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In Bladder Cancer, New Systemic Treatments Arise
MINNEAPOLIS -- A new era of systemic treatment for bladder cancer has arrived, a US Department of Veterans Affairs (VA) hematologist/oncologist told colleagues, and more changes await on the horizon.
“After a historically long dry spell, you're seeing novel drugs and combinations under investigation,” said Elizabeth Henry, MD, of Edward Hines, Jr. VA Hospital and Loyola University Medical Center in Chicago, Illinois, in a presentation at the annual meeting of the Association of VA Hematology/Oncology. “Our treatment paradigm will almost certainly continue to change.”
There’s a major need for new approaches in bladder cancer, Dr. Henry said. While the median survival for patients with metastatic disease treated has risen, it remains low at about 15 months. And, she said, the 5-year survival rate is about 15% with modern treatments.
Platinum-based chemotherapy is still the first-line treatment, she said, and cisplatin-based combos remain the standard. However, many patients are not eligible to take cisplatin because of factors such as reduced performance status, impaired renal function, peripheral neuropathy, hearing loss and heart failure. “Many patients have renal insufficiency and are platinum ineligible from the get-go,” Dr. Henry said.
In these patients, immune checkpoint inhibitors are an option, but research suggests they may lead to poorer survival in those with PDL1-low tumors. In 2018, the US Food and Drug Administration (FDA) advised their use as first-line treatment only in PDL1-high, cisplatin-ineligible patients or those who can’t undergo chemotherapy, she said.
As second-line therapy after platinum treatment, Dr. Henry said, several drugs targeting the PD1/PDL1 pathway are now FDA-approved with response rates at 15% to 25%; only 1 (pembrolizumab) has level 1 evidence from a phase 3 randomized clinical trial.
Single-agent chemotherapy is an option for patients who have worsened or cannot undergo treatment with immune checkpoint inhibitors. However, according to Dr. Henry, response rates are low (about 10%-15%) and there's no prospective or randomized control trial data showing a survival benefit.
What now? Targeted approaches are entering the picture. For example, fibroblast growth factor receptor inhibitors, which target a pathway that often mutates in bladder cancer. One drug, erdafitinib (Balversa), received FDA approval earlier this year based on a phase 2 trial data that showed an objective response rate (ORR) of 40%. Dr. Henry cautioned that unusual adverse effects can occur, including hyperphosphatemia (a disorder that boosts phosphate levels), ocular toxicity (which can lead to retinal detachment), and toxicity of the skin and hair.
“Patients need to be closely followed if they're starting this as a targeted drug,” Dr. Henry said.
Anti-Nectin-4 antibody drug conjugate, which targets urothelial carcinomas with uniformly high expression of the Nectin-4 cell surface marker, also is showing promise. Recent research suggests a “remarkable” ORR of 42% and nearly 8 months duration of response, she said.
Adverse effects include rash, peripheral neuropathy, and hyperglycemia. “Overall, this is thought to be a relatively well-tolerated therapy,” she said.
In terms of other advances, “we are moving closer to an era of molecular subtype-specific therapeutic strategies,” Dr. Henry said, and the National Comprehensive Cancer Network recommends early molecular testing in stage IIIB/IV urothelial cancer. “It can help facilitate treatment decisions and prevent delays in later lines of therapy, although we're still limited by development of individualized biomarker assays for specific drugs.”
Moving forward, she said, “continued research is needed to learn how to incorporate predictive molecular profiles to optimize treatment selection.”
Dr. Henry reported no relevant disclosures.
MINNEAPOLIS -- A new era of systemic treatment for bladder cancer has arrived, a US Department of Veterans Affairs (VA) hematologist/oncologist told colleagues, and more changes await on the horizon.
“After a historically long dry spell, you're seeing novel drugs and combinations under investigation,” said Elizabeth Henry, MD, of Edward Hines, Jr. VA Hospital and Loyola University Medical Center in Chicago, Illinois, in a presentation at the annual meeting of the Association of VA Hematology/Oncology. “Our treatment paradigm will almost certainly continue to change.”
There’s a major need for new approaches in bladder cancer, Dr. Henry said. While the median survival for patients with metastatic disease treated has risen, it remains low at about 15 months. And, she said, the 5-year survival rate is about 15% with modern treatments.
Platinum-based chemotherapy is still the first-line treatment, she said, and cisplatin-based combos remain the standard. However, many patients are not eligible to take cisplatin because of factors such as reduced performance status, impaired renal function, peripheral neuropathy, hearing loss and heart failure. “Many patients have renal insufficiency and are platinum ineligible from the get-go,” Dr. Henry said.
In these patients, immune checkpoint inhibitors are an option, but research suggests they may lead to poorer survival in those with PDL1-low tumors. In 2018, the US Food and Drug Administration (FDA) advised their use as first-line treatment only in PDL1-high, cisplatin-ineligible patients or those who can’t undergo chemotherapy, she said.
As second-line therapy after platinum treatment, Dr. Henry said, several drugs targeting the PD1/PDL1 pathway are now FDA-approved with response rates at 15% to 25%; only 1 (pembrolizumab) has level 1 evidence from a phase 3 randomized clinical trial.
Single-agent chemotherapy is an option for patients who have worsened or cannot undergo treatment with immune checkpoint inhibitors. However, according to Dr. Henry, response rates are low (about 10%-15%) and there's no prospective or randomized control trial data showing a survival benefit.
What now? Targeted approaches are entering the picture. For example, fibroblast growth factor receptor inhibitors, which target a pathway that often mutates in bladder cancer. One drug, erdafitinib (Balversa), received FDA approval earlier this year based on a phase 2 trial data that showed an objective response rate (ORR) of 40%. Dr. Henry cautioned that unusual adverse effects can occur, including hyperphosphatemia (a disorder that boosts phosphate levels), ocular toxicity (which can lead to retinal detachment), and toxicity of the skin and hair.
“Patients need to be closely followed if they're starting this as a targeted drug,” Dr. Henry said.
Anti-Nectin-4 antibody drug conjugate, which targets urothelial carcinomas with uniformly high expression of the Nectin-4 cell surface marker, also is showing promise. Recent research suggests a “remarkable” ORR of 42% and nearly 8 months duration of response, she said.
Adverse effects include rash, peripheral neuropathy, and hyperglycemia. “Overall, this is thought to be a relatively well-tolerated therapy,” she said.
In terms of other advances, “we are moving closer to an era of molecular subtype-specific therapeutic strategies,” Dr. Henry said, and the National Comprehensive Cancer Network recommends early molecular testing in stage IIIB/IV urothelial cancer. “It can help facilitate treatment decisions and prevent delays in later lines of therapy, although we're still limited by development of individualized biomarker assays for specific drugs.”
Moving forward, she said, “continued research is needed to learn how to incorporate predictive molecular profiles to optimize treatment selection.”
Dr. Henry reported no relevant disclosures.
MINNEAPOLIS -- A new era of systemic treatment for bladder cancer has arrived, a US Department of Veterans Affairs (VA) hematologist/oncologist told colleagues, and more changes await on the horizon.
“After a historically long dry spell, you're seeing novel drugs and combinations under investigation,” said Elizabeth Henry, MD, of Edward Hines, Jr. VA Hospital and Loyola University Medical Center in Chicago, Illinois, in a presentation at the annual meeting of the Association of VA Hematology/Oncology. “Our treatment paradigm will almost certainly continue to change.”
There’s a major need for new approaches in bladder cancer, Dr. Henry said. While the median survival for patients with metastatic disease treated has risen, it remains low at about 15 months. And, she said, the 5-year survival rate is about 15% with modern treatments.
Platinum-based chemotherapy is still the first-line treatment, she said, and cisplatin-based combos remain the standard. However, many patients are not eligible to take cisplatin because of factors such as reduced performance status, impaired renal function, peripheral neuropathy, hearing loss and heart failure. “Many patients have renal insufficiency and are platinum ineligible from the get-go,” Dr. Henry said.
In these patients, immune checkpoint inhibitors are an option, but research suggests they may lead to poorer survival in those with PDL1-low tumors. In 2018, the US Food and Drug Administration (FDA) advised their use as first-line treatment only in PDL1-high, cisplatin-ineligible patients or those who can’t undergo chemotherapy, she said.
As second-line therapy after platinum treatment, Dr. Henry said, several drugs targeting the PD1/PDL1 pathway are now FDA-approved with response rates at 15% to 25%; only 1 (pembrolizumab) has level 1 evidence from a phase 3 randomized clinical trial.
Single-agent chemotherapy is an option for patients who have worsened or cannot undergo treatment with immune checkpoint inhibitors. However, according to Dr. Henry, response rates are low (about 10%-15%) and there's no prospective or randomized control trial data showing a survival benefit.
What now? Targeted approaches are entering the picture. For example, fibroblast growth factor receptor inhibitors, which target a pathway that often mutates in bladder cancer. One drug, erdafitinib (Balversa), received FDA approval earlier this year based on a phase 2 trial data that showed an objective response rate (ORR) of 40%. Dr. Henry cautioned that unusual adverse effects can occur, including hyperphosphatemia (a disorder that boosts phosphate levels), ocular toxicity (which can lead to retinal detachment), and toxicity of the skin and hair.
“Patients need to be closely followed if they're starting this as a targeted drug,” Dr. Henry said.
Anti-Nectin-4 antibody drug conjugate, which targets urothelial carcinomas with uniformly high expression of the Nectin-4 cell surface marker, also is showing promise. Recent research suggests a “remarkable” ORR of 42% and nearly 8 months duration of response, she said.
Adverse effects include rash, peripheral neuropathy, and hyperglycemia. “Overall, this is thought to be a relatively well-tolerated therapy,” she said.
In terms of other advances, “we are moving closer to an era of molecular subtype-specific therapeutic strategies,” Dr. Henry said, and the National Comprehensive Cancer Network recommends early molecular testing in stage IIIB/IV urothelial cancer. “It can help facilitate treatment decisions and prevent delays in later lines of therapy, although we're still limited by development of individualized biomarker assays for specific drugs.”
Moving forward, she said, “continued research is needed to learn how to incorporate predictive molecular profiles to optimize treatment selection.”
Dr. Henry reported no relevant disclosures.
Clinical Trials Should Be Standard of Care
MINNEAPOLIS -- Clinical trials should be considered standard of care in oncology, the president of the Association of VA Hematology/Oncology (AVAHO) declared, and he urged colleagues to bypass obstacles and embrace them in patient care.
Clinical trials help many people, not just those in the studies, as they are indicators of robust oncology programs. “There’s a significant correlation between clinical trial activity [at sites] and improvement in survival in cancer,” said oncologist Mark Klein, MD, of the Minneapolis VA Health Care System and University of Minnesota, in a presentation at the 2019 annual meeting of AVAHO.
But the numbers suggest that the VA has lagged behind on the clinical trial front, Dr. Klein said. He pointed to internal statistics from 2001 to 2003, reported in 2010, which found clinical trial participation rates among men in the VA were lower (0.37%) than those of the national rates (0.74%).
Specifically, the VA and national participation rates were 1.16% and 0.30%, respectively, for colorectal cancer, 0.67% and 0.30% for lung cancer, 0.70% and 0.47% for prostate cancer, 0.52% and 0.74% for myeloma. According to Dr. Klein, lung and prostate cancer account for about half of all cancer diagnoses in the VA.
But the participation rates were much higher among the VA hospitals that took part in clinical trials, he said, at 2% for colorectal cancer, 1.4% for lung cancer, 2.5% for prostate cancer, 18.2% for myeloma and 2.07% overall. These numbers make it clear, he said, that it’s possible to improve: “We can do better.”
Dr. Klein pointed to other numbers that suggest the VA facilities that do participate in clinical trials typically do not take part in more than 1 or 2. In 2016, he said, an analysis found that open interventional trials were in progress at 82 VA facilities. About 35 facilities had little activity with only 1 trial in progress. “It has changed since then, but not dramatically.”
Meanwhile, he said, 2016 numbers also showed that about two-thirds of open interventional trials in the VA only included a single VA site. “We weren’t playing together, having consortia and working as a team.”
There are obstacles to improvement, he said, and fixes will take time. “It probably takes 5, 10-plus years,” he said.
These barriers include:
- Lack of adequate trial offering. Changing regulations is key here;
- Strict eligibility criteria. Easing the criteria and more effective screening are helpful;
- Long distances to travel to cancer clinics. Telemedicine could make a difference on this front;
- Patient concerns about being a “guinea pig.” Patient education can help;
- Provider concerns such as worry about extra work. The VA can work to ease burdens and provide incentives for trial enrollment; and
- High costs. Study sponsors may pay for trial drugs, helping facilities to lower expenses or even reach cost neutrality.
There are more solutions to boost participation, Dr. Klein said, including education, engagement and partnerships.
On the partnership front, he highlighted NAVIGATE, an interagency consortium of the VA and the National Cancer Institute. This collaboration aims to boost enrollment of VA patients in clinical trials, he said, and there are designated NAVIGATE sites across the country from coast to coast.
A partnership between AVAHO and the National Association of Veterans’ Research and Education Foundations is also boosting clinical trials in VA oncology. Thanks to this partnership, 1 trial has completed accrual, 6 multisite trials are active, and 5 are starting up, according to Dr. Klein.
In the big picture, Dr. Klein said, it’s clear that “we’ve got a lot of barriers in the VA. Anybody who works in the VA knows that. But I’ve seen this meeting grow and grow, and I’ve seen teamwork and partnerships form.”
MINNEAPOLIS -- Clinical trials should be considered standard of care in oncology, the president of the Association of VA Hematology/Oncology (AVAHO) declared, and he urged colleagues to bypass obstacles and embrace them in patient care.
Clinical trials help many people, not just those in the studies, as they are indicators of robust oncology programs. “There’s a significant correlation between clinical trial activity [at sites] and improvement in survival in cancer,” said oncologist Mark Klein, MD, of the Minneapolis VA Health Care System and University of Minnesota, in a presentation at the 2019 annual meeting of AVAHO.
But the numbers suggest that the VA has lagged behind on the clinical trial front, Dr. Klein said. He pointed to internal statistics from 2001 to 2003, reported in 2010, which found clinical trial participation rates among men in the VA were lower (0.37%) than those of the national rates (0.74%).
Specifically, the VA and national participation rates were 1.16% and 0.30%, respectively, for colorectal cancer, 0.67% and 0.30% for lung cancer, 0.70% and 0.47% for prostate cancer, 0.52% and 0.74% for myeloma. According to Dr. Klein, lung and prostate cancer account for about half of all cancer diagnoses in the VA.
But the participation rates were much higher among the VA hospitals that took part in clinical trials, he said, at 2% for colorectal cancer, 1.4% for lung cancer, 2.5% for prostate cancer, 18.2% for myeloma and 2.07% overall. These numbers make it clear, he said, that it’s possible to improve: “We can do better.”
Dr. Klein pointed to other numbers that suggest the VA facilities that do participate in clinical trials typically do not take part in more than 1 or 2. In 2016, he said, an analysis found that open interventional trials were in progress at 82 VA facilities. About 35 facilities had little activity with only 1 trial in progress. “It has changed since then, but not dramatically.”
Meanwhile, he said, 2016 numbers also showed that about two-thirds of open interventional trials in the VA only included a single VA site. “We weren’t playing together, having consortia and working as a team.”
There are obstacles to improvement, he said, and fixes will take time. “It probably takes 5, 10-plus years,” he said.
These barriers include:
- Lack of adequate trial offering. Changing regulations is key here;
- Strict eligibility criteria. Easing the criteria and more effective screening are helpful;
- Long distances to travel to cancer clinics. Telemedicine could make a difference on this front;
- Patient concerns about being a “guinea pig.” Patient education can help;
- Provider concerns such as worry about extra work. The VA can work to ease burdens and provide incentives for trial enrollment; and
- High costs. Study sponsors may pay for trial drugs, helping facilities to lower expenses or even reach cost neutrality.
There are more solutions to boost participation, Dr. Klein said, including education, engagement and partnerships.
On the partnership front, he highlighted NAVIGATE, an interagency consortium of the VA and the National Cancer Institute. This collaboration aims to boost enrollment of VA patients in clinical trials, he said, and there are designated NAVIGATE sites across the country from coast to coast.
A partnership between AVAHO and the National Association of Veterans’ Research and Education Foundations is also boosting clinical trials in VA oncology. Thanks to this partnership, 1 trial has completed accrual, 6 multisite trials are active, and 5 are starting up, according to Dr. Klein.
In the big picture, Dr. Klein said, it’s clear that “we’ve got a lot of barriers in the VA. Anybody who works in the VA knows that. But I’ve seen this meeting grow and grow, and I’ve seen teamwork and partnerships form.”
MINNEAPOLIS -- Clinical trials should be considered standard of care in oncology, the president of the Association of VA Hematology/Oncology (AVAHO) declared, and he urged colleagues to bypass obstacles and embrace them in patient care.
Clinical trials help many people, not just those in the studies, as they are indicators of robust oncology programs. “There’s a significant correlation between clinical trial activity [at sites] and improvement in survival in cancer,” said oncologist Mark Klein, MD, of the Minneapolis VA Health Care System and University of Minnesota, in a presentation at the 2019 annual meeting of AVAHO.
But the numbers suggest that the VA has lagged behind on the clinical trial front, Dr. Klein said. He pointed to internal statistics from 2001 to 2003, reported in 2010, which found clinical trial participation rates among men in the VA were lower (0.37%) than those of the national rates (0.74%).
Specifically, the VA and national participation rates were 1.16% and 0.30%, respectively, for colorectal cancer, 0.67% and 0.30% for lung cancer, 0.70% and 0.47% for prostate cancer, 0.52% and 0.74% for myeloma. According to Dr. Klein, lung and prostate cancer account for about half of all cancer diagnoses in the VA.
But the participation rates were much higher among the VA hospitals that took part in clinical trials, he said, at 2% for colorectal cancer, 1.4% for lung cancer, 2.5% for prostate cancer, 18.2% for myeloma and 2.07% overall. These numbers make it clear, he said, that it’s possible to improve: “We can do better.”
Dr. Klein pointed to other numbers that suggest the VA facilities that do participate in clinical trials typically do not take part in more than 1 or 2. In 2016, he said, an analysis found that open interventional trials were in progress at 82 VA facilities. About 35 facilities had little activity with only 1 trial in progress. “It has changed since then, but not dramatically.”
Meanwhile, he said, 2016 numbers also showed that about two-thirds of open interventional trials in the VA only included a single VA site. “We weren’t playing together, having consortia and working as a team.”
There are obstacles to improvement, he said, and fixes will take time. “It probably takes 5, 10-plus years,” he said.
These barriers include:
- Lack of adequate trial offering. Changing regulations is key here;
- Strict eligibility criteria. Easing the criteria and more effective screening are helpful;
- Long distances to travel to cancer clinics. Telemedicine could make a difference on this front;
- Patient concerns about being a “guinea pig.” Patient education can help;
- Provider concerns such as worry about extra work. The VA can work to ease burdens and provide incentives for trial enrollment; and
- High costs. Study sponsors may pay for trial drugs, helping facilities to lower expenses or even reach cost neutrality.
There are more solutions to boost participation, Dr. Klein said, including education, engagement and partnerships.
On the partnership front, he highlighted NAVIGATE, an interagency consortium of the VA and the National Cancer Institute. This collaboration aims to boost enrollment of VA patients in clinical trials, he said, and there are designated NAVIGATE sites across the country from coast to coast.
A partnership between AVAHO and the National Association of Veterans’ Research and Education Foundations is also boosting clinical trials in VA oncology. Thanks to this partnership, 1 trial has completed accrual, 6 multisite trials are active, and 5 are starting up, according to Dr. Klein.
In the big picture, Dr. Klein said, it’s clear that “we’ve got a lot of barriers in the VA. Anybody who works in the VA knows that. But I’ve seen this meeting grow and grow, and I’ve seen teamwork and partnerships form.”
FDA issues warning for CDK 4/6 inhibitors
The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.
“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.
The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.
CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.
Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.
The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.
“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.
The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.
CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.
Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.
The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.
“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.
The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.
CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.
Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.
Stem cells gene edited to be HIV resistant treat ALL, but not HIV
Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.
The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.
Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.
Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.
“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.
As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.
Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.
They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.
The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .
However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 107 copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.
The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.
“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.
The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.
SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.
Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.
The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.
Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.
Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.
“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.
As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.
Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.
They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.
The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .
However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 107 copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.
The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.
“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.
The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.
SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.
Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.
The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.
Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.
Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.
“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.
As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.
Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.
They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.
The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .
However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 107 copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.
The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.
“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.
The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.
SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Donor cells depleted of the HIV coreceptor CCR5 effectively treated ALL, but not HIV.
Major finding: The patient had a sustained complete remission of ALL, but HIV persisted after transplantation.
Study details: Case report of a 27-year-old man with ALL and HIV.
Disclosures: The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.
Source: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.
Cancer Care Coordination Perspectives of Veteran Patients with Cancer
Background: Coordinating cancer care can prove especially challenging because of the complexity of both the disease and its treatment. Typically, the care of cancer patients involves multiple types of therapies and providers (surgery, radiation therapy, chemotherapy) and ongoing treatment of cancer and other health conditions. Cancer care coordination depends upon effective, regular communication among physicians, support staff, and the patient. The objective of this study is to explore veteran patients’ experiences of cancer care coordination in order to develop a deeper understanding of the issues veterans consider important and actionable.
Methods: Semi-structured interviews were conducted among patients diagnosed with cancer types and stages that commonly receive inter-disciplinary care (eg, colorectal [stage II and up], prostate [high risk], head and neck [all stages], and lung [all stages] cancer) were eligible to participate in the study. The constant comparison technique was used to identify emerging themes.
Results: Twenty-five veteran cancer patients participated in this study. Our analysis identified four general categories representing different parts of the trajectory of the patient cancer care experience in need of coordination. Each phase had a distinct set of needs and challenges. Diagnosis: After receiving a diagnosis of cancer, Veterans reported initial feelings of shock and fear. Pre-Treatment: This phase was characterized as busy and chaotic, consisting of many appointments in different locations, and ultimately left many veterans feeling a lack of control. Onset of Treatment: Uncertainty about what to expect when receiving advanced treatments, like radiation and chemotherapy, was often exacerbated by poor provider-provider communication issues. Ongoing Treatment: As treatment progressed, many veterans experienced a growing familiarity with their routine, and simultaneously, began to regain a sense of control. Care Team: Nurse navigators were considered vital to cancer care coordination. Veterans valued honesty and transparency from their providers which built a sense of trust.
Conclusion: Veterans expressed a need to have care coordination needs and steps more explicitly addressed early, as well as active mechanisms to meet those needs. The patient experience of coordination gradually improved over the course of the care trajectory, often facilitated by relationships fostered with members of the healthcare team.
Background: Coordinating cancer care can prove especially challenging because of the complexity of both the disease and its treatment. Typically, the care of cancer patients involves multiple types of therapies and providers (surgery, radiation therapy, chemotherapy) and ongoing treatment of cancer and other health conditions. Cancer care coordination depends upon effective, regular communication among physicians, support staff, and the patient. The objective of this study is to explore veteran patients’ experiences of cancer care coordination in order to develop a deeper understanding of the issues veterans consider important and actionable.
Methods: Semi-structured interviews were conducted among patients diagnosed with cancer types and stages that commonly receive inter-disciplinary care (eg, colorectal [stage II and up], prostate [high risk], head and neck [all stages], and lung [all stages] cancer) were eligible to participate in the study. The constant comparison technique was used to identify emerging themes.
Results: Twenty-five veteran cancer patients participated in this study. Our analysis identified four general categories representing different parts of the trajectory of the patient cancer care experience in need of coordination. Each phase had a distinct set of needs and challenges. Diagnosis: After receiving a diagnosis of cancer, Veterans reported initial feelings of shock and fear. Pre-Treatment: This phase was characterized as busy and chaotic, consisting of many appointments in different locations, and ultimately left many veterans feeling a lack of control. Onset of Treatment: Uncertainty about what to expect when receiving advanced treatments, like radiation and chemotherapy, was often exacerbated by poor provider-provider communication issues. Ongoing Treatment: As treatment progressed, many veterans experienced a growing familiarity with their routine, and simultaneously, began to regain a sense of control. Care Team: Nurse navigators were considered vital to cancer care coordination. Veterans valued honesty and transparency from their providers which built a sense of trust.
Conclusion: Veterans expressed a need to have care coordination needs and steps more explicitly addressed early, as well as active mechanisms to meet those needs. The patient experience of coordination gradually improved over the course of the care trajectory, often facilitated by relationships fostered with members of the healthcare team.
Background: Coordinating cancer care can prove especially challenging because of the complexity of both the disease and its treatment. Typically, the care of cancer patients involves multiple types of therapies and providers (surgery, radiation therapy, chemotherapy) and ongoing treatment of cancer and other health conditions. Cancer care coordination depends upon effective, regular communication among physicians, support staff, and the patient. The objective of this study is to explore veteran patients’ experiences of cancer care coordination in order to develop a deeper understanding of the issues veterans consider important and actionable.
Methods: Semi-structured interviews were conducted among patients diagnosed with cancer types and stages that commonly receive inter-disciplinary care (eg, colorectal [stage II and up], prostate [high risk], head and neck [all stages], and lung [all stages] cancer) were eligible to participate in the study. The constant comparison technique was used to identify emerging themes.
Results: Twenty-five veteran cancer patients participated in this study. Our analysis identified four general categories representing different parts of the trajectory of the patient cancer care experience in need of coordination. Each phase had a distinct set of needs and challenges. Diagnosis: After receiving a diagnosis of cancer, Veterans reported initial feelings of shock and fear. Pre-Treatment: This phase was characterized as busy and chaotic, consisting of many appointments in different locations, and ultimately left many veterans feeling a lack of control. Onset of Treatment: Uncertainty about what to expect when receiving advanced treatments, like radiation and chemotherapy, was often exacerbated by poor provider-provider communication issues. Ongoing Treatment: As treatment progressed, many veterans experienced a growing familiarity with their routine, and simultaneously, began to regain a sense of control. Care Team: Nurse navigators were considered vital to cancer care coordination. Veterans valued honesty and transparency from their providers which built a sense of trust.
Conclusion: Veterans expressed a need to have care coordination needs and steps more explicitly addressed early, as well as active mechanisms to meet those needs. The patient experience of coordination gradually improved over the course of the care trajectory, often facilitated by relationships fostered with members of the healthcare team.
Mediastinal Staging for SBRT in Early NSCLC: Should it be Stratified by Tumor Size and Location?
Background: Stereotactic body radiotherapy (SBRT) is standard treatment for inoperable early-stage nonsmall cell lung cancer (NSCLC) . American College of Chest Physicians (ACCP) favors non-invasive mediastinal staging for peripheral Stage IA tumors for surgical patients. However, mediastinal staging guidelines for SBRT are still elusive and benefit of endobronchial ultrasound guided transbronchial needle biopsy (EBUS/ TBNA) in addition to positron emission tomographycomputed tomography (PET/CT) remains undefined for small peripheral NSCLC.
Purppose: To evaluate our SBRT- EBUS program by comparing survival and patterns of failure in SBRT patients staged with PET/CT and EBUS/TBNA vs. PET/ CT only for < 4cm peripheral NSCLC.
Methods: Patients with early NSCLC treated with Cyberknife (CK) from October 2010 to December 2016 were queried. Those treated definitively for single, < 4cm peripheral tumors were included. Local, regional, distant recurrences and survival outcomes were compared between patients staged with PET/CT and EBUS/TBNA vs. PET/CT only, using competing risk analysis.
Results: One hundred and fifty nine patients were treated during the study period. Mediastinum was staged using PET/CT only till 2013. Ninety one patients (mean age 69 years [64-78 years]; 99 [99%] males) had peripheral single tumors of < 4 cm2. Seventy two were staged with EBUS/TBNA and PET/CT( group I) and 19 with PET/CT only (group II). Patient ,tumor and treatment characteristics, except race, were not different. At median follow-up of 5.39 years, group I vs. group II pattern of recurrence was ;any recurrence 36.1%vs.36.1%, P=0.95; local recurrence 13.9%vs.21.1%, P=0.48; regional recurrence 13.9% vs.21.1%, P=0.48; distant recurrence 25% vs.15.8%, P=0.55 respectively .Median OS for group I and group II was 2.95 years (2.37-3.80 years, 95%CI ) and 4 years (2.01-7.08 years 95%CI); P=0.54 respectively.
Conclusion: Survival outcomes and pattern of failure were not different based on type of mediastinal staging. EBUS/TBNA use can be safely stratified based on tumor location and size in this population. Therefore, for patients with single, < 4 cm2, peripheral NSCLC, non-invasive mediastinal staging with PET/CT may suffice for definitive SBRT. Future prospective studies are needed to validate our findings.
Background: Stereotactic body radiotherapy (SBRT) is standard treatment for inoperable early-stage nonsmall cell lung cancer (NSCLC) . American College of Chest Physicians (ACCP) favors non-invasive mediastinal staging for peripheral Stage IA tumors for surgical patients. However, mediastinal staging guidelines for SBRT are still elusive and benefit of endobronchial ultrasound guided transbronchial needle biopsy (EBUS/ TBNA) in addition to positron emission tomographycomputed tomography (PET/CT) remains undefined for small peripheral NSCLC.
Purppose: To evaluate our SBRT- EBUS program by comparing survival and patterns of failure in SBRT patients staged with PET/CT and EBUS/TBNA vs. PET/ CT only for < 4cm peripheral NSCLC.
Methods: Patients with early NSCLC treated with Cyberknife (CK) from October 2010 to December 2016 were queried. Those treated definitively for single, < 4cm peripheral tumors were included. Local, regional, distant recurrences and survival outcomes were compared between patients staged with PET/CT and EBUS/TBNA vs. PET/CT only, using competing risk analysis.
Results: One hundred and fifty nine patients were treated during the study period. Mediastinum was staged using PET/CT only till 2013. Ninety one patients (mean age 69 years [64-78 years]; 99 [99%] males) had peripheral single tumors of < 4 cm2. Seventy two were staged with EBUS/TBNA and PET/CT( group I) and 19 with PET/CT only (group II). Patient ,tumor and treatment characteristics, except race, were not different. At median follow-up of 5.39 years, group I vs. group II pattern of recurrence was ;any recurrence 36.1%vs.36.1%, P=0.95; local recurrence 13.9%vs.21.1%, P=0.48; regional recurrence 13.9% vs.21.1%, P=0.48; distant recurrence 25% vs.15.8%, P=0.55 respectively .Median OS for group I and group II was 2.95 years (2.37-3.80 years, 95%CI ) and 4 years (2.01-7.08 years 95%CI); P=0.54 respectively.
Conclusion: Survival outcomes and pattern of failure were not different based on type of mediastinal staging. EBUS/TBNA use can be safely stratified based on tumor location and size in this population. Therefore, for patients with single, < 4 cm2, peripheral NSCLC, non-invasive mediastinal staging with PET/CT may suffice for definitive SBRT. Future prospective studies are needed to validate our findings.
Background: Stereotactic body radiotherapy (SBRT) is standard treatment for inoperable early-stage nonsmall cell lung cancer (NSCLC) . American College of Chest Physicians (ACCP) favors non-invasive mediastinal staging for peripheral Stage IA tumors for surgical patients. However, mediastinal staging guidelines for SBRT are still elusive and benefit of endobronchial ultrasound guided transbronchial needle biopsy (EBUS/ TBNA) in addition to positron emission tomographycomputed tomography (PET/CT) remains undefined for small peripheral NSCLC.
Purppose: To evaluate our SBRT- EBUS program by comparing survival and patterns of failure in SBRT patients staged with PET/CT and EBUS/TBNA vs. PET/ CT only for < 4cm peripheral NSCLC.
Methods: Patients with early NSCLC treated with Cyberknife (CK) from October 2010 to December 2016 were queried. Those treated definitively for single, < 4cm peripheral tumors were included. Local, regional, distant recurrences and survival outcomes were compared between patients staged with PET/CT and EBUS/TBNA vs. PET/CT only, using competing risk analysis.
Results: One hundred and fifty nine patients were treated during the study period. Mediastinum was staged using PET/CT only till 2013. Ninety one patients (mean age 69 years [64-78 years]; 99 [99%] males) had peripheral single tumors of < 4 cm2. Seventy two were staged with EBUS/TBNA and PET/CT( group I) and 19 with PET/CT only (group II). Patient ,tumor and treatment characteristics, except race, were not different. At median follow-up of 5.39 years, group I vs. group II pattern of recurrence was ;any recurrence 36.1%vs.36.1%, P=0.95; local recurrence 13.9%vs.21.1%, P=0.48; regional recurrence 13.9% vs.21.1%, P=0.48; distant recurrence 25% vs.15.8%, P=0.55 respectively .Median OS for group I and group II was 2.95 years (2.37-3.80 years, 95%CI ) and 4 years (2.01-7.08 years 95%CI); P=0.54 respectively.
Conclusion: Survival outcomes and pattern of failure were not different based on type of mediastinal staging. EBUS/TBNA use can be safely stratified based on tumor location and size in this population. Therefore, for patients with single, < 4 cm2, peripheral NSCLC, non-invasive mediastinal staging with PET/CT may suffice for definitive SBRT. Future prospective studies are needed to validate our findings.
Prognostic significance of primary tumor location in breast cancer: An Analysis of the National Cancer Database (NCDB)
Background: The prognostic implication of tumor location in breast cancer remains unclear. Previous studies suggested that inner and lower quadrant-located tumors were associated with decreased survival.
Methods: The NCDB was quired to identify AJCC clinical stage I-III first female breast cancer patients with unilateral disease who underwent breast-conserving surgery from 2010 to 2016. Three mutually exclusive groups were created based on tumor location, which included outer (upper and lower outer quadrants), central, and inner (upper and lower inner quadrants) zones of the breast. Clinical and demographic variables were obtained. Unadjusted survival differences were examined with Kaplan- Meier method. Multivariate Cox regression model was employed to examine the association between zone group and survival.
Results: 125,800 patients were identified including 83,558 (66.4%), 6,764 (5.4%), and 35,449 (28.2%) patients within the outer, central, and inner zones. There was evidence of a difference in age and tumor size based on site (P<0.001). It was also found that there was an association between tumor zone and each of the following (P<0.05): race and ethnicity, Charlson-Deyo score, insurance, income, education, facility type, laterality, histology, utilization of chemotherapy, ER status, PR status, and HER2 status. There was no relationship between site and unadjusted survival (P=0.905). After adjusting for all else, a 5.7% decreased the risk of death was found upon the comparison of the outer vs. inner zone of the breast (95% CI: 0.4%-11.8%; P=0.037). In general, older African American Medicaid patients with increased Charlson-Deyo scores and hormone receptor-negative breast cancers from lower-income areas had decreased survival.
Conclusion: Outer zone breast cancer has a more favorable survival advantage when compared with inner zone cancers. A finding that warrants re-evaluation of the management approach to inner zone breast cancer.
Background: The prognostic implication of tumor location in breast cancer remains unclear. Previous studies suggested that inner and lower quadrant-located tumors were associated with decreased survival.
Methods: The NCDB was quired to identify AJCC clinical stage I-III first female breast cancer patients with unilateral disease who underwent breast-conserving surgery from 2010 to 2016. Three mutually exclusive groups were created based on tumor location, which included outer (upper and lower outer quadrants), central, and inner (upper and lower inner quadrants) zones of the breast. Clinical and demographic variables were obtained. Unadjusted survival differences were examined with Kaplan- Meier method. Multivariate Cox regression model was employed to examine the association between zone group and survival.
Results: 125,800 patients were identified including 83,558 (66.4%), 6,764 (5.4%), and 35,449 (28.2%) patients within the outer, central, and inner zones. There was evidence of a difference in age and tumor size based on site (P<0.001). It was also found that there was an association between tumor zone and each of the following (P<0.05): race and ethnicity, Charlson-Deyo score, insurance, income, education, facility type, laterality, histology, utilization of chemotherapy, ER status, PR status, and HER2 status. There was no relationship between site and unadjusted survival (P=0.905). After adjusting for all else, a 5.7% decreased the risk of death was found upon the comparison of the outer vs. inner zone of the breast (95% CI: 0.4%-11.8%; P=0.037). In general, older African American Medicaid patients with increased Charlson-Deyo scores and hormone receptor-negative breast cancers from lower-income areas had decreased survival.
Conclusion: Outer zone breast cancer has a more favorable survival advantage when compared with inner zone cancers. A finding that warrants re-evaluation of the management approach to inner zone breast cancer.
Background: The prognostic implication of tumor location in breast cancer remains unclear. Previous studies suggested that inner and lower quadrant-located tumors were associated with decreased survival.
Methods: The NCDB was quired to identify AJCC clinical stage I-III first female breast cancer patients with unilateral disease who underwent breast-conserving surgery from 2010 to 2016. Three mutually exclusive groups were created based on tumor location, which included outer (upper and lower outer quadrants), central, and inner (upper and lower inner quadrants) zones of the breast. Clinical and demographic variables were obtained. Unadjusted survival differences were examined with Kaplan- Meier method. Multivariate Cox regression model was employed to examine the association between zone group and survival.
Results: 125,800 patients were identified including 83,558 (66.4%), 6,764 (5.4%), and 35,449 (28.2%) patients within the outer, central, and inner zones. There was evidence of a difference in age and tumor size based on site (P<0.001). It was also found that there was an association between tumor zone and each of the following (P<0.05): race and ethnicity, Charlson-Deyo score, insurance, income, education, facility type, laterality, histology, utilization of chemotherapy, ER status, PR status, and HER2 status. There was no relationship between site and unadjusted survival (P=0.905). After adjusting for all else, a 5.7% decreased the risk of death was found upon the comparison of the outer vs. inner zone of the breast (95% CI: 0.4%-11.8%; P=0.037). In general, older African American Medicaid patients with increased Charlson-Deyo scores and hormone receptor-negative breast cancers from lower-income areas had decreased survival.
Conclusion: Outer zone breast cancer has a more favorable survival advantage when compared with inner zone cancers. A finding that warrants re-evaluation of the management approach to inner zone breast cancer.
Decreasing Chemotherapy Administration Wait Time for Veterans with Cancer: A Minneapolis VA Medical Center Quality Improvement Project
Background: Cancer diagnosis is a devastating and painful process for patients and their families, resulting in significant stress and uncertainty. Chemotherapy treatments may provide a cure, control or palliate symptoms caused by cancer. However, delivery of chemotherapy in outpatient clinics is challenging and timeconsuming. Long wait is a common patient complaint, affects work-flow and chair time usage, increases costs, and compromises safety. We sought to review our system and implement changes that may result in decrease wait time.
Methods: Utilizing the Institute for Healthcare Improvement (IHI) model, the plan-do-study-act (PDSA) method to test and implement changes, we established a preintervention Ishikawa diagram over a 4 weeks period to study the process and determine cause of delay. Changes were implemented in a stepwise fashion, assess for improvement and revised our process over another 4 week period. We collect and analyze data for a total of 2 months. The objective of the study was to decrease wait-time to initiate chemotherapy treatment from the end of clinic visit to start of chemotherapy infusion by 20-30 minutes for 50% of patients in the oncology clinic over a three-month period.
Results: Pre-intervention data was collected on 245 patients. 55% (n=136) of these patients waited an average of 90 minutes and 45% (n=110) waited an average of 42 minutes from check-in to infusion clinic to start of chemotherapy. Identified barriers causing delayed chemotherapy administration included no consent, no prior authorization, unwritten/unsigned orders, pharmacy release delay, incomplete required labs, delay drug delivery from pharmacy, and difficulty with IV access. After the first cycle of PDSA, post-intervention data reveal a small improvement. 52% (n=199) patients waited an average of 87 minutes and 48% (n=183) average wait was 41 minutes.
Conclusions: By utilizing the PDSA cycle to test the modification of the revised workflow system and eliminate barriers to release of chemotherapy we could potentially reduce wait times for patient receiving chemotherapy at the Minneapolis VA. Updated data will be presented at the AVAHO Annual Meeting.
Background: Cancer diagnosis is a devastating and painful process for patients and their families, resulting in significant stress and uncertainty. Chemotherapy treatments may provide a cure, control or palliate symptoms caused by cancer. However, delivery of chemotherapy in outpatient clinics is challenging and timeconsuming. Long wait is a common patient complaint, affects work-flow and chair time usage, increases costs, and compromises safety. We sought to review our system and implement changes that may result in decrease wait time.
Methods: Utilizing the Institute for Healthcare Improvement (IHI) model, the plan-do-study-act (PDSA) method to test and implement changes, we established a preintervention Ishikawa diagram over a 4 weeks period to study the process and determine cause of delay. Changes were implemented in a stepwise fashion, assess for improvement and revised our process over another 4 week period. We collect and analyze data for a total of 2 months. The objective of the study was to decrease wait-time to initiate chemotherapy treatment from the end of clinic visit to start of chemotherapy infusion by 20-30 minutes for 50% of patients in the oncology clinic over a three-month period.
Results: Pre-intervention data was collected on 245 patients. 55% (n=136) of these patients waited an average of 90 minutes and 45% (n=110) waited an average of 42 minutes from check-in to infusion clinic to start of chemotherapy. Identified barriers causing delayed chemotherapy administration included no consent, no prior authorization, unwritten/unsigned orders, pharmacy release delay, incomplete required labs, delay drug delivery from pharmacy, and difficulty with IV access. After the first cycle of PDSA, post-intervention data reveal a small improvement. 52% (n=199) patients waited an average of 87 minutes and 48% (n=183) average wait was 41 minutes.
Conclusions: By utilizing the PDSA cycle to test the modification of the revised workflow system and eliminate barriers to release of chemotherapy we could potentially reduce wait times for patient receiving chemotherapy at the Minneapolis VA. Updated data will be presented at the AVAHO Annual Meeting.
Background: Cancer diagnosis is a devastating and painful process for patients and their families, resulting in significant stress and uncertainty. Chemotherapy treatments may provide a cure, control or palliate symptoms caused by cancer. However, delivery of chemotherapy in outpatient clinics is challenging and timeconsuming. Long wait is a common patient complaint, affects work-flow and chair time usage, increases costs, and compromises safety. We sought to review our system and implement changes that may result in decrease wait time.
Methods: Utilizing the Institute for Healthcare Improvement (IHI) model, the plan-do-study-act (PDSA) method to test and implement changes, we established a preintervention Ishikawa diagram over a 4 weeks period to study the process and determine cause of delay. Changes were implemented in a stepwise fashion, assess for improvement and revised our process over another 4 week period. We collect and analyze data for a total of 2 months. The objective of the study was to decrease wait-time to initiate chemotherapy treatment from the end of clinic visit to start of chemotherapy infusion by 20-30 minutes for 50% of patients in the oncology clinic over a three-month period.
Results: Pre-intervention data was collected on 245 patients. 55% (n=136) of these patients waited an average of 90 minutes and 45% (n=110) waited an average of 42 minutes from check-in to infusion clinic to start of chemotherapy. Identified barriers causing delayed chemotherapy administration included no consent, no prior authorization, unwritten/unsigned orders, pharmacy release delay, incomplete required labs, delay drug delivery from pharmacy, and difficulty with IV access. After the first cycle of PDSA, post-intervention data reveal a small improvement. 52% (n=199) patients waited an average of 87 minutes and 48% (n=183) average wait was 41 minutes.
Conclusions: By utilizing the PDSA cycle to test the modification of the revised workflow system and eliminate barriers to release of chemotherapy we could potentially reduce wait times for patient receiving chemotherapy at the Minneapolis VA. Updated data will be presented at the AVAHO Annual Meeting.
Identifying Progression-free Survival in Veterans with Diffuse Large B-Cell Lymphoma Using Electronic Health Care Records
Purpose: To establish a gold-standard methodology for accurately extracting progression-free survival (PFS) following Diffuse Large B-Cell Lymphoma (DLBCL) treatment using real-world electronic healthcare record (EHR) data.
Background: Randomized controlled trials using response evaluation criteria have long served as the gold standard for assessing response to therapy and PFS. However, characteristics of participants in clinical trials do not reflect the overall patient population, and formal response evaluation criteria are not used in realworld contexts. Furthermore, real-world data are often unstructured, preventing accurate comparison of PFS using structured clinical trial data versus real-world data, and existing approaches define PFS inconsistently. Despite the importance of assessing PFS in patients outside of controlled clinical trials, no goldstandard method for collecting and validating PFS from real-world evidence has been established.
Methods: Clinicians, programmers, and data scientists collaborated to develop an R Shiny10 application using Veterans Affairs Corporate Data Warehouse data from the EHR of 352 DLBCL patients. The application takes unstructured data such as clinical notes and facilitates the capture, annotation, and tagging of key words or phrases indicative of progression, thus allowing accurate determination of the date of first identification of progression by a treating clinician.
Data Analysis: In order to refine data-collection techniques and evaluate whether the application can enable calculation of real-world PFS, we conducted an adaptive and iterative process of reviewing EHR documents and capturing and annotating data until a consistent schema and methodology was established. In order to validate annotation schema and methodology, annotations of 50 patient records were performed by 2 annotators and assessed for concordance.
Results: We produced an R Shiny application that can capture, annotate, and transform unstructured EHR data into structured data—specifically, treatment lines, cycles, and response criteria with corresponding dates—ready for analysis of PFS. An annotation schema for capturing real-world data was also developed. Mapping of common phrases used by clinicians in real-world practice to response criteria resulted in a dictionary of these phrases.
Implications: These efforts show that it is possible to convert EHR context reliably into analyzable data such as PFS. Further attempts will be made to establish a gold-standard methodology.
Purpose: To establish a gold-standard methodology for accurately extracting progression-free survival (PFS) following Diffuse Large B-Cell Lymphoma (DLBCL) treatment using real-world electronic healthcare record (EHR) data.
Background: Randomized controlled trials using response evaluation criteria have long served as the gold standard for assessing response to therapy and PFS. However, characteristics of participants in clinical trials do not reflect the overall patient population, and formal response evaluation criteria are not used in realworld contexts. Furthermore, real-world data are often unstructured, preventing accurate comparison of PFS using structured clinical trial data versus real-world data, and existing approaches define PFS inconsistently. Despite the importance of assessing PFS in patients outside of controlled clinical trials, no goldstandard method for collecting and validating PFS from real-world evidence has been established.
Methods: Clinicians, programmers, and data scientists collaborated to develop an R Shiny10 application using Veterans Affairs Corporate Data Warehouse data from the EHR of 352 DLBCL patients. The application takes unstructured data such as clinical notes and facilitates the capture, annotation, and tagging of key words or phrases indicative of progression, thus allowing accurate determination of the date of first identification of progression by a treating clinician.
Data Analysis: In order to refine data-collection techniques and evaluate whether the application can enable calculation of real-world PFS, we conducted an adaptive and iterative process of reviewing EHR documents and capturing and annotating data until a consistent schema and methodology was established. In order to validate annotation schema and methodology, annotations of 50 patient records were performed by 2 annotators and assessed for concordance.
Results: We produced an R Shiny application that can capture, annotate, and transform unstructured EHR data into structured data—specifically, treatment lines, cycles, and response criteria with corresponding dates—ready for analysis of PFS. An annotation schema for capturing real-world data was also developed. Mapping of common phrases used by clinicians in real-world practice to response criteria resulted in a dictionary of these phrases.
Implications: These efforts show that it is possible to convert EHR context reliably into analyzable data such as PFS. Further attempts will be made to establish a gold-standard methodology.
Purpose: To establish a gold-standard methodology for accurately extracting progression-free survival (PFS) following Diffuse Large B-Cell Lymphoma (DLBCL) treatment using real-world electronic healthcare record (EHR) data.
Background: Randomized controlled trials using response evaluation criteria have long served as the gold standard for assessing response to therapy and PFS. However, characteristics of participants in clinical trials do not reflect the overall patient population, and formal response evaluation criteria are not used in realworld contexts. Furthermore, real-world data are often unstructured, preventing accurate comparison of PFS using structured clinical trial data versus real-world data, and existing approaches define PFS inconsistently. Despite the importance of assessing PFS in patients outside of controlled clinical trials, no goldstandard method for collecting and validating PFS from real-world evidence has been established.
Methods: Clinicians, programmers, and data scientists collaborated to develop an R Shiny10 application using Veterans Affairs Corporate Data Warehouse data from the EHR of 352 DLBCL patients. The application takes unstructured data such as clinical notes and facilitates the capture, annotation, and tagging of key words or phrases indicative of progression, thus allowing accurate determination of the date of first identification of progression by a treating clinician.
Data Analysis: In order to refine data-collection techniques and evaluate whether the application can enable calculation of real-world PFS, we conducted an adaptive and iterative process of reviewing EHR documents and capturing and annotating data until a consistent schema and methodology was established. In order to validate annotation schema and methodology, annotations of 50 patient records were performed by 2 annotators and assessed for concordance.
Results: We produced an R Shiny application that can capture, annotate, and transform unstructured EHR data into structured data—specifically, treatment lines, cycles, and response criteria with corresponding dates—ready for analysis of PFS. An annotation schema for capturing real-world data was also developed. Mapping of common phrases used by clinicians in real-world practice to response criteria resulted in a dictionary of these phrases.
Implications: These efforts show that it is possible to convert EHR context reliably into analyzable data such as PFS. Further attempts will be made to establish a gold-standard methodology.
The Impact of Using Ideal Body Weight for Dosing of Intravenous Immune Globulin on Potential Grams Averted
Purpose: The primary objective of this study was to evaluate the total potential grams of intravenous immune globulin (IVIG) averted using ideal body weight (IBW) versus actual body weight (ABW) for dosing calculations. The secondary objectives assessed the indication for use of IVIG, change in serum immunoglobulin G (IgG) levels, and potential cost savings of using IBW to dose IVIG as an alternative to ABW.
Background: Dosing of IVIG in clinical studies is based on ABW. Increasing evidence suggests it is more appropriate to dose IVIG using IBW in all patients, given it primarily distributes throughout intravascular and extravascular fluid compartments. Recent studies have demonstrated benefit for the use of IBW for IVIG dosing in regard to outcomes such as grams of drug averted, guideline compliance, and changes in serum IgG levels. This study aimed to add to the body of literature supporting use of IBW for dosing of IVIG.
Methods: A retrospective chart review was conducted for patients administered IVIG therapy between May 1, 2018 and November 30, 2018. IBW was calculated per patient using the Devine equation.
Data Anaysis: Descriptive statistics were used to assess all primary and secondary objectives. This included examining medians and interquartile ranges for the primary objective as well as potential cost savings per dose.
Results: In regard to the primary objective, the total potential grams of IVIG averted was 965 grams. In terms per dose, a median of 45 grams of IVIG per patient could have been averted, with a range from 0 to 75 grams. In regard to secondary objectives, the total potential cost savings was $41,038.57. In terms per dose, a median of $252.43 per patient could have been avoided, with a range from 0 to $634.51. IVIG was most commonly being prescribed for primary humoral immunodeficiency states and chronic lymphocytic leukemia.
Implications: This data may help guide the decision to transition to utilization of IBW for IVIG dosing. In addition, it may give further insight regarding the need to create a pharmacy-to-dose protocol for IVIG.
Purpose: The primary objective of this study was to evaluate the total potential grams of intravenous immune globulin (IVIG) averted using ideal body weight (IBW) versus actual body weight (ABW) for dosing calculations. The secondary objectives assessed the indication for use of IVIG, change in serum immunoglobulin G (IgG) levels, and potential cost savings of using IBW to dose IVIG as an alternative to ABW.
Background: Dosing of IVIG in clinical studies is based on ABW. Increasing evidence suggests it is more appropriate to dose IVIG using IBW in all patients, given it primarily distributes throughout intravascular and extravascular fluid compartments. Recent studies have demonstrated benefit for the use of IBW for IVIG dosing in regard to outcomes such as grams of drug averted, guideline compliance, and changes in serum IgG levels. This study aimed to add to the body of literature supporting use of IBW for dosing of IVIG.
Methods: A retrospective chart review was conducted for patients administered IVIG therapy between May 1, 2018 and November 30, 2018. IBW was calculated per patient using the Devine equation.
Data Anaysis: Descriptive statistics were used to assess all primary and secondary objectives. This included examining medians and interquartile ranges for the primary objective as well as potential cost savings per dose.
Results: In regard to the primary objective, the total potential grams of IVIG averted was 965 grams. In terms per dose, a median of 45 grams of IVIG per patient could have been averted, with a range from 0 to 75 grams. In regard to secondary objectives, the total potential cost savings was $41,038.57. In terms per dose, a median of $252.43 per patient could have been avoided, with a range from 0 to $634.51. IVIG was most commonly being prescribed for primary humoral immunodeficiency states and chronic lymphocytic leukemia.
Implications: This data may help guide the decision to transition to utilization of IBW for IVIG dosing. In addition, it may give further insight regarding the need to create a pharmacy-to-dose protocol for IVIG.
Purpose: The primary objective of this study was to evaluate the total potential grams of intravenous immune globulin (IVIG) averted using ideal body weight (IBW) versus actual body weight (ABW) for dosing calculations. The secondary objectives assessed the indication for use of IVIG, change in serum immunoglobulin G (IgG) levels, and potential cost savings of using IBW to dose IVIG as an alternative to ABW.
Background: Dosing of IVIG in clinical studies is based on ABW. Increasing evidence suggests it is more appropriate to dose IVIG using IBW in all patients, given it primarily distributes throughout intravascular and extravascular fluid compartments. Recent studies have demonstrated benefit for the use of IBW for IVIG dosing in regard to outcomes such as grams of drug averted, guideline compliance, and changes in serum IgG levels. This study aimed to add to the body of literature supporting use of IBW for dosing of IVIG.
Methods: A retrospective chart review was conducted for patients administered IVIG therapy between May 1, 2018 and November 30, 2018. IBW was calculated per patient using the Devine equation.
Data Anaysis: Descriptive statistics were used to assess all primary and secondary objectives. This included examining medians and interquartile ranges for the primary objective as well as potential cost savings per dose.
Results: In regard to the primary objective, the total potential grams of IVIG averted was 965 grams. In terms per dose, a median of 45 grams of IVIG per patient could have been averted, with a range from 0 to 75 grams. In regard to secondary objectives, the total potential cost savings was $41,038.57. In terms per dose, a median of $252.43 per patient could have been avoided, with a range from 0 to $634.51. IVIG was most commonly being prescribed for primary humoral immunodeficiency states and chronic lymphocytic leukemia.
Implications: This data may help guide the decision to transition to utilization of IBW for IVIG dosing. In addition, it may give further insight regarding the need to create a pharmacy-to-dose protocol for IVIG.