After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).

“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”

The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.

In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.

However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.

In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).

“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.

“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.

Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.

Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).

“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”

The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.

After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).

“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”

The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.

In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.

However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.

In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).

“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.

“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.

Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.

Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).

“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”

The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.

After older patients undergo lung resection for stage I non–small-cell lung cancer, they are actually at greater risk of death from something other than lung cancer for up to 2.5 years, according to researchers at Memorial Sloan Kettering Cancer Center, New York. The findings were published online in the Journal of Clinical Oncology (2016;34: doi: 10.1200/JCO.2016.69.0834).

“As age increases, the risk of competing events increases, such as death from noncancer diseases,” wrote Takashi Eguchi, MD, and coauthors. “In this era of personalized cancer therapy, important to the stratification of individualized treatments is the determination of how both cancer and noncancer risk factors – specifically, comorbidities associated with increasing age – contribute to the risk of death.”

The researchers examined outcomes in three different age groups: younger than 65, 65-74, and 75 and older. The study focused on 2,186 patients with pathologic stage I non–small-cell lung cancer (NSCLC) among a population of 5,371 consecutive patients who had resection for primary lung cancer from 2000 to 2011. Seventy percent of patients in the study group were 65 and older, and 29.2% were 75 and older.

In all age groups, the calculated 5-year cumulative incidence of death (CID) for lung cancer–specific causes exceeded that for noncancer causes, but at significant intervals the 65-and-over groups were more likely to die from the latter. For the overall study group, noncancer-specific causes accounted for a higher CID through 18 months after surgery, when the CID for both cancer and noncancer causes crossed at around 2.9. At 5 years, the overall lung cancer–specific CID was 10.4 vs. 5.3 for noncancer specific causes.

However, in the older age groups, those trends were more pronounced. In those aged 65-74, CID for both causes met at around 3.15 at 18 months (10.7 for lung cancer–specific and 4.9 for noncancer specific at 5 years), whereas for those 75 and older, CID for noncancer causes exceeded that for lung cancer–related causes for 2.5 years, when both were around 6; reaching 13.2 for lung cancer–specific and 9 for noncancer-specific at 5 years.

In the 65-and-younger group, lung cancer– and noncancer-specific CIDs were equal for about 3 months after surgery, when the lung cancer deaths tracked upward and the trends diverged (at 5 years, CID was 7.5 for lung cancer–specific and 1 for noncancer specific).

“We have shown that in patients with stage I NSCLC, the majority of postoperative severe morbidity, 1-year mortality, and 5-year noncancer-specific mortality were attributable to cardiorespiratory diseases,” Dr. Eguchi and colleagues said.

“We have also shown that short-term mortality is primarily attributable to noncancer-specific diseases.” The findings underscore the importance of screening older patients for noncancer-specific diseases that could alter outcomes, the researchers said.

Of the 2,186 stage I NSCLC patients in the study, 167 developed severe morbidities after surgery; 68.3% developed respiratory problems and 18.6% went on to develop cardiovascular problems. Patients who had lobectomy were more likely to develop respiratory problems than were those who had sublobar resection, Dr. Eguchi and coauthors said.

Respiratory and cardiovascular diseases were the most frequent causes of death early after surgery. At 30 days, respiratory disease accounted for 5 deaths and cardiovascular disease 7 of 15 total deaths at 30 days; and at 90 days, 11 and 7, respectively, of 27 overall deaths. Even at 1 year, noncancer issues were the leading cause of death (50%), followed by lung cancer–specific causes (27.8%) and other cancer specific disease (13.3%).

“Noncancer-specific mortality represents a significant competing event for lung cancer–specific mortality, with an increasing impact as age increases,” Dr. Eguchi and coauthors said. “These findings can provide patients with more accurate information on survivorship on the basis of their individual preoperative status and help determine patients’ optimal treatment options.”

The study received financial support from coauthor Prasad S. Adusumilli, MD. Dr. Eguchi and Dr. Adusumilli and the other coauthors had no relevant financial disclosures.

Young children and infants who require cardiac valve replacement are limited to fixed-diameter prostheses that cannot accommodate their growth, but researchers at Boston Children’s Hospital have reinforced an expandable bovine jugular vein graft using an external stent and implanted it in 42 patients with acceptable short-term results, according to a report in the Journal of Thoracic and Cardiovascular Surgery.

In 4 years, the modified Melody valve (Medtronic) has proved amenable to enlargement via catheterization as the child grows, Sitaram M. Emani, MD, and coauthors said. “The valve was competent with low gradient acutely postoperatively in all patients,” Dr. Emani and his coauthors said (J Thorac Cardiovasc Surg. 2016 Dec;152[6]:1514-23).

Young children and infants who require cardiac valve replacement are limited to fixed-diameter prostheses that cannot accommodate their growth, but researchers at Boston Children’s Hospital have reinforced an expandable bovine jugular vein graft using an external stent and implanted it in 42 patients with acceptable short-term results, according to a report in the Journal of Thoracic and Cardiovascular Surgery.

In 4 years, the modified Melody valve (Medtronic) has proved amenable to enlargement via catheterization as the child grows, Sitaram M. Emani, MD, and coauthors said. “The valve was competent with low gradient acutely postoperatively in all patients,” Dr. Emani and his coauthors said (J Thorac Cardiovasc Surg. 2016 Dec;152[6]:1514-23).

Young children and infants who require cardiac valve replacement are limited to fixed-diameter prostheses that cannot accommodate their growth, but researchers at Boston Children’s Hospital have reinforced an expandable bovine jugular vein graft using an external stent and implanted it in 42 patients with acceptable short-term results, according to a report in the Journal of Thoracic and Cardiovascular Surgery.

In 4 years, the modified Melody valve (Medtronic) has proved amenable to enlargement via catheterization as the child grows, Sitaram M. Emani, MD, and coauthors said. “The valve was competent with low gradient acutely postoperatively in all patients,” Dr. Emani and his coauthors said (J Thorac Cardiovasc Surg. 2016 Dec;152[6]:1514-23).

At the recent Launch Pad: Pathways to Cancer Innovation, November 29, 2016, Federal Practitioner sat down for an exclusive interview with VA Under Secretary of Health David J. Shulkin, MD.  The below video that discusses ongoing efforts to improve coordination of care with community providers, the VA’s commitment to expanding the scope of practice for advanced practice registered nurses (APRNs), and the recruitment challenges for filling more than 46,000 health care vacancies. Dr. Shulkin also discussed VA progress over the past 18 months.

At the recent Launch Pad: Pathways to Cancer Innovation, November 29, 2016, Federal Practitioner sat down for an exclusive interview with VA Under Secretary of Health David J. Shulkin, MD.  The below video that discusses ongoing efforts to improve coordination of care with community providers, the VA’s commitment to expanding the scope of practice for advanced practice registered nurses (APRNs), and the recruitment challenges for filling more than 46,000 health care vacancies. Dr. Shulkin also discussed VA progress over the past 18 months.

At the recent Launch Pad: Pathways to Cancer Innovation, November 29, 2016, Federal Practitioner sat down for an exclusive interview with VA Under Secretary of Health David J. Shulkin, MD.  The below video that discusses ongoing efforts to improve coordination of care with community providers, the VA’s commitment to expanding the scope of practice for advanced practice registered nurses (APRNs), and the recruitment challenges for filling more than 46,000 health care vacancies. Dr. Shulkin also discussed VA progress over the past 18 months.

Low-dose aspirin is recommended to help prevent colorectal cancer and vascular disease as well as to reduce mortality. Research suggests that low-dose aspirin also can be useful as an adjunct treatment in established cancers. The potential, however, is offset by concerns about bleeding.

Are the concerns valid? When gauging the risks vs benefits of aspirin for patients at risk for bleeding, considering not only the severity of events, but also the frequency is important, say researchers from Cardiff University, Hywel Dda University, University of Cambridge, Harvard, University of Zaragoza, University of South Wales, Swansea University, National University of Singapore, and University of Leicester.

Related: A Better Way to Predict Colorectal Cancer Relapse?

 They point out that most estimates of harm from aspirin are based on the frequency of “major” gastrointestinal (GI) bleeding together with cerebral bleeding. But they also note that although GI bleeds can be severe, they’re “acute events usually followed by recovery without sequelae.” Strokes, on the other hand, can have lasting effects in survivors; and people who survive heart attacks or cancer may require complex and lifelong interventions.

The researchers suggest weighing the risk of fatal bleeds attributable to aspirin with the severity of the disease events prevented. And the distinction between GI bleeding and fatal bleeding isn’t trivial, they contend. Studies have already shown that the risk of death from aspirin-related GI bleeds is lower than that of spontaneous GI bleeding.

To put the discussion on a more even footing, the research team looked at 11 long-term, randomized controlled trials of aspirin prophylaxis with data on fatal adverse effects (AEs). They also incorporated new data from direct e-mail contact with the authors of some of the studies.

They found that although aspirin increases the risk of GI bleeding by about 60%, low-dose aspirin is associated with a lower risk of fatality among the patients who develop GI bleeding. The researchers note that no report mentioned the use of gastric protection by proton pump inhibitor or other treatment.

Most important, the researchers say, is the finding that among all the subjects who were taking aspirin, there was no increase in death from GI bleeding compared with those randomized to take no aspirin.

Related: Colorectal Screening: Available but Underused

Also important, they add, is to bear in mind the duration of aspirin taking. Almost all studies of cancer prevention, they note, show a 3- to 5-year delay before the benefits of aspirin are clinically apparent (because the effects on cells take a while to show up, that is, as the absence of a tumor).

However, the incidence of GI bleeding attributable to aspirin seems to drop over time: Within the first month of aspirin taking, the risk increases more than 4-fold, but then declines rapidly. After about 3 to 5 years of taking aspirin, there seems to be no excess in GI bleeds. Similarly, most deaths from bleeding happen with the first month, implying underlying untreated gastric pathology, the researchers say.

GI bleeds are still the majority of the AEs caused by aspirin, but thanks to better treatments, GI bleeding and fatal bleeding have declined as much as 20% to 50% in some countries, such as Scotland, Spain, U.S., and Wales. In the risk-benefit analysis, however, the researchers say, the “undesirable effect” of prophylactic aspirin as serious as a vascular event or cancer is rare: Low-dose aspirin is associated with 1 death and 1 disabling hemorrhagic stroke per year in every 10,000 people, and that number could be lower if hypertension is treated adequately.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Source:
Elwood PC, Morgan G, Galante J, et al. PLoS One. 2016;11(11): e0166166.
doi: 10.1371/journal.pone.0166166.

Low-dose aspirin is recommended to help prevent colorectal cancer and vascular disease as well as to reduce mortality. Research suggests that low-dose aspirin also can be useful as an adjunct treatment in established cancers. The potential, however, is offset by concerns about bleeding.

Are the concerns valid? When gauging the risks vs benefits of aspirin for patients at risk for bleeding, considering not only the severity of events, but also the frequency is important, say researchers from Cardiff University, Hywel Dda University, University of Cambridge, Harvard, University of Zaragoza, University of South Wales, Swansea University, National University of Singapore, and University of Leicester.

Related: A Better Way to Predict Colorectal Cancer Relapse?

 They point out that most estimates of harm from aspirin are based on the frequency of “major” gastrointestinal (GI) bleeding together with cerebral bleeding. But they also note that although GI bleeds can be severe, they’re “acute events usually followed by recovery without sequelae.” Strokes, on the other hand, can have lasting effects in survivors; and people who survive heart attacks or cancer may require complex and lifelong interventions.

The researchers suggest weighing the risk of fatal bleeds attributable to aspirin with the severity of the disease events prevented. And the distinction between GI bleeding and fatal bleeding isn’t trivial, they contend. Studies have already shown that the risk of death from aspirin-related GI bleeds is lower than that of spontaneous GI bleeding.

To put the discussion on a more even footing, the research team looked at 11 long-term, randomized controlled trials of aspirin prophylaxis with data on fatal adverse effects (AEs). They also incorporated new data from direct e-mail contact with the authors of some of the studies.

They found that although aspirin increases the risk of GI bleeding by about 60%, low-dose aspirin is associated with a lower risk of fatality among the patients who develop GI bleeding. The researchers note that no report mentioned the use of gastric protection by proton pump inhibitor or other treatment.

Most important, the researchers say, is the finding that among all the subjects who were taking aspirin, there was no increase in death from GI bleeding compared with those randomized to take no aspirin.

Related: Colorectal Screening: Available but Underused

Also important, they add, is to bear in mind the duration of aspirin taking. Almost all studies of cancer prevention, they note, show a 3- to 5-year delay before the benefits of aspirin are clinically apparent (because the effects on cells take a while to show up, that is, as the absence of a tumor).

However, the incidence of GI bleeding attributable to aspirin seems to drop over time: Within the first month of aspirin taking, the risk increases more than 4-fold, but then declines rapidly. After about 3 to 5 years of taking aspirin, there seems to be no excess in GI bleeds. Similarly, most deaths from bleeding happen with the first month, implying underlying untreated gastric pathology, the researchers say.

GI bleeds are still the majority of the AEs caused by aspirin, but thanks to better treatments, GI bleeding and fatal bleeding have declined as much as 20% to 50% in some countries, such as Scotland, Spain, U.S., and Wales. In the risk-benefit analysis, however, the researchers say, the “undesirable effect” of prophylactic aspirin as serious as a vascular event or cancer is rare: Low-dose aspirin is associated with 1 death and 1 disabling hemorrhagic stroke per year in every 10,000 people, and that number could be lower if hypertension is treated adequately.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Source:
Elwood PC, Morgan G, Galante J, et al. PLoS One. 2016;11(11): e0166166.
doi: 10.1371/journal.pone.0166166.

Low-dose aspirin is recommended to help prevent colorectal cancer and vascular disease as well as to reduce mortality. Research suggests that low-dose aspirin also can be useful as an adjunct treatment in established cancers. The potential, however, is offset by concerns about bleeding.

Are the concerns valid? When gauging the risks vs benefits of aspirin for patients at risk for bleeding, considering not only the severity of events, but also the frequency is important, say researchers from Cardiff University, Hywel Dda University, University of Cambridge, Harvard, University of Zaragoza, University of South Wales, Swansea University, National University of Singapore, and University of Leicester.

Related: A Better Way to Predict Colorectal Cancer Relapse?

 They point out that most estimates of harm from aspirin are based on the frequency of “major” gastrointestinal (GI) bleeding together with cerebral bleeding. But they also note that although GI bleeds can be severe, they’re “acute events usually followed by recovery without sequelae.” Strokes, on the other hand, can have lasting effects in survivors; and people who survive heart attacks or cancer may require complex and lifelong interventions.

The researchers suggest weighing the risk of fatal bleeds attributable to aspirin with the severity of the disease events prevented. And the distinction between GI bleeding and fatal bleeding isn’t trivial, they contend. Studies have already shown that the risk of death from aspirin-related GI bleeds is lower than that of spontaneous GI bleeding.

To put the discussion on a more even footing, the research team looked at 11 long-term, randomized controlled trials of aspirin prophylaxis with data on fatal adverse effects (AEs). They also incorporated new data from direct e-mail contact with the authors of some of the studies.

They found that although aspirin increases the risk of GI bleeding by about 60%, low-dose aspirin is associated with a lower risk of fatality among the patients who develop GI bleeding. The researchers note that no report mentioned the use of gastric protection by proton pump inhibitor or other treatment.

Most important, the researchers say, is the finding that among all the subjects who were taking aspirin, there was no increase in death from GI bleeding compared with those randomized to take no aspirin.

Related: Colorectal Screening: Available but Underused

Also important, they add, is to bear in mind the duration of aspirin taking. Almost all studies of cancer prevention, they note, show a 3- to 5-year delay before the benefits of aspirin are clinically apparent (because the effects on cells take a while to show up, that is, as the absence of a tumor).

However, the incidence of GI bleeding attributable to aspirin seems to drop over time: Within the first month of aspirin taking, the risk increases more than 4-fold, but then declines rapidly. After about 3 to 5 years of taking aspirin, there seems to be no excess in GI bleeds. Similarly, most deaths from bleeding happen with the first month, implying underlying untreated gastric pathology, the researchers say.

GI bleeds are still the majority of the AEs caused by aspirin, but thanks to better treatments, GI bleeding and fatal bleeding have declined as much as 20% to 50% in some countries, such as Scotland, Spain, U.S., and Wales. In the risk-benefit analysis, however, the researchers say, the “undesirable effect” of prophylactic aspirin as serious as a vascular event or cancer is rare: Low-dose aspirin is associated with 1 death and 1 disabling hemorrhagic stroke per year in every 10,000 people, and that number could be lower if hypertension is treated adequately.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Source:
Elwood PC, Morgan G, Galante J, et al. PLoS One. 2016;11(11): e0166166.
doi: 10.1371/journal.pone.0166166.

Federal Practitioner recently sat down with VA Deputy Under Secretary for Health for Policy and Services Jennifer Lee, MD, at the recent Launch Pad: Pathways to Cancer Innovation summit, November 29, 2016. In the interview, Dr. Lee discussed access to clinical trials for veterans, research, and the importance of partnering with other agencies, industry, and nonprofits to further veteran cancer care.

In the year since taking over for Madhulika Agarwal, MD, MPH, in the position, Dr. Lee has provided guidance to the Under Secretary for Health on matters related to health care policy, strategic objectives, and policy requirements for legislatively mandated health care delivery programs. She also directs research and other health policy and services programs within the VHA.

Federal Practitioner recently sat down with VA Deputy Under Secretary for Health for Policy and Services Jennifer Lee, MD, at the recent Launch Pad: Pathways to Cancer Innovation summit, November 29, 2016. In the interview, Dr. Lee discussed access to clinical trials for veterans, research, and the importance of partnering with other agencies, industry, and nonprofits to further veteran cancer care.

In the year since taking over for Madhulika Agarwal, MD, MPH, in the position, Dr. Lee has provided guidance to the Under Secretary for Health on matters related to health care policy, strategic objectives, and policy requirements for legislatively mandated health care delivery programs. She also directs research and other health policy and services programs within the VHA.

Federal Practitioner recently sat down with VA Deputy Under Secretary for Health for Policy and Services Jennifer Lee, MD, at the recent Launch Pad: Pathways to Cancer Innovation summit, November 29, 2016. In the interview, Dr. Lee discussed access to clinical trials for veterans, research, and the importance of partnering with other agencies, industry, and nonprofits to further veteran cancer care.

In the year since taking over for Madhulika Agarwal, MD, MPH, in the position, Dr. Lee has provided guidance to the Under Secretary for Health on matters related to health care policy, strategic objectives, and policy requirements for legislatively mandated health care delivery programs. She also directs research and other health policy and services programs within the VHA.

 

 

HSCT preparation

Photo by Chad McNeeley

 

SAN DIEGO—Researchers believe they have identified patients with chronic myeloid leukemia (CML) who are likely to derive long-term benefit from allogeneic hematopoietic stem cell transplant (allo-HSCT).

The researchers found that CML patients have a low risk of long-term morbidity if they undergo HSCT before the age of 45, are conditioned with busulfan and cyclophosphamide (Bu/Cy), and receive a graft from a matched, related donor (MRD).

Jessica Wu, of the University of Alabama at Birmingham, presented these findings at the 2016 ASH Annual Meeting (abstract 823*).

Wu noted that allogeneic HSCT is potentially curative for CML, but this method of treatment has been on the decline since the introduction of tyrosine kinase inhibitors (TKIs). And today, few CML patients undergo allo-HSCT.

She said that although TKIs can induce remission in CML patients, the drugs also fail to eradicate leukemia, can produce side effects that impact patients’ quality of life, and come with a significant financial burden (estimated at $92,000 to $138,000 per patient per year).

With this in mind, Wu and her colleagues set out to determine if certain CML patients might benefit from allo-HSCT long-term. The team also wanted to quantify overall and cause-specific late mortality after allo-HSCT and the long-term burden of severe/life-threatening chronic health conditions after allo-HSCT.

Patient population

The researchers studied 637 CML patients treated with allo-HSCT between 1981 and 2010 at City of Hope in Duarte, California, or the University of Minnesota in Minneapolis/Saint Paul. The patients had to have survived at least 2 years post-transplant.

About 60% of patients were male, and 67% were non-Hispanic white. Their median age at HSCT was 36.4 years, and 65% received an MRD graft. Nineteen percent of patients were transplanted in 1980-1989, 52% were transplanted in 1990-1999, and 29% were transplanted in 2000-2010.

Fifty-eight percent of patients received Cy/total body irradiation (TBI), 18% received Bu/Cy, and 3% received reduced-intensity conditioning (RIC).

Sixty-one percent of patients had chronic graft-vs-host disease (cGVHD), and 32% had high-risk disease at the time of HSCT.

Survival

The patients were followed for a median of 16.7 years. Thirty percent (n=192) died after surviving at least 2 years post-HSCT.

The median time to death was 8.3 years (range, 2-29.5), and the median age at death was 49.2 (range, 7.8-69.8). At 20 years from HSCT, the overall survival was 68.6%.

HSCT recipients had a 4.4-fold increased risk of death compared with the age-, sex-, and race-matched general population.

“Non-relapse mortality was the major contributor to late mortality, with infection, second malignancies, and cGVHD being the most common causes of death,” Wu said.

Non-relapse mortality was 20%, and relapse-related mortality was 4%. Eight percent of patients died of infection, 6.3% died of cGVHD, and 3.7% died of second malignancies.

Health outcomes

Patients who were still alive at the time of the study were asked to complete the BMTSS-2 health questionnaire, which was used to examine the risk of grade 3/4 chronic health conditions.


A total of 288 patients completed the questionnaire, as did a sibling comparison group of 404 individuals.

Among the patients, the median age at allo-HSCT was 37.5 (range, 3.6-71.4), and the median duration of follow-up was 13.9 years (range, 2-34.6).

Sixty-two percent of patients received an MRD graft, and 38% had a matched, unrelated donor. Eighty-three percent of patients had TBI-based conditioning, 16% received Bu/Cy, and 2.7% received RIC.

The prevalence of grade 3/4 chronic health conditions was significantly higher among patients than among siblings—38% and 24%, respectively (P<0.0001).

The odds ratio (OR)—adjusted for age, sex, race, and socioeconomic status—was 2.7 (P<0.0001).

The cumulative incidence of any grade 3/4 condition at 20 years after HSCT was 47.2% among patients. Common conditions were diabetes (14.9%), second malignancies (12.6%), and coronary artery disease (10%).

The researchers found the risk of grade 3/4 morbidity was significantly higher for the following patient groups:

• Those age 45 and older (hazard ratio [HR]=3.3, P<0.0001)
• Patients with a matched, unrelated donor (HR=3.0, P<0.0001)
• Those who received peripheral blood or cord blood grafts as opposed to bone marrow (HR=2.7, P=0.006).

(This analysis was adjusted for race/ethnicity, sex, education, household income, insurance, cGVHD, and conditioning regimen).

Lower risk

To identify subpopulations with a reduced risk of long-term morbidity, the researchers calculated the risk in various CML patient groups compared to siblings.

The overall OR for CML patients compared with siblings was 2.7 (P<0.0001).

The OR for patients in first chronic phase who underwent HSCT before the age of 45 and had an MRD was 1.5 (P=0.1).

The OR for CML patients in first chronic phase who underwent HSCT before the age of 45, had an MRD, and received Bu/Cy conditioning was 0.8 (P=0.7).

“[W]e found that patients who received a matched, related donor transplant under the age of 45, with busulfan/cyclophosphamide, carried the same burden of morbidity as the sibling cohort,” Wu said. “These findings could help inform decisions regarding therapeutic options for the management of CML.”

Wu noted that the limited sample size in this study prevented the researchers from examining outcomes with RIC. And a lack of data at analysis prevented them from examining pre-HSCT and post-HSCT management of CML, the interval between diagnosis and HSCT, and the life-long economic burden of allo-HSCT.

However, she said data collection is ongoing, and the researchers hope to address some of these limitations.

*Information presented at the meeting differs from the abstract.

 

 

HSCT preparation

Photo by Chad McNeeley

 

SAN DIEGO—Researchers believe they have identified patients with chronic myeloid leukemia (CML) who are likely to derive long-term benefit from allogeneic hematopoietic stem cell transplant (allo-HSCT).

The researchers found that CML patients have a low risk of long-term morbidity if they undergo HSCT before the age of 45, are conditioned with busulfan and cyclophosphamide (Bu/Cy), and receive a graft from a matched, related donor (MRD).

Jessica Wu, of the University of Alabama at Birmingham, presented these findings at the 2016 ASH Annual Meeting (abstract 823*).

Wu noted that allogeneic HSCT is potentially curative for CML, but this method of treatment has been on the decline since the introduction of tyrosine kinase inhibitors (TKIs). And today, few CML patients undergo allo-HSCT.

She said that although TKIs can induce remission in CML patients, the drugs also fail to eradicate leukemia, can produce side effects that impact patients’ quality of life, and come with a significant financial burden (estimated at $92,000 to $138,000 per patient per year).

With this in mind, Wu and her colleagues set out to determine if certain CML patients might benefit from allo-HSCT long-term. The team also wanted to quantify overall and cause-specific late mortality after allo-HSCT and the long-term burden of severe/life-threatening chronic health conditions after allo-HSCT.

Patient population

The researchers studied 637 CML patients treated with allo-HSCT between 1981 and 2010 at City of Hope in Duarte, California, or the University of Minnesota in Minneapolis/Saint Paul. The patients had to have survived at least 2 years post-transplant.

About 60% of patients were male, and 67% were non-Hispanic white. Their median age at HSCT was 36.4 years, and 65% received an MRD graft. Nineteen percent of patients were transplanted in 1980-1989, 52% were transplanted in 1990-1999, and 29% were transplanted in 2000-2010.

Fifty-eight percent of patients received Cy/total body irradiation (TBI), 18% received Bu/Cy, and 3% received reduced-intensity conditioning (RIC).

Sixty-one percent of patients had chronic graft-vs-host disease (cGVHD), and 32% had high-risk disease at the time of HSCT.

Survival

The patients were followed for a median of 16.7 years. Thirty percent (n=192) died after surviving at least 2 years post-HSCT.

The median time to death was 8.3 years (range, 2-29.5), and the median age at death was 49.2 (range, 7.8-69.8). At 20 years from HSCT, the overall survival was 68.6%.

HSCT recipients had a 4.4-fold increased risk of death compared with the age-, sex-, and race-matched general population.

“Non-relapse mortality was the major contributor to late mortality, with infection, second malignancies, and cGVHD being the most common causes of death,” Wu said.

Non-relapse mortality was 20%, and relapse-related mortality was 4%. Eight percent of patients died of infection, 6.3% died of cGVHD, and 3.7% died of second malignancies.

Health outcomes

Patients who were still alive at the time of the study were asked to complete the BMTSS-2 health questionnaire, which was used to examine the risk of grade 3/4 chronic health conditions.


A total of 288 patients completed the questionnaire, as did a sibling comparison group of 404 individuals.

Among the patients, the median age at allo-HSCT was 37.5 (range, 3.6-71.4), and the median duration of follow-up was 13.9 years (range, 2-34.6).

Sixty-two percent of patients received an MRD graft, and 38% had a matched, unrelated donor. Eighty-three percent of patients had TBI-based conditioning, 16% received Bu/Cy, and 2.7% received RIC.

The prevalence of grade 3/4 chronic health conditions was significantly higher among patients than among siblings—38% and 24%, respectively (P<0.0001).

The odds ratio (OR)—adjusted for age, sex, race, and socioeconomic status—was 2.7 (P<0.0001).

The cumulative incidence of any grade 3/4 condition at 20 years after HSCT was 47.2% among patients. Common conditions were diabetes (14.9%), second malignancies (12.6%), and coronary artery disease (10%).

The researchers found the risk of grade 3/4 morbidity was significantly higher for the following patient groups:

• Those age 45 and older (hazard ratio [HR]=3.3, P<0.0001)
• Patients with a matched, unrelated donor (HR=3.0, P<0.0001)
• Those who received peripheral blood or cord blood grafts as opposed to bone marrow (HR=2.7, P=0.006).

(This analysis was adjusted for race/ethnicity, sex, education, household income, insurance, cGVHD, and conditioning regimen).

Lower risk

To identify subpopulations with a reduced risk of long-term morbidity, the researchers calculated the risk in various CML patient groups compared to siblings.

The overall OR for CML patients compared with siblings was 2.7 (P<0.0001).

The OR for patients in first chronic phase who underwent HSCT before the age of 45 and had an MRD was 1.5 (P=0.1).

The OR for CML patients in first chronic phase who underwent HSCT before the age of 45, had an MRD, and received Bu/Cy conditioning was 0.8 (P=0.7).

“[W]e found that patients who received a matched, related donor transplant under the age of 45, with busulfan/cyclophosphamide, carried the same burden of morbidity as the sibling cohort,” Wu said. “These findings could help inform decisions regarding therapeutic options for the management of CML.”

Wu noted that the limited sample size in this study prevented the researchers from examining outcomes with RIC. And a lack of data at analysis prevented them from examining pre-HSCT and post-HSCT management of CML, the interval between diagnosis and HSCT, and the life-long economic burden of allo-HSCT.

However, she said data collection is ongoing, and the researchers hope to address some of these limitations.

*Information presented at the meeting differs from the abstract.

 

 

HSCT preparation

Photo by Chad McNeeley

 

SAN DIEGO—Researchers believe they have identified patients with chronic myeloid leukemia (CML) who are likely to derive long-term benefit from allogeneic hematopoietic stem cell transplant (allo-HSCT).

The researchers found that CML patients have a low risk of long-term morbidity if they undergo HSCT before the age of 45, are conditioned with busulfan and cyclophosphamide (Bu/Cy), and receive a graft from a matched, related donor (MRD).

Jessica Wu, of the University of Alabama at Birmingham, presented these findings at the 2016 ASH Annual Meeting (abstract 823*).

Wu noted that allogeneic HSCT is potentially curative for CML, but this method of treatment has been on the decline since the introduction of tyrosine kinase inhibitors (TKIs). And today, few CML patients undergo allo-HSCT.

She said that although TKIs can induce remission in CML patients, the drugs also fail to eradicate leukemia, can produce side effects that impact patients’ quality of life, and come with a significant financial burden (estimated at $92,000 to $138,000 per patient per year).

With this in mind, Wu and her colleagues set out to determine if certain CML patients might benefit from allo-HSCT long-term. The team also wanted to quantify overall and cause-specific late mortality after allo-HSCT and the long-term burden of severe/life-threatening chronic health conditions after allo-HSCT.

Patient population

The researchers studied 637 CML patients treated with allo-HSCT between 1981 and 2010 at City of Hope in Duarte, California, or the University of Minnesota in Minneapolis/Saint Paul. The patients had to have survived at least 2 years post-transplant.

About 60% of patients were male, and 67% were non-Hispanic white. Their median age at HSCT was 36.4 years, and 65% received an MRD graft. Nineteen percent of patients were transplanted in 1980-1989, 52% were transplanted in 1990-1999, and 29% were transplanted in 2000-2010.

Fifty-eight percent of patients received Cy/total body irradiation (TBI), 18% received Bu/Cy, and 3% received reduced-intensity conditioning (RIC).

Sixty-one percent of patients had chronic graft-vs-host disease (cGVHD), and 32% had high-risk disease at the time of HSCT.

Survival

The patients were followed for a median of 16.7 years. Thirty percent (n=192) died after surviving at least 2 years post-HSCT.

The median time to death was 8.3 years (range, 2-29.5), and the median age at death was 49.2 (range, 7.8-69.8). At 20 years from HSCT, the overall survival was 68.6%.

HSCT recipients had a 4.4-fold increased risk of death compared with the age-, sex-, and race-matched general population.

“Non-relapse mortality was the major contributor to late mortality, with infection, second malignancies, and cGVHD being the most common causes of death,” Wu said.

Non-relapse mortality was 20%, and relapse-related mortality was 4%. Eight percent of patients died of infection, 6.3% died of cGVHD, and 3.7% died of second malignancies.

Health outcomes

Patients who were still alive at the time of the study were asked to complete the BMTSS-2 health questionnaire, which was used to examine the risk of grade 3/4 chronic health conditions.


A total of 288 patients completed the questionnaire, as did a sibling comparison group of 404 individuals.

Among the patients, the median age at allo-HSCT was 37.5 (range, 3.6-71.4), and the median duration of follow-up was 13.9 years (range, 2-34.6).

Sixty-two percent of patients received an MRD graft, and 38% had a matched, unrelated donor. Eighty-three percent of patients had TBI-based conditioning, 16% received Bu/Cy, and 2.7% received RIC.

The prevalence of grade 3/4 chronic health conditions was significantly higher among patients than among siblings—38% and 24%, respectively (P<0.0001).

The odds ratio (OR)—adjusted for age, sex, race, and socioeconomic status—was 2.7 (P<0.0001).

The cumulative incidence of any grade 3/4 condition at 20 years after HSCT was 47.2% among patients. Common conditions were diabetes (14.9%), second malignancies (12.6%), and coronary artery disease (10%).

The researchers found the risk of grade 3/4 morbidity was significantly higher for the following patient groups:

• Those age 45 and older (hazard ratio [HR]=3.3, P<0.0001)
• Patients with a matched, unrelated donor (HR=3.0, P<0.0001)
• Those who received peripheral blood or cord blood grafts as opposed to bone marrow (HR=2.7, P=0.006).

(This analysis was adjusted for race/ethnicity, sex, education, household income, insurance, cGVHD, and conditioning regimen).

Lower risk

To identify subpopulations with a reduced risk of long-term morbidity, the researchers calculated the risk in various CML patient groups compared to siblings.

The overall OR for CML patients compared with siblings was 2.7 (P<0.0001).

The OR for patients in first chronic phase who underwent HSCT before the age of 45 and had an MRD was 1.5 (P=0.1).

The OR for CML patients in first chronic phase who underwent HSCT before the age of 45, had an MRD, and received Bu/Cy conditioning was 0.8 (P=0.7).

“[W]e found that patients who received a matched, related donor transplant under the age of 45, with busulfan/cyclophosphamide, carried the same burden of morbidity as the sibling cohort,” Wu said. “These findings could help inform decisions regarding therapeutic options for the management of CML.”

Wu noted that the limited sample size in this study prevented the researchers from examining outcomes with RIC. And a lack of data at analysis prevented them from examining pre-HSCT and post-HSCT management of CML, the interval between diagnosis and HSCT, and the life-long economic burden of allo-HSCT.

However, she said data collection is ongoing, and the researchers hope to address some of these limitations.

*Information presented at the meeting differs from the abstract.

Antihemophilic factor

Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.

Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*

*Stasyshyn O et al; rVIII-SingleChain, results of the pivotal efficacy data from a phase III PK, efficacy and safety clinical study in children less than 12 years of age with severe hemophilia A; WFH 2016 World Congress, July 2016.

Antihemophilic factor

Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.

Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*

*Stasyshyn O et al; rVIII-SingleChain, results of the pivotal efficacy data from a phase III PK, efficacy and safety clinical study in children less than 12 years of age with severe hemophilia A; WFH 2016 World Congress, July 2016.

Antihemophilic factor

Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.

Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*

*Stasyshyn O et al; rVIII-SingleChain, results of the pivotal efficacy data from a phase III PK, efficacy and safety clinical study in children less than 12 years of age with severe hemophilia A; WFH 2016 World Congress, July 2016.

 

 

Micrograph showing FL

 

Patients with transformed follicular lymphoma (FL) and FL patients with early progression have “widely divergent patterns of clonal

dynamics,” according to researchers.

The team investigated the molecular events underlying transformation and early progression in FL and found that disparate evolutionary trajectories and mutational profiles drive these 2 distinct clinical endpoints.

Sohrab Shah, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues reported these findings in PLOS Medicine.

The researchers used whole-genome sequencing to analyze tumor specimens and matched normal specimens from 41 FL patients.

The team then classified the patients according to the following clinical endpoints:

• Patients who presented with transformation (n=15)
• Patients who experienced tumor progression within 2.5 years of starting treatment, without evidence of transformation (n=6)
• Patients who had neither transformation nor progression up to 5 years post-diagnosis (n=20).

The researchers also used targeted capture sequencing of known FL-associated genes in a larger cohort of 277 FL patients (395 samples) to investigate discrete genetic events that drive transformation and early progression.

Results showed that tumors that progress early evolve in different ways from those that transform.

The team found that, for tumors that transform, the cells or clones that constitute the majority of the aggressive tumor were extremely rare at diagnosis, if they were present at all.

In contrast, for early progressive FL, the clonal architecture remained similar from the time of diagnosis to relapse, indicating that the diagnostic tumor may already contain the properties that confer resistance to treatment.

Analysis of the larger cohort revealed genes and biological processes that were associated with transformation and progression.

The researchers identified 12 genes that were more commonly mutated at the time of transformation than the time of diagnosis—TP53, B2M, EZH2, MYC, CCND3, EBF1, PIM1, GNA13, ITPKB, CHD8, S1PR2, and P2RY8.

The team said their findings suggest that defective DNA damage response, increased proliferation, escape from immune surveillance, and loss of confinement within the germinal center are key features that drive histological transformation from indolent to aggressive lymphoma.

The researchers also identified 10 genes that were more commonly mutated in patients with early progression than in patients with late/no progression—B2M, BTG1, FAS, IKZF3, KMT2C, MKI67, MYD88, SOCS1, TP53, and XBP1.

The team noted that most patients with early progression (80%) had mutations in at least 1 of these 10 genes, but none of the genes were mutated at a frequency greater than 27%. This suggests that early progression is related to relatively infrequent genetic alterations.

The researchers said these findings provide a basis for future research on prognostic assay development and potential strategies for monitoring and treatment of patients with FL.

 

 

Micrograph showing FL

 

Patients with transformed follicular lymphoma (FL) and FL patients with early progression have “widely divergent patterns of clonal

dynamics,” according to researchers.

The team investigated the molecular events underlying transformation and early progression in FL and found that disparate evolutionary trajectories and mutational profiles drive these 2 distinct clinical endpoints.

Sohrab Shah, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues reported these findings in PLOS Medicine.

The researchers used whole-genome sequencing to analyze tumor specimens and matched normal specimens from 41 FL patients.

The team then classified the patients according to the following clinical endpoints:

• Patients who presented with transformation (n=15)
• Patients who experienced tumor progression within 2.5 years of starting treatment, without evidence of transformation (n=6)
• Patients who had neither transformation nor progression up to 5 years post-diagnosis (n=20).

The researchers also used targeted capture sequencing of known FL-associated genes in a larger cohort of 277 FL patients (395 samples) to investigate discrete genetic events that drive transformation and early progression.

Results showed that tumors that progress early evolve in different ways from those that transform.

The team found that, for tumors that transform, the cells or clones that constitute the majority of the aggressive tumor were extremely rare at diagnosis, if they were present at all.

In contrast, for early progressive FL, the clonal architecture remained similar from the time of diagnosis to relapse, indicating that the diagnostic tumor may already contain the properties that confer resistance to treatment.

Analysis of the larger cohort revealed genes and biological processes that were associated with transformation and progression.

The researchers identified 12 genes that were more commonly mutated at the time of transformation than the time of diagnosis—TP53, B2M, EZH2, MYC, CCND3, EBF1, PIM1, GNA13, ITPKB, CHD8, S1PR2, and P2RY8.

The team said their findings suggest that defective DNA damage response, increased proliferation, escape from immune surveillance, and loss of confinement within the germinal center are key features that drive histological transformation from indolent to aggressive lymphoma.

The researchers also identified 10 genes that were more commonly mutated in patients with early progression than in patients with late/no progression—B2M, BTG1, FAS, IKZF3, KMT2C, MKI67, MYD88, SOCS1, TP53, and XBP1.

The team noted that most patients with early progression (80%) had mutations in at least 1 of these 10 genes, but none of the genes were mutated at a frequency greater than 27%. This suggests that early progression is related to relatively infrequent genetic alterations.

The researchers said these findings provide a basis for future research on prognostic assay development and potential strategies for monitoring and treatment of patients with FL.

 

 

Micrograph showing FL

 

Patients with transformed follicular lymphoma (FL) and FL patients with early progression have “widely divergent patterns of clonal

dynamics,” according to researchers.

The team investigated the molecular events underlying transformation and early progression in FL and found that disparate evolutionary trajectories and mutational profiles drive these 2 distinct clinical endpoints.

Sohrab Shah, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues reported these findings in PLOS Medicine.

The researchers used whole-genome sequencing to analyze tumor specimens and matched normal specimens from 41 FL patients.

The team then classified the patients according to the following clinical endpoints:

• Patients who presented with transformation (n=15)
• Patients who experienced tumor progression within 2.5 years of starting treatment, without evidence of transformation (n=6)
• Patients who had neither transformation nor progression up to 5 years post-diagnosis (n=20).

The researchers also used targeted capture sequencing of known FL-associated genes in a larger cohort of 277 FL patients (395 samples) to investigate discrete genetic events that drive transformation and early progression.

Results showed that tumors that progress early evolve in different ways from those that transform.

The team found that, for tumors that transform, the cells or clones that constitute the majority of the aggressive tumor were extremely rare at diagnosis, if they were present at all.

In contrast, for early progressive FL, the clonal architecture remained similar from the time of diagnosis to relapse, indicating that the diagnostic tumor may already contain the properties that confer resistance to treatment.

Analysis of the larger cohort revealed genes and biological processes that were associated with transformation and progression.

The researchers identified 12 genes that were more commonly mutated at the time of transformation than the time of diagnosis—TP53, B2M, EZH2, MYC, CCND3, EBF1, PIM1, GNA13, ITPKB, CHD8, S1PR2, and P2RY8.

The team said their findings suggest that defective DNA damage response, increased proliferation, escape from immune surveillance, and loss of confinement within the germinal center are key features that drive histological transformation from indolent to aggressive lymphoma.

The researchers also identified 10 genes that were more commonly mutated in patients with early progression than in patients with late/no progression—B2M, BTG1, FAS, IKZF3, KMT2C, MKI67, MYD88, SOCS1, TP53, and XBP1.

The team noted that most patients with early progression (80%) had mutations in at least 1 of these 10 genes, but none of the genes were mutated at a frequency greater than 27%. This suggests that early progression is related to relatively infrequent genetic alterations.

The researchers said these findings provide a basis for future research on prognostic assay development and potential strategies for monitoring and treatment of patients with FL.

Chemotherapy drugs

A digital health technology platform may prove useful for optimizing treatment of acute lymphoblastic leukemia (ALL), according to research published in SLAS Technology.

The platform is based on phenotypic personalized medicine (PPM), in which a patient’s response to treatment can be visually represented in the shape of a parabola.

The graph plots the drug dose along the horizontal axis and the patient’s response on the vertical axis.

Researchers said PPM has the ability to accurately identify a person’s optimal drug and dose combinations throughout an entire course of treatment.

“Phenotypic personalized medicine is like turbocharged artificial intelligence,” said study author Dean Ho, PhD, of the University of California, Los Angeles.

“It personalizes combination therapy to optimize efficacy and safety. The ability for our technology to continuously pinpoint the proper dosages of multiple drugs from such a large pool of possible combinations overcomes a challenge that is substantially more difficult than finding a needle in a haystack.”

In this study, Dr Ho and his colleagues used PPM to (retrospectively) individualize drug ratios/dosages in 2 pediatric patients with standard-risk ALL.

The researchers looked at the patients’ records to examine the administration of 4-drug maintenance regimens (dexamethasone, vincristine, mercaptopurine, and methotrexate).

The team said the drug doses served as the inputs, and maintaining absolute neutrophil counts and platelet counts within target ranges served as the outputs for optimization.

Using PPM, the researchers generated individualized 3-dimensional maps to determine the optimal drug ratios.

The team found their technology-suggested drug dosages were as much as 40% lower than clinical chemotherapy dosages, but they still maintained target neutrophil/platelet levels.

The parabolas showed that markedly different dosages of each drug were required to maintain normal cell counts for each patient.

The researchers said their results demonstrate a clear need to personalize ALL treatment and will serve as a foundation for a pending clinical trial to optimize multidrug chemotherapy.

“PPM has the ability to personalize combination therapy for a wide spectrum of diseases, making it a broadly applicable technology,” said study author Chih-Ming Ho, PhD, of the University of California, Los Angeles.

“The fact that we don’t need any information pertaining to a disease’s biological process in order to optimize and personalize treatment is a revolutionary advance. We’re at the interface of digital health and cancer treatment.”

The research team is planning to recruit patients for a prospective trial within the next year. The technology is approved for additional infectious disease and oncology studies.

Chemotherapy drugs

A digital health technology platform may prove useful for optimizing treatment of acute lymphoblastic leukemia (ALL), according to research published in SLAS Technology.

The platform is based on phenotypic personalized medicine (PPM), in which a patient’s response to treatment can be visually represented in the shape of a parabola.

The graph plots the drug dose along the horizontal axis and the patient’s response on the vertical axis.

Researchers said PPM has the ability to accurately identify a person’s optimal drug and dose combinations throughout an entire course of treatment.

“Phenotypic personalized medicine is like turbocharged artificial intelligence,” said study author Dean Ho, PhD, of the University of California, Los Angeles.

“It personalizes combination therapy to optimize efficacy and safety. The ability for our technology to continuously pinpoint the proper dosages of multiple drugs from such a large pool of possible combinations overcomes a challenge that is substantially more difficult than finding a needle in a haystack.”

In this study, Dr Ho and his colleagues used PPM to (retrospectively) individualize drug ratios/dosages in 2 pediatric patients with standard-risk ALL.

The researchers looked at the patients’ records to examine the administration of 4-drug maintenance regimens (dexamethasone, vincristine, mercaptopurine, and methotrexate).

The team said the drug doses served as the inputs, and maintaining absolute neutrophil counts and platelet counts within target ranges served as the outputs for optimization.

Using PPM, the researchers generated individualized 3-dimensional maps to determine the optimal drug ratios.

The team found their technology-suggested drug dosages were as much as 40% lower than clinical chemotherapy dosages, but they still maintained target neutrophil/platelet levels.

The parabolas showed that markedly different dosages of each drug were required to maintain normal cell counts for each patient.

The researchers said their results demonstrate a clear need to personalize ALL treatment and will serve as a foundation for a pending clinical trial to optimize multidrug chemotherapy.

“PPM has the ability to personalize combination therapy for a wide spectrum of diseases, making it a broadly applicable technology,” said study author Chih-Ming Ho, PhD, of the University of California, Los Angeles.

“The fact that we don’t need any information pertaining to a disease’s biological process in order to optimize and personalize treatment is a revolutionary advance. We’re at the interface of digital health and cancer treatment.”

The research team is planning to recruit patients for a prospective trial within the next year. The technology is approved for additional infectious disease and oncology studies.

Chemotherapy drugs

A digital health technology platform may prove useful for optimizing treatment of acute lymphoblastic leukemia (ALL), according to research published in SLAS Technology.

The platform is based on phenotypic personalized medicine (PPM), in which a patient’s response to treatment can be visually represented in the shape of a parabola.

The graph plots the drug dose along the horizontal axis and the patient’s response on the vertical axis.

Researchers said PPM has the ability to accurately identify a person’s optimal drug and dose combinations throughout an entire course of treatment.

“Phenotypic personalized medicine is like turbocharged artificial intelligence,” said study author Dean Ho, PhD, of the University of California, Los Angeles.

“It personalizes combination therapy to optimize efficacy and safety. The ability for our technology to continuously pinpoint the proper dosages of multiple drugs from such a large pool of possible combinations overcomes a challenge that is substantially more difficult than finding a needle in a haystack.”

In this study, Dr Ho and his colleagues used PPM to (retrospectively) individualize drug ratios/dosages in 2 pediatric patients with standard-risk ALL.

The researchers looked at the patients’ records to examine the administration of 4-drug maintenance regimens (dexamethasone, vincristine, mercaptopurine, and methotrexate).

The team said the drug doses served as the inputs, and maintaining absolute neutrophil counts and platelet counts within target ranges served as the outputs for optimization.

Using PPM, the researchers generated individualized 3-dimensional maps to determine the optimal drug ratios.

The team found their technology-suggested drug dosages were as much as 40% lower than clinical chemotherapy dosages, but they still maintained target neutrophil/platelet levels.

The parabolas showed that markedly different dosages of each drug were required to maintain normal cell counts for each patient.

The researchers said their results demonstrate a clear need to personalize ALL treatment and will serve as a foundation for a pending clinical trial to optimize multidrug chemotherapy.

“PPM has the ability to personalize combination therapy for a wide spectrum of diseases, making it a broadly applicable technology,” said study author Chih-Ming Ho, PhD, of the University of California, Los Angeles.

“The fact that we don’t need any information pertaining to a disease’s biological process in order to optimize and personalize treatment is a revolutionary advance. We’re at the interface of digital health and cancer treatment.”

The research team is planning to recruit patients for a prospective trial within the next year. The technology is approved for additional infectious disease and oncology studies.

Accompanied by family, a 68-year-old man presents for evaluation of changes on the left side of his face. His relatives, who have not seen him in years, find the changes quite alarming; the patient, however, is quite sure he has “looked this way for a while.” In any case, he has no associated symptoms.

He does have numerous other health problems, including hypertension, heart disease, and a 50–pack-year history of smoking. He has spent a great deal of time in the sun over the years, particularly when he drove a dump truck for work.

EXAMINATION
The left side of the patient’s face is covered with open and closed comedones superimposed on thickened, yellowed skin. Poikilodermatous changes and multiple telangiectasias can also be seen. The right side of his face demonstrates minor skin changes relative to the left.

What is the diagnosis?

Studies in the US show that FRS affects nearly 6% of white adults (usually men) older than 60. Radiation therapy (eg, for squamous cell carcinoma) can produce similar effects.

Needless to say, smoking cessation is advisable. Beyond that, treatment involves preventing further sun damage and applying retinoid preparations, such as tretinoin or adapalene. Depending on the desired level of improvement, comedones may need to be surgically ablated.

TAKE-HOME LEARNING POINTS
• Favre-Racouchot syndrome (FRS) manifests with collections of open and closed comedones on sun-damaged facial skin.
• Most FRS patients are white male smokers older than 60.
• FRS is usually unilateral, resulting from overexposure to sunlight through a vehicle’s driver-side window; however, people working outdoors (eg, fishermen) can develop it over the whole face.

Accompanied by family, a 68-year-old man presents for evaluation of changes on the left side of his face. His relatives, who have not seen him in years, find the changes quite alarming; the patient, however, is quite sure he has “looked this way for a while.” In any case, he has no associated symptoms.

He does have numerous other health problems, including hypertension, heart disease, and a 50–pack-year history of smoking. He has spent a great deal of time in the sun over the years, particularly when he drove a dump truck for work.

EXAMINATION
The left side of the patient’s face is covered with open and closed comedones superimposed on thickened, yellowed skin. Poikilodermatous changes and multiple telangiectasias can also be seen. The right side of his face demonstrates minor skin changes relative to the left.

What is the diagnosis?

Studies in the US show that FRS affects nearly 6% of white adults (usually men) older than 60. Radiation therapy (eg, for squamous cell carcinoma) can produce similar effects.

Needless to say, smoking cessation is advisable. Beyond that, treatment involves preventing further sun damage and applying retinoid preparations, such as tretinoin or adapalene. Depending on the desired level of improvement, comedones may need to be surgically ablated.

TAKE-HOME LEARNING POINTS
• Favre-Racouchot syndrome (FRS) manifests with collections of open and closed comedones on sun-damaged facial skin.
• Most FRS patients are white male smokers older than 60.
• FRS is usually unilateral, resulting from overexposure to sunlight through a vehicle’s driver-side window; however, people working outdoors (eg, fishermen) can develop it over the whole face.

Accompanied by family, a 68-year-old man presents for evaluation of changes on the left side of his face. His relatives, who have not seen him in years, find the changes quite alarming; the patient, however, is quite sure he has “looked this way for a while.” In any case, he has no associated symptoms.

He does have numerous other health problems, including hypertension, heart disease, and a 50–pack-year history of smoking. He has spent a great deal of time in the sun over the years, particularly when he drove a dump truck for work.

EXAMINATION
The left side of the patient’s face is covered with open and closed comedones superimposed on thickened, yellowed skin. Poikilodermatous changes and multiple telangiectasias can also be seen. The right side of his face demonstrates minor skin changes relative to the left.

What is the diagnosis?

Studies in the US show that FRS affects nearly 6% of white adults (usually men) older than 60. Radiation therapy (eg, for squamous cell carcinoma) can produce similar effects.

Needless to say, smoking cessation is advisable. Beyond that, treatment involves preventing further sun damage and applying retinoid preparations, such as tretinoin or adapalene. Depending on the desired level of improvement, comedones may need to be surgically ablated.

TAKE-HOME LEARNING POINTS
• Favre-Racouchot syndrome (FRS) manifests with collections of open and closed comedones on sun-damaged facial skin.
• Most FRS patients are white male smokers older than 60.
• FRS is usually unilateral, resulting from overexposure to sunlight through a vehicle’s driver-side window; however, people working outdoors (eg, fishermen) can develop it over the whole face.