla Castellar ER, et al. Blood 2014;124:1473-1480
  • Slide 14: PTCL Prognosis: Molecular Classifiers (right side)
    • Republished with permission of the American Society of Hematology, from Iqbal J, et al. Blood 2014;123:2915-2923
  • Slide 17: US Epidemiology of PTCL
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slides 18-19: Romidepsin in Relapsed/Refractory PTCL
    • Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.
  • Slides 20-22, 25: Romidepsin in Elderly Patients
    • Shustov A, et al. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma 2017 [Epub ahead of print]. Reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com
  • Slides 27-28: Belinostat in Relapsed/Refractory PTCL
    • Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.

Kensei Tobinai presentation

  • Slide 7: Overall Survival of ATL Pts in JCOG 9801
    • Reprinted with permission. © 2007 American Society of Clinical Oncology. All rights reserved.

Disclaimer

The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

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Release Date: August 1, 2017
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Agenda

Developing New Strategic Goals in PTCL (duration 27:00)
Andrei R. Shustov, MD
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Seattle, WA, USA

PTCL as a Rare Disease: A Case of Overall Survival (duration 19:00)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY, USA

Why Might Response Rates Differ Between the East and West? (duration 17:00)
Kensei Tobinai, MD, PhD
National Cancer Center Hospital
Tokyo, Japan

Provided by:

Original activity supported by an educational grant from:

Spectrum Pharmaceuticals

Learning Objectives

At the end of the activity, participants should be able to:

  • Explain why progression-free survival is important when treating patients with PTCL
  • Determine when overall survival is possible
  • Describe the challenges of using matched control analysis in PTCL clinical trials
  • Discuss why different response rates to therapy for PTCL may be seen in Asian patients versus North American or European patients and define the possible contributing factors

Target Audience

Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma

Statement of Need

This activity explores clinical endpoints in PTCL, the importance of choosing the appropriate ones and the possibility of achieving them. Global and regional differences in PTCL are also explored as they relate to response rates. The presentations highlight the challenges physicians face in treating PTCL patients and recent developments are discussed to help practitioners evaluate the utility of these endpoints in choosing appropriate treatments to improve outcomes in their patients with PTCL.

 

FACULTY

Faculty

Andrei R. Shustov, MD
Disclosures: Consulting fee: Celgene; BMS

Owen O’Connor, MD, PhD
Disclosures: Consulting fees: Mundipharma; Celgene; Contracted Research: Mundipharma; Spectrum; Celgene; Seattle Genetics; TG Therapeutics; ADCT; Trillium

Kensei Tobinai, MD, PhD
Disclosures: Honoraria: Eisai; HUYA Bioscience International; Janssen; Mundipharma; Takeda; Zenyaku Kogyo; Contracted research: Abbvie; Celgene; Chugai Pharma; Eisai; GlaxoSmithKline; Janssen; Kyowa Hakko Kirin; Mundipharma; Ono Pharmaceutical; SERVIER; Takeda

Permissions

Andrei Shustov presentation

  • Slide 7: PTCL Prognosis Is Indicative of Diverse Biology
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 8: PTCL: Global Epidemiology
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 9: PTCL: USA Epidemiology (top half)
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 9: PTCL: USA Epidemiology (bottom half)
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slide 10: PTCL Prognosis: Histology x Race (USA)
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slide 12: PTCL Prognosis: Clinical Features (top right side)
    • Reprinted with permission. © 2013 American Society of Clinical Oncology. All rights reserved.
  • Slide 14: PTCL Prognosis: Molecular Classifiers (left side)
    • Republished with permission of the American Society of Hematology, from Parilla Castellar ER, et al. Blood 2014;124:1473-1480
  • Slide 14: PTCL Prognosis: Molecular Classifiers (right side)
    • Republished with permission of the American Society of Hematology, from Iqbal J, et al. Blood 2014;123:2915-2923
  • Slide 17: US Epidemiology of PTCL
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slides 18-19: Romidepsin in Relapsed/Refractory PTCL
    • Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.
  • Slides 20-22, 25: Romidepsin in Elderly Patients
    • Shustov A, et al. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma 2017 [Epub ahead of print]. Reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com
  • Slides 27-28: Belinostat in Relapsed/Refractory PTCL
    • Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.

Kensei Tobinai presentation

  • Slide 7: Overall Survival of ATL Pts in JCOG 9801
    • Reprinted with permission. © 2007 American Society of Clinical Oncology. All rights reserved.

Disclaimer

The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

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Release Date: August 1, 2017
Expiration Date: July 31, 2018

Note: This activity is no longer available for credit.

Agenda

Developing New Strategic Goals in PTCL (duration 27:00)
Andrei R. Shustov, MD
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Seattle, WA, USA

PTCL as a Rare Disease: A Case of Overall Survival (duration 19:00)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY, USA

Why Might Response Rates Differ Between the East and West? (duration 17:00)
Kensei Tobinai, MD, PhD
National Cancer Center Hospital
Tokyo, Japan

Provided by:

Original activity supported by an educational grant from:

Spectrum Pharmaceuticals

Learning Objectives

At the end of the activity, participants should be able to:

  • Explain why progression-free survival is important when treating patients with PTCL
  • Determine when overall survival is possible
  • Describe the challenges of using matched control analysis in PTCL clinical trials
  • Discuss why different response rates to therapy for PTCL may be seen in Asian patients versus North American or European patients and define the possible contributing factors

Target Audience

Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma

Statement of Need

This activity explores clinical endpoints in PTCL, the importance of choosing the appropriate ones and the possibility of achieving them. Global and regional differences in PTCL are also explored as they relate to response rates. The presentations highlight the challenges physicians face in treating PTCL patients and recent developments are discussed to help practitioners evaluate the utility of these endpoints in choosing appropriate treatments to improve outcomes in their patients with PTCL.

 

FACULTY

Faculty

Andrei R. Shustov, MD
Disclosures: Consulting fee: Celgene; BMS

Owen O’Connor, MD, PhD
Disclosures: Consulting fees: Mundipharma; Celgene; Contracted Research: Mundipharma; Spectrum; Celgene; Seattle Genetics; TG Therapeutics; ADCT; Trillium

Kensei Tobinai, MD, PhD
Disclosures: Honoraria: Eisai; HUYA Bioscience International; Janssen; Mundipharma; Takeda; Zenyaku Kogyo; Contracted research: Abbvie; Celgene; Chugai Pharma; Eisai; GlaxoSmithKline; Janssen; Kyowa Hakko Kirin; Mundipharma; Ono Pharmaceutical; SERVIER; Takeda

Permissions

Andrei Shustov presentation

  • Slide 7: PTCL Prognosis Is Indicative of Diverse Biology
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 8: PTCL: Global Epidemiology
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 9: PTCL: USA Epidemiology (top half)
    • Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved.
  • Slide 9: PTCL: USA Epidemiology (bottom half)
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slide 10: PTCL Prognosis: Histology x Race (USA)
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slide 12: PTCL Prognosis: Clinical Features (top right side)
    • Reprinted with permission. © 2013 American Society of Clinical Oncology. All rights reserved.
  • Slide 14: PTCL Prognosis: Molecular Classifiers (left side)
    • Republished with permission of the American Society of Hematology, from Parilla Castellar ER, et al. Blood 2014;124:1473-1480
  • Slide 14: PTCL Prognosis: Molecular Classifiers (right side)
    • Republished with permission of the American Society of Hematology, from Iqbal J, et al. Blood 2014;123:2915-2923
  • Slide 17: US Epidemiology of PTCL
    • Reprinted with permission. © 2016 American Society of Clinical Oncology. All rights reserved.
  • Slides 18-19: Romidepsin in Relapsed/Refractory PTCL
    • Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.
  • Slides 20-22, 25: Romidepsin in Elderly Patients
    • Shustov A, et al. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma 2017 [Epub ahead of print]. Reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com
  • Slides 27-28: Belinostat in Relapsed/Refractory PTCL
    • Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.

Kensei Tobinai presentation

  • Slide 7: Overall Survival of ATL Pts in JCOG 9801
    • Reprinted with permission. © 2007 American Society of Clinical Oncology. All rights reserved.

Disclaimer

The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

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Evaluation of Fitness, Metabolism, and Quality of Life During Hematopoietic Stem Cell Transplant

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Abstract 30: 2017 AVAHO Meeting

Purpose: The objective of this study is to characterize biochemical and physiologic factors that contribute to changes in patient fitness, body composition, and quality of life (QoL) during hematopoietic stem cell transplantation (HCT).

Background: Though HCT can cure subsets of patients with hematologic malignancies, it carries a high risk of short- and long-term toxicity. Prior work has shown that following both autologous and allogeneic HCT, most patients suffer impairment in QoL for many months after transplant. Efforts to date have inconsistently demonstrated benefit in addressing parameters of nutrition, physical activity, and metabolism.

Methods: This prospective pilot study of 60 patients at VA Puget Sound Marrow Transplant Unit with hematologic malignancy will incorporate multidisciplinary evaluation by endocrinology, nutrition, gastroenterology, and oncology specialties. Assessments before and periodically after HCT include objective measures of fitness by 6-minue walk test, resting energy expenditure, maximum oxygen consumption, handgrip and other muscle group strength, and stair climbing power; body composition by bio-impedance and dual-energy X-ray absorptiometry scans; anabolic and catabolic factors such as insulin growth factor-1, growth hormone, and free and weakly bound testosterone; biochemical markers of inflammatory milieu; and validated questionnaires of nutrition, functional status, and QoL.

Results: The protocol opened to accrual in March 2017. To date, 12 patients have enrolled in study, and posttransplant evaluations (approximately 30 days after transplantation, median = 36) have been performed on 4. Early findings suggest relatively preserved body weight and composition but trends toward decreased QoL and fitness, particularly in aerobic capacity, handgrip strength, and total lower body fitness. Updated findings will be presented at the Association of VA Hematology/Oncology Conference.

Implications: With improving survival outcomes following HCT for hematologic malignancies due to advances in therapeutics and supportive care, increased attention will be directed at optimizing patient-centered quality outcomes. Understanding of the biochemical and physiologic factors underlying these outcomes may lead to refinements in prognostic models and present targets for risk mitigation interventions in the peri-transplant period.

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Abstract 30: 2017 AVAHO Meeting
Abstract 30: 2017 AVAHO Meeting

Purpose: The objective of this study is to characterize biochemical and physiologic factors that contribute to changes in patient fitness, body composition, and quality of life (QoL) during hematopoietic stem cell transplantation (HCT).

Background: Though HCT can cure subsets of patients with hematologic malignancies, it carries a high risk of short- and long-term toxicity. Prior work has shown that following both autologous and allogeneic HCT, most patients suffer impairment in QoL for many months after transplant. Efforts to date have inconsistently demonstrated benefit in addressing parameters of nutrition, physical activity, and metabolism.

Methods: This prospective pilot study of 60 patients at VA Puget Sound Marrow Transplant Unit with hematologic malignancy will incorporate multidisciplinary evaluation by endocrinology, nutrition, gastroenterology, and oncology specialties. Assessments before and periodically after HCT include objective measures of fitness by 6-minue walk test, resting energy expenditure, maximum oxygen consumption, handgrip and other muscle group strength, and stair climbing power; body composition by bio-impedance and dual-energy X-ray absorptiometry scans; anabolic and catabolic factors such as insulin growth factor-1, growth hormone, and free and weakly bound testosterone; biochemical markers of inflammatory milieu; and validated questionnaires of nutrition, functional status, and QoL.

Results: The protocol opened to accrual in March 2017. To date, 12 patients have enrolled in study, and posttransplant evaluations (approximately 30 days after transplantation, median = 36) have been performed on 4. Early findings suggest relatively preserved body weight and composition but trends toward decreased QoL and fitness, particularly in aerobic capacity, handgrip strength, and total lower body fitness. Updated findings will be presented at the Association of VA Hematology/Oncology Conference.

Implications: With improving survival outcomes following HCT for hematologic malignancies due to advances in therapeutics and supportive care, increased attention will be directed at optimizing patient-centered quality outcomes. Understanding of the biochemical and physiologic factors underlying these outcomes may lead to refinements in prognostic models and present targets for risk mitigation interventions in the peri-transplant period.

Purpose: The objective of this study is to characterize biochemical and physiologic factors that contribute to changes in patient fitness, body composition, and quality of life (QoL) during hematopoietic stem cell transplantation (HCT).

Background: Though HCT can cure subsets of patients with hematologic malignancies, it carries a high risk of short- and long-term toxicity. Prior work has shown that following both autologous and allogeneic HCT, most patients suffer impairment in QoL for many months after transplant. Efforts to date have inconsistently demonstrated benefit in addressing parameters of nutrition, physical activity, and metabolism.

Methods: This prospective pilot study of 60 patients at VA Puget Sound Marrow Transplant Unit with hematologic malignancy will incorporate multidisciplinary evaluation by endocrinology, nutrition, gastroenterology, and oncology specialties. Assessments before and periodically after HCT include objective measures of fitness by 6-minue walk test, resting energy expenditure, maximum oxygen consumption, handgrip and other muscle group strength, and stair climbing power; body composition by bio-impedance and dual-energy X-ray absorptiometry scans; anabolic and catabolic factors such as insulin growth factor-1, growth hormone, and free and weakly bound testosterone; biochemical markers of inflammatory milieu; and validated questionnaires of nutrition, functional status, and QoL.

Results: The protocol opened to accrual in March 2017. To date, 12 patients have enrolled in study, and posttransplant evaluations (approximately 30 days after transplantation, median = 36) have been performed on 4. Early findings suggest relatively preserved body weight and composition but trends toward decreased QoL and fitness, particularly in aerobic capacity, handgrip strength, and total lower body fitness. Updated findings will be presented at the Association of VA Hematology/Oncology Conference.

Implications: With improving survival outcomes following HCT for hematologic malignancies due to advances in therapeutics and supportive care, increased attention will be directed at optimizing patient-centered quality outcomes. Understanding of the biochemical and physiologic factors underlying these outcomes may lead to refinements in prognostic models and present targets for risk mitigation interventions in the peri-transplant period.

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CK2 Correlates With Overall and Progression-Free Survival in Oropharyngeal Squamous Cell Carcinoma

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Changed
Fri, 09/08/2017 - 13:53
Abstract 22: 2017 AVAHO Meeting

Purpose: The purpose of this study is to determine whether CK2 expression may be a biomarker for clinical outcomes in advanced oropharyngeal squamous cell carcinoma.

Background: Elevated protein kinase CK2 protein and activity has correlated with poor clinical outcome in patients with various cancers. CK2 is a serine/threonine kinase that has a broad range of intracellular roles that include regulation of apoptosis and DNA repair. However, the prognostic or predictive value of CK2 has not been studied in HPV-related oropharyngeal squamous cell carcinoma (OPSCC).

Methods: A retrospective cohort study of patients diagnosed with OPSCC from 2005-2015 in the Minneapolis Veterans Affairs Healthcare System was performed. Patient demographic, treatment, and clinical outcome data were collected. Archived tumor tissue blocks were stained for p16 (surrogate for HPV-positivity) and CK2α via immunohistochemistry (IHC). The CK2α IHC stain was scored by two staff pathologists with an ordinal scale of 1 (weak) to 3 (strong).

Data Analysis: X2 test of independence, with the 0.01 level considered significant for observed differences

Results: A total of 116 patients were identified that met inclusion criteria. IHC staining for p16 was positive in 80/116 (69%) patients and negative in 36/116 (31%) patients. Overall survival (OS) and progression-free survival (PFS) at 4 years postdiagnosis for p16-positive tumors (p16+) was 71% and 64%, respectively, while the OS and PFS at 4 years for p16-negative tumors was 36% and 32%, respectively. For CK2 IHC scores 1, 2, and 3, respectively, the OS at 4 years was 31%, 75%, and 65%, respectively, while the PFS for scores 1, 2, and 3 at four years was 32%, 65%, and 53%, respectively. In the CK2 IHC score groups, 1, 2, and 3, respectively, p16 positivity vs. negativity was 26% vs. 74%, 79% vs. 21%, and 89% vs. 11%, respectively.

Implications: High CK2 abundance is associated with higher PFS and OS at 4 years in patients with p16+ OPSCC. Further study is needed better define the relationship between p16 expression and CK2 expression in OPSCC.

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S22-S23
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Abstract 22: 2017 AVAHO Meeting
Abstract 22: 2017 AVAHO Meeting

Purpose: The purpose of this study is to determine whether CK2 expression may be a biomarker for clinical outcomes in advanced oropharyngeal squamous cell carcinoma.

Background: Elevated protein kinase CK2 protein and activity has correlated with poor clinical outcome in patients with various cancers. CK2 is a serine/threonine kinase that has a broad range of intracellular roles that include regulation of apoptosis and DNA repair. However, the prognostic or predictive value of CK2 has not been studied in HPV-related oropharyngeal squamous cell carcinoma (OPSCC).

Methods: A retrospective cohort study of patients diagnosed with OPSCC from 2005-2015 in the Minneapolis Veterans Affairs Healthcare System was performed. Patient demographic, treatment, and clinical outcome data were collected. Archived tumor tissue blocks were stained for p16 (surrogate for HPV-positivity) and CK2α via immunohistochemistry (IHC). The CK2α IHC stain was scored by two staff pathologists with an ordinal scale of 1 (weak) to 3 (strong).

Data Analysis: X2 test of independence, with the 0.01 level considered significant for observed differences

Results: A total of 116 patients were identified that met inclusion criteria. IHC staining for p16 was positive in 80/116 (69%) patients and negative in 36/116 (31%) patients. Overall survival (OS) and progression-free survival (PFS) at 4 years postdiagnosis for p16-positive tumors (p16+) was 71% and 64%, respectively, while the OS and PFS at 4 years for p16-negative tumors was 36% and 32%, respectively. For CK2 IHC scores 1, 2, and 3, respectively, the OS at 4 years was 31%, 75%, and 65%, respectively, while the PFS for scores 1, 2, and 3 at four years was 32%, 65%, and 53%, respectively. In the CK2 IHC score groups, 1, 2, and 3, respectively, p16 positivity vs. negativity was 26% vs. 74%, 79% vs. 21%, and 89% vs. 11%, respectively.

Implications: High CK2 abundance is associated with higher PFS and OS at 4 years in patients with p16+ OPSCC. Further study is needed better define the relationship between p16 expression and CK2 expression in OPSCC.

Purpose: The purpose of this study is to determine whether CK2 expression may be a biomarker for clinical outcomes in advanced oropharyngeal squamous cell carcinoma.

Background: Elevated protein kinase CK2 protein and activity has correlated with poor clinical outcome in patients with various cancers. CK2 is a serine/threonine kinase that has a broad range of intracellular roles that include regulation of apoptosis and DNA repair. However, the prognostic or predictive value of CK2 has not been studied in HPV-related oropharyngeal squamous cell carcinoma (OPSCC).

Methods: A retrospective cohort study of patients diagnosed with OPSCC from 2005-2015 in the Minneapolis Veterans Affairs Healthcare System was performed. Patient demographic, treatment, and clinical outcome data were collected. Archived tumor tissue blocks were stained for p16 (surrogate for HPV-positivity) and CK2α via immunohistochemistry (IHC). The CK2α IHC stain was scored by two staff pathologists with an ordinal scale of 1 (weak) to 3 (strong).

Data Analysis: X2 test of independence, with the 0.01 level considered significant for observed differences

Results: A total of 116 patients were identified that met inclusion criteria. IHC staining for p16 was positive in 80/116 (69%) patients and negative in 36/116 (31%) patients. Overall survival (OS) and progression-free survival (PFS) at 4 years postdiagnosis for p16-positive tumors (p16+) was 71% and 64%, respectively, while the OS and PFS at 4 years for p16-negative tumors was 36% and 32%, respectively. For CK2 IHC scores 1, 2, and 3, respectively, the OS at 4 years was 31%, 75%, and 65%, respectively, while the PFS for scores 1, 2, and 3 at four years was 32%, 65%, and 53%, respectively. In the CK2 IHC score groups, 1, 2, and 3, respectively, p16 positivity vs. negativity was 26% vs. 74%, 79% vs. 21%, and 89% vs. 11%, respectively.

Implications: High CK2 abundance is associated with higher PFS and OS at 4 years in patients with p16+ OPSCC. Further study is needed better define the relationship between p16 expression and CK2 expression in OPSCC.

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Understanding childhood cancer in sub-Saharan Africa

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Understanding childhood cancer in sub-Saharan Africa

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Children in The Gambia

Researchers say they have published the most extensive data ever collected on childhood cancer in sub-Saharan Africa.

On the African continent, only South Africa operates a childhood cancer registry on the national level.

Researchers brought together data from 16 of the smaller, local registries, collecting this information for the first time and presenting it in an accessible format.

The data were published in ecancermedicalscience.

Examining the data in context allowed the researchers to notice trends in cancer incidence. For example, they found that, in Blantyre, Malawi’s second-largest city, the cumulative risk of a child developing Burkitt lymphoma is 2 in every thousand.

The researchers called this incidence “remarkable” and noted that the global research community is largely unaware of this.

“Everything starts with awareness,” said study author Cristina Stefan, global clinical leader of oncology for Roche Diagnostics International Ltd of Switzerland and director of the African Medical Research and Innovation Institute.

“It is highly necessary to publicize these data, which, at the moment, represent the best image of the malignant disease in children in the respective regions.”

The researchers also noted that factors such as the prevalence of malaria and the Epstein-Barr virus contribute to the unique epidemiology of childhood cancer in Africa.

“Our colleagues can learn that the patterns and distribution of cancers in Africa are totally different from Europe, and there is a need for further research into the roles of factors such as genetic predispositions and the influence of infections and other comorbidities in the evolution of cancer,” Dr Stefan said.

“We have learned many universal lessons about data collection as we prepared this work. Our hope is that the publication of this monograph will open the forums for future discussions and that the work will be referenced for the better understanding of cancer in children in Africa and used to improve outcomes for children affected there.”

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Photo by Aurimas Rimsa
Children in The Gambia

Researchers say they have published the most extensive data ever collected on childhood cancer in sub-Saharan Africa.

On the African continent, only South Africa operates a childhood cancer registry on the national level.

Researchers brought together data from 16 of the smaller, local registries, collecting this information for the first time and presenting it in an accessible format.

The data were published in ecancermedicalscience.

Examining the data in context allowed the researchers to notice trends in cancer incidence. For example, they found that, in Blantyre, Malawi’s second-largest city, the cumulative risk of a child developing Burkitt lymphoma is 2 in every thousand.

The researchers called this incidence “remarkable” and noted that the global research community is largely unaware of this.

“Everything starts with awareness,” said study author Cristina Stefan, global clinical leader of oncology for Roche Diagnostics International Ltd of Switzerland and director of the African Medical Research and Innovation Institute.

“It is highly necessary to publicize these data, which, at the moment, represent the best image of the malignant disease in children in the respective regions.”

The researchers also noted that factors such as the prevalence of malaria and the Epstein-Barr virus contribute to the unique epidemiology of childhood cancer in Africa.

“Our colleagues can learn that the patterns and distribution of cancers in Africa are totally different from Europe, and there is a need for further research into the roles of factors such as genetic predispositions and the influence of infections and other comorbidities in the evolution of cancer,” Dr Stefan said.

“We have learned many universal lessons about data collection as we prepared this work. Our hope is that the publication of this monograph will open the forums for future discussions and that the work will be referenced for the better understanding of cancer in children in Africa and used to improve outcomes for children affected there.”

Photo by Aurimas Rimsa
Children in The Gambia

Researchers say they have published the most extensive data ever collected on childhood cancer in sub-Saharan Africa.

On the African continent, only South Africa operates a childhood cancer registry on the national level.

Researchers brought together data from 16 of the smaller, local registries, collecting this information for the first time and presenting it in an accessible format.

The data were published in ecancermedicalscience.

Examining the data in context allowed the researchers to notice trends in cancer incidence. For example, they found that, in Blantyre, Malawi’s second-largest city, the cumulative risk of a child developing Burkitt lymphoma is 2 in every thousand.

The researchers called this incidence “remarkable” and noted that the global research community is largely unaware of this.

“Everything starts with awareness,” said study author Cristina Stefan, global clinical leader of oncology for Roche Diagnostics International Ltd of Switzerland and director of the African Medical Research and Innovation Institute.

“It is highly necessary to publicize these data, which, at the moment, represent the best image of the malignant disease in children in the respective regions.”

The researchers also noted that factors such as the prevalence of malaria and the Epstein-Barr virus contribute to the unique epidemiology of childhood cancer in Africa.

“Our colleagues can learn that the patterns and distribution of cancers in Africa are totally different from Europe, and there is a need for further research into the roles of factors such as genetic predispositions and the influence of infections and other comorbidities in the evolution of cancer,” Dr Stefan said.

“We have learned many universal lessons about data collection as we prepared this work. Our hope is that the publication of this monograph will open the forums for future discussions and that the work will be referenced for the better understanding of cancer in children in Africa and used to improve outcomes for children affected there.”

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ASCO updates guidelines on antiemetic use in cancer patients

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Cancer patient receiving chemotherapy

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.

The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.

“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.

“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”

To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.

“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.

“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”

Key recommendations in the updated guidelines include:

For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.

For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).

Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.

Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.

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Photo by Rhoda Baer
Cancer patient receiving chemotherapy

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.

The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.

“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.

“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”

To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.

“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.

“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”

Key recommendations in the updated guidelines include:

For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.

For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).

Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.

Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.

Photo by Rhoda Baer
Cancer patient receiving chemotherapy

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.

The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.

“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.

“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”

To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.

“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.

“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”

Key recommendations in the updated guidelines include:

For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.

For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).

Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.

Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.

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Developing better mouse models

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Fri, 07/28/2017 - 00:03
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Developing better mouse models

Photo by Aaron Logan
Lab mice

Researchers say they have developed a new approach to model human immune variation that overcomes the limitations of traditional mouse models.

With this approach, the team identified genetic markers that directly correlate with the outcome of inflammatory and malignant diseases in humans, including chronic lymphocytic leukemia and Burkitt lymphoma.

The findings suggest that accounting for immune diversity is critical to the success of predicting disease outcomes based on immune cell measurements.

The team reported these findings in Nature Communications.

Traditionally, researchers have relied on inbred mouse strains to gain insight into human diseases while reducing experimental noise.

“If you take a black, a brown, or a white mouse, each one will give you a different answer in the same assay,” said Klaus Ley, MD, of La Jolla Institute for Allergy and Immunology in California.

“For example, if you vaccinate them, their responses will be different, which creates a lot of experimental noise. However, when you think about patients, or even healthy people, we are all different.”

To mine those differences for information, the researchers embraced the experimental noise. Instead of analyzing a single inbred mouse strain, they turned to the hybrid mouse diversity panel (HDMP).

The HDMP is a panel of about 100 different inbred mouse strains that mirror the breadth of genetic and immunological diversity found in the human population.

The researchers studied the natural variation in the activation pattern of abdominal macrophages. Macrophages isolated from 83 different mouse strains from the HDMP were exposed to lipopolysaccharide (LPS), a major component of the outer wall of gram-negative bacteria.

“Fundamentally, when the immune system is confronted with gram-negative bacteria, it can deal with the situation in 2 ways—either it gets very angry and tries to kill the bacteria or it can wall them off in an attempt to live with it,” explained Dr Ley. “Both strategies carry a certain risk, but a long evolutionary history has ensured that mice and people can survive with either strategy.”

The LPS-induced reactions of the macrophages covered the whole spectrum—from very aggressive (LPS+) to very tolerant (LPS-), depending on the mouse strain.

Next, the researchers asked which genes were active during each type of response to identify gene signatures that correlated with LPS responsiveness.

The team then ran these gene signatures across various human gene expression data sets and discovered they strongly correlated with human disease outcomes.

For example, macrophages isolated from healthy joints were enriched in LPS-tolerant genes, whereas macrophages from rheumatoid arthritis patients were strongly skewed toward LPS-aggressive.

Since it was known that mice and people with the aggressive phenotype are better at fighting cancer, the researchers specifically asked whether the level of LPS responsiveness could predict tumor survival.

After analyzing data from 18,000 biopsies across 39 different tumor types, the team found the LPS+ gene signature strongly correlated with survival, while the LPS- signature correlated with cancer death.

The pattern was significant across many types of cancer, including chronic lymphocytic leukemia, Burkitt lymphoma, osteosarcoma, melanoma, and large-cell lung carcinoma.

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Photo by Aaron Logan
Lab mice

Researchers say they have developed a new approach to model human immune variation that overcomes the limitations of traditional mouse models.

With this approach, the team identified genetic markers that directly correlate with the outcome of inflammatory and malignant diseases in humans, including chronic lymphocytic leukemia and Burkitt lymphoma.

The findings suggest that accounting for immune diversity is critical to the success of predicting disease outcomes based on immune cell measurements.

The team reported these findings in Nature Communications.

Traditionally, researchers have relied on inbred mouse strains to gain insight into human diseases while reducing experimental noise.

“If you take a black, a brown, or a white mouse, each one will give you a different answer in the same assay,” said Klaus Ley, MD, of La Jolla Institute for Allergy and Immunology in California.

“For example, if you vaccinate them, their responses will be different, which creates a lot of experimental noise. However, when you think about patients, or even healthy people, we are all different.”

To mine those differences for information, the researchers embraced the experimental noise. Instead of analyzing a single inbred mouse strain, they turned to the hybrid mouse diversity panel (HDMP).

The HDMP is a panel of about 100 different inbred mouse strains that mirror the breadth of genetic and immunological diversity found in the human population.

The researchers studied the natural variation in the activation pattern of abdominal macrophages. Macrophages isolated from 83 different mouse strains from the HDMP were exposed to lipopolysaccharide (LPS), a major component of the outer wall of gram-negative bacteria.

“Fundamentally, when the immune system is confronted with gram-negative bacteria, it can deal with the situation in 2 ways—either it gets very angry and tries to kill the bacteria or it can wall them off in an attempt to live with it,” explained Dr Ley. “Both strategies carry a certain risk, but a long evolutionary history has ensured that mice and people can survive with either strategy.”

The LPS-induced reactions of the macrophages covered the whole spectrum—from very aggressive (LPS+) to very tolerant (LPS-), depending on the mouse strain.

Next, the researchers asked which genes were active during each type of response to identify gene signatures that correlated with LPS responsiveness.

The team then ran these gene signatures across various human gene expression data sets and discovered they strongly correlated with human disease outcomes.

For example, macrophages isolated from healthy joints were enriched in LPS-tolerant genes, whereas macrophages from rheumatoid arthritis patients were strongly skewed toward LPS-aggressive.

Since it was known that mice and people with the aggressive phenotype are better at fighting cancer, the researchers specifically asked whether the level of LPS responsiveness could predict tumor survival.

After analyzing data from 18,000 biopsies across 39 different tumor types, the team found the LPS+ gene signature strongly correlated with survival, while the LPS- signature correlated with cancer death.

The pattern was significant across many types of cancer, including chronic lymphocytic leukemia, Burkitt lymphoma, osteosarcoma, melanoma, and large-cell lung carcinoma.

Photo by Aaron Logan
Lab mice

Researchers say they have developed a new approach to model human immune variation that overcomes the limitations of traditional mouse models.

With this approach, the team identified genetic markers that directly correlate with the outcome of inflammatory and malignant diseases in humans, including chronic lymphocytic leukemia and Burkitt lymphoma.

The findings suggest that accounting for immune diversity is critical to the success of predicting disease outcomes based on immune cell measurements.

The team reported these findings in Nature Communications.

Traditionally, researchers have relied on inbred mouse strains to gain insight into human diseases while reducing experimental noise.

“If you take a black, a brown, or a white mouse, each one will give you a different answer in the same assay,” said Klaus Ley, MD, of La Jolla Institute for Allergy and Immunology in California.

“For example, if you vaccinate them, their responses will be different, which creates a lot of experimental noise. However, when you think about patients, or even healthy people, we are all different.”

To mine those differences for information, the researchers embraced the experimental noise. Instead of analyzing a single inbred mouse strain, they turned to the hybrid mouse diversity panel (HDMP).

The HDMP is a panel of about 100 different inbred mouse strains that mirror the breadth of genetic and immunological diversity found in the human population.

The researchers studied the natural variation in the activation pattern of abdominal macrophages. Macrophages isolated from 83 different mouse strains from the HDMP were exposed to lipopolysaccharide (LPS), a major component of the outer wall of gram-negative bacteria.

“Fundamentally, when the immune system is confronted with gram-negative bacteria, it can deal with the situation in 2 ways—either it gets very angry and tries to kill the bacteria or it can wall them off in an attempt to live with it,” explained Dr Ley. “Both strategies carry a certain risk, but a long evolutionary history has ensured that mice and people can survive with either strategy.”

The LPS-induced reactions of the macrophages covered the whole spectrum—from very aggressive (LPS+) to very tolerant (LPS-), depending on the mouse strain.

Next, the researchers asked which genes were active during each type of response to identify gene signatures that correlated with LPS responsiveness.

The team then ran these gene signatures across various human gene expression data sets and discovered they strongly correlated with human disease outcomes.

For example, macrophages isolated from healthy joints were enriched in LPS-tolerant genes, whereas macrophages from rheumatoid arthritis patients were strongly skewed toward LPS-aggressive.

Since it was known that mice and people with the aggressive phenotype are better at fighting cancer, the researchers specifically asked whether the level of LPS responsiveness could predict tumor survival.

After analyzing data from 18,000 biopsies across 39 different tumor types, the team found the LPS+ gene signature strongly correlated with survival, while the LPS- signature correlated with cancer death.

The pattern was significant across many types of cancer, including chronic lymphocytic leukemia, Burkitt lymphoma, osteosarcoma, melanoma, and large-cell lung carcinoma.

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