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IASLC survey: Ongoing and intensified molecular testing education needed globally
BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.
Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.
The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.
Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.
The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.
“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.
The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.
“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.
When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.
“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.
The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.
BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.
Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.
The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.
Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.
The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.
“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.
The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.
“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.
When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.
“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.
The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.
BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.
Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.
The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.
Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.
The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.
“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.
The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.
“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.
When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.
“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.
The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.
REPORTING FROM WCLC 2019
New IASLC declaration targets tobacco use among cancer patients
BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).
Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.
“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.
Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.
“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.
The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.
In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:
- Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
- Smoking cessation counseling and treatment should be a reimbursable service.
- Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
- Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.
Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.
BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).
Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.
“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.
Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.
“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.
The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.
In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:
- Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
- Smoking cessation counseling and treatment should be a reimbursable service.
- Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
- Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.
Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.
BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).
Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.
“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.
Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.
“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.
The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.
In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:
- Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
- Smoking cessation counseling and treatment should be a reimbursable service.
- Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
- Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.
Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.
REPORTING FROM WCLC 2019
Prostate and Lung Cancer Incidence and Survival Patterns Among Veterans
Background: Prostate cancer (PCa) and lung cancer (LC) are the most common cancers among men, accounting for almost 50% of all cancer cases each year in the Veterans Health Administration (VHA).
Purpose: The objectives of this analysis were to evaluate characteristics and trends in prostate and lung cancer incidence and survival (both overall and cancerspecific) among veterans receiving care in the VHA.
Methods: Data were obtained from the VA Central Cancer Registry for patients diagnosed with prostate or lung cancer. Vital status was obtained from the VA Corporate Data Warehouse and cause of death from the National Death Index. Age-adjusted incidence rates were calculated for patients diagnosed 2005-2014. Rates were based on U.S. 2010 adult population estimates and VHA user population in each fiscal year. All incidence rates are per 100,000 person-years. Fiveyear survival was estimated using the Kaplan-Meier method for patients diagnosed 2002-2012.
Results: For PCa, the age-adjusted incidence 2005- 2014 was 133, with an overall decrease ranging from 161 in 2007 to 94 in 2014. The median age at PCa diagnosis was 65 years, and approximately 86% of patients were diagnosed with clinical stage I/II disease. Five-year overall and PCa-specific survival were 80% and 95%, respectively. Between 2002-2012, overall survival increased from 74% to 82% and PCa-specific survival increased slightly from 93.1% to 94.4%. For LC, the age-adjusted incidence 2005-2014 was 77, with an overall decrease ranging from 88 in 2009 to 62 in 2014. Among males, incidence was 78 and median age at diagnosis was 68 years; corresponding incidence and age among females was 55 and 62 years. Five-year overall survival improved from 10% for 2002 diagnoses to 15% for 2012 diagnoses; similarly, LC-specific survival increased from 16% to 35% during this time.
Implications: Incidence and survival rates for lung and prostate cancer have improved over time in both in VHA, as well as non-veteran specific populations such as the SEER cancer registry, mostly due to advances in cancer detection and treatment options. Evaluating trends and patterns of care can help inform the increasing demand for high-quality cancer care in the VA healthcare system.
Background: Prostate cancer (PCa) and lung cancer (LC) are the most common cancers among men, accounting for almost 50% of all cancer cases each year in the Veterans Health Administration (VHA).
Purpose: The objectives of this analysis were to evaluate characteristics and trends in prostate and lung cancer incidence and survival (both overall and cancerspecific) among veterans receiving care in the VHA.
Methods: Data were obtained from the VA Central Cancer Registry for patients diagnosed with prostate or lung cancer. Vital status was obtained from the VA Corporate Data Warehouse and cause of death from the National Death Index. Age-adjusted incidence rates were calculated for patients diagnosed 2005-2014. Rates were based on U.S. 2010 adult population estimates and VHA user population in each fiscal year. All incidence rates are per 100,000 person-years. Fiveyear survival was estimated using the Kaplan-Meier method for patients diagnosed 2002-2012.
Results: For PCa, the age-adjusted incidence 2005- 2014 was 133, with an overall decrease ranging from 161 in 2007 to 94 in 2014. The median age at PCa diagnosis was 65 years, and approximately 86% of patients were diagnosed with clinical stage I/II disease. Five-year overall and PCa-specific survival were 80% and 95%, respectively. Between 2002-2012, overall survival increased from 74% to 82% and PCa-specific survival increased slightly from 93.1% to 94.4%. For LC, the age-adjusted incidence 2005-2014 was 77, with an overall decrease ranging from 88 in 2009 to 62 in 2014. Among males, incidence was 78 and median age at diagnosis was 68 years; corresponding incidence and age among females was 55 and 62 years. Five-year overall survival improved from 10% for 2002 diagnoses to 15% for 2012 diagnoses; similarly, LC-specific survival increased from 16% to 35% during this time.
Implications: Incidence and survival rates for lung and prostate cancer have improved over time in both in VHA, as well as non-veteran specific populations such as the SEER cancer registry, mostly due to advances in cancer detection and treatment options. Evaluating trends and patterns of care can help inform the increasing demand for high-quality cancer care in the VA healthcare system.
Background: Prostate cancer (PCa) and lung cancer (LC) are the most common cancers among men, accounting for almost 50% of all cancer cases each year in the Veterans Health Administration (VHA).
Purpose: The objectives of this analysis were to evaluate characteristics and trends in prostate and lung cancer incidence and survival (both overall and cancerspecific) among veterans receiving care in the VHA.
Methods: Data were obtained from the VA Central Cancer Registry for patients diagnosed with prostate or lung cancer. Vital status was obtained from the VA Corporate Data Warehouse and cause of death from the National Death Index. Age-adjusted incidence rates were calculated for patients diagnosed 2005-2014. Rates were based on U.S. 2010 adult population estimates and VHA user population in each fiscal year. All incidence rates are per 100,000 person-years. Fiveyear survival was estimated using the Kaplan-Meier method for patients diagnosed 2002-2012.
Results: For PCa, the age-adjusted incidence 2005- 2014 was 133, with an overall decrease ranging from 161 in 2007 to 94 in 2014. The median age at PCa diagnosis was 65 years, and approximately 86% of patients were diagnosed with clinical stage I/II disease. Five-year overall and PCa-specific survival were 80% and 95%, respectively. Between 2002-2012, overall survival increased from 74% to 82% and PCa-specific survival increased slightly from 93.1% to 94.4%. For LC, the age-adjusted incidence 2005-2014 was 77, with an overall decrease ranging from 88 in 2009 to 62 in 2014. Among males, incidence was 78 and median age at diagnosis was 68 years; corresponding incidence and age among females was 55 and 62 years. Five-year overall survival improved from 10% for 2002 diagnoses to 15% for 2012 diagnoses; similarly, LC-specific survival increased from 16% to 35% during this time.
Implications: Incidence and survival rates for lung and prostate cancer have improved over time in both in VHA, as well as non-veteran specific populations such as the SEER cancer registry, mostly due to advances in cancer detection and treatment options. Evaluating trends and patterns of care can help inform the increasing demand for high-quality cancer care in the VA healthcare system.
Guideline-Concordance With Durvalumab in Stage 3 Non-Small Cell Lung Cancer: A Single Institution Experience
Background: Durvalumab is a category 1 recommendation per National Comprehensive Cancer Network (NCCN) guidelines for patients with unresectable Stage III non-small cell lung cancer (NSCLC) following concurrent platinum-based chemotherapy and radiation therapy (CRT). Evidence-based guidelines provide guidance to providers and can improve patient survival across several cancer types. Concordance rates with guidelines have been variable across health institutions. We aim to study the adherence and identify barriers to concordance with Durvalumab usage at our center (Plan).
Methods: This is a retrospective analysis using a QI framework to develop potential process changes for guidelines concordance. All veterans with newly diagnosed stage III unresectable NSCLC seen at the Birmingham VA from October 2017 to the present were reviewed. (Do) Data including demographics, dates of diagnosis and CRT completion, Durvalumab usage and reasons for not prescribing durvalumab were collected.
Results: Forty-two patients with stage III lung cancer were identified between October 2017 and April 2019. Thirty-five patients were evaluable. Twenty out of these patients received concurrent CRT. While 50% of eligible patients (those that had CRT) received Durvalumab only 28% percent of the initial cohort with stage III lung cancer got the therapy. Of the ten eligible patients that did not receive the drug, reasons cited included intolerance to CRT, progression on CRT and refusal by patient. One patient did not have a clearly documented reason for not receiving Durvalumab (Study).
Conclusion: Twenty-eight percent of all stage III lung cancer patients received Durvalumab. However, when looking at patients that completed CRT, usage improved to fifty percent. This discordancy with guidelines is likely explained by the difference between clinical trial populations and real-world populations, though we will work on more aggressive consideration of upfront CRT vs sequential therapy to improve eligibility (Act). In most cases, the reason for the patients not receiving concordant therapy was the listed performance status. Only one patient did not have clear documentation as to why Durvalumab was not given. Our next PDSA cycle will include measures to study reasons for low concordance with focus on patient and system level barriers.
Background: Durvalumab is a category 1 recommendation per National Comprehensive Cancer Network (NCCN) guidelines for patients with unresectable Stage III non-small cell lung cancer (NSCLC) following concurrent platinum-based chemotherapy and radiation therapy (CRT). Evidence-based guidelines provide guidance to providers and can improve patient survival across several cancer types. Concordance rates with guidelines have been variable across health institutions. We aim to study the adherence and identify barriers to concordance with Durvalumab usage at our center (Plan).
Methods: This is a retrospective analysis using a QI framework to develop potential process changes for guidelines concordance. All veterans with newly diagnosed stage III unresectable NSCLC seen at the Birmingham VA from October 2017 to the present were reviewed. (Do) Data including demographics, dates of diagnosis and CRT completion, Durvalumab usage and reasons for not prescribing durvalumab were collected.
Results: Forty-two patients with stage III lung cancer were identified between October 2017 and April 2019. Thirty-five patients were evaluable. Twenty out of these patients received concurrent CRT. While 50% of eligible patients (those that had CRT) received Durvalumab only 28% percent of the initial cohort with stage III lung cancer got the therapy. Of the ten eligible patients that did not receive the drug, reasons cited included intolerance to CRT, progression on CRT and refusal by patient. One patient did not have a clearly documented reason for not receiving Durvalumab (Study).
Conclusion: Twenty-eight percent of all stage III lung cancer patients received Durvalumab. However, when looking at patients that completed CRT, usage improved to fifty percent. This discordancy with guidelines is likely explained by the difference between clinical trial populations and real-world populations, though we will work on more aggressive consideration of upfront CRT vs sequential therapy to improve eligibility (Act). In most cases, the reason for the patients not receiving concordant therapy was the listed performance status. Only one patient did not have clear documentation as to why Durvalumab was not given. Our next PDSA cycle will include measures to study reasons for low concordance with focus on patient and system level barriers.
Background: Durvalumab is a category 1 recommendation per National Comprehensive Cancer Network (NCCN) guidelines for patients with unresectable Stage III non-small cell lung cancer (NSCLC) following concurrent platinum-based chemotherapy and radiation therapy (CRT). Evidence-based guidelines provide guidance to providers and can improve patient survival across several cancer types. Concordance rates with guidelines have been variable across health institutions. We aim to study the adherence and identify barriers to concordance with Durvalumab usage at our center (Plan).
Methods: This is a retrospective analysis using a QI framework to develop potential process changes for guidelines concordance. All veterans with newly diagnosed stage III unresectable NSCLC seen at the Birmingham VA from October 2017 to the present were reviewed. (Do) Data including demographics, dates of diagnosis and CRT completion, Durvalumab usage and reasons for not prescribing durvalumab were collected.
Results: Forty-two patients with stage III lung cancer were identified between October 2017 and April 2019. Thirty-five patients were evaluable. Twenty out of these patients received concurrent CRT. While 50% of eligible patients (those that had CRT) received Durvalumab only 28% percent of the initial cohort with stage III lung cancer got the therapy. Of the ten eligible patients that did not receive the drug, reasons cited included intolerance to CRT, progression on CRT and refusal by patient. One patient did not have a clearly documented reason for not receiving Durvalumab (Study).
Conclusion: Twenty-eight percent of all stage III lung cancer patients received Durvalumab. However, when looking at patients that completed CRT, usage improved to fifty percent. This discordancy with guidelines is likely explained by the difference between clinical trial populations and real-world populations, though we will work on more aggressive consideration of upfront CRT vs sequential therapy to improve eligibility (Act). In most cases, the reason for the patients not receiving concordant therapy was the listed performance status. Only one patient did not have clear documentation as to why Durvalumab was not given. Our next PDSA cycle will include measures to study reasons for low concordance with focus on patient and system level barriers.
Patients With Stage I NSCLC Who Are Not Treated with Either Surgical Resection or Radiation Therapy
Purpose: Approximately 10% of patients with stage I non-small cell lung cancer (NSCLC) are managed without definitive therapy. We therefore investigated whether this rate is similar among veterans cared for by the Veterans Health Administration (VHA), and explored the outcomes and factors associated with under- utilization of these standard of care management strategies.
Methods: The Veterans Affairs (VA) Corporate Data Warehouse (CDW) was queried for all patients diagnosed with NSCLC between 2003 and 2016. Receipt of definitive therapy was determined using VHA cancer registry data, CPT codes and ICD-9/ICD-10 procedure codes within a year after diagnosis. We also captured receipt of chemotherapy as the primary course of treatment, whenever this was the case. Vital status data were assessed using the Kaplan-Meier method.
Results: A total of 19,971 veterans were diagnosed with biopsy-proven clinical stage I NSCLC. The primary treatment for 13,080 (65.5%), 4,889 (24.5%), and 2,002 (10.0%) patients was surgery, RT, or no documented surgery or RT, respectively. The 5-year overall survival for these 3 groups was 53.1%, 19.7%, and 8.9%, respectively. The proportion of patients without documentation of definitive therapy was highest in 2004 at 16.9%, decreasing to 6.3% by 2016. Patients treated at a VA medical center with an on-site radiation oncology service were more likely to receive definitive therapy (chi-square P<0.01). However, this difference was driven by higher utilization of surgery instead of radiation therapy. Among patients without documentation of definitive therapy, 17.4% received systemic chemotherapy as their first reported treatment course.
Conclusion: The proportion of patients without documentation of definitive surgery or RT was similar to previous publications. The rate of no definitive therapy has declined by more than 50% over the past decade, and is coincident with the increased availability of onsite radiotherapy services, as well as minimally invasive thoracic surgery and stereotactic radiotherapy within and outside the VHA. Future investigations of this dataset are likely to increase our understanding about the reasons for treatment delay or avoidance, and its consequences for patients with a highly curable stage I NSCLC.
Purpose: Approximately 10% of patients with stage I non-small cell lung cancer (NSCLC) are managed without definitive therapy. We therefore investigated whether this rate is similar among veterans cared for by the Veterans Health Administration (VHA), and explored the outcomes and factors associated with under- utilization of these standard of care management strategies.
Methods: The Veterans Affairs (VA) Corporate Data Warehouse (CDW) was queried for all patients diagnosed with NSCLC between 2003 and 2016. Receipt of definitive therapy was determined using VHA cancer registry data, CPT codes and ICD-9/ICD-10 procedure codes within a year after diagnosis. We also captured receipt of chemotherapy as the primary course of treatment, whenever this was the case. Vital status data were assessed using the Kaplan-Meier method.
Results: A total of 19,971 veterans were diagnosed with biopsy-proven clinical stage I NSCLC. The primary treatment for 13,080 (65.5%), 4,889 (24.5%), and 2,002 (10.0%) patients was surgery, RT, or no documented surgery or RT, respectively. The 5-year overall survival for these 3 groups was 53.1%, 19.7%, and 8.9%, respectively. The proportion of patients without documentation of definitive therapy was highest in 2004 at 16.9%, decreasing to 6.3% by 2016. Patients treated at a VA medical center with an on-site radiation oncology service were more likely to receive definitive therapy (chi-square P<0.01). However, this difference was driven by higher utilization of surgery instead of radiation therapy. Among patients without documentation of definitive therapy, 17.4% received systemic chemotherapy as their first reported treatment course.
Conclusion: The proportion of patients without documentation of definitive surgery or RT was similar to previous publications. The rate of no definitive therapy has declined by more than 50% over the past decade, and is coincident with the increased availability of onsite radiotherapy services, as well as minimally invasive thoracic surgery and stereotactic radiotherapy within and outside the VHA. Future investigations of this dataset are likely to increase our understanding about the reasons for treatment delay or avoidance, and its consequences for patients with a highly curable stage I NSCLC.
Purpose: Approximately 10% of patients with stage I non-small cell lung cancer (NSCLC) are managed without definitive therapy. We therefore investigated whether this rate is similar among veterans cared for by the Veterans Health Administration (VHA), and explored the outcomes and factors associated with under- utilization of these standard of care management strategies.
Methods: The Veterans Affairs (VA) Corporate Data Warehouse (CDW) was queried for all patients diagnosed with NSCLC between 2003 and 2016. Receipt of definitive therapy was determined using VHA cancer registry data, CPT codes and ICD-9/ICD-10 procedure codes within a year after diagnosis. We also captured receipt of chemotherapy as the primary course of treatment, whenever this was the case. Vital status data were assessed using the Kaplan-Meier method.
Results: A total of 19,971 veterans were diagnosed with biopsy-proven clinical stage I NSCLC. The primary treatment for 13,080 (65.5%), 4,889 (24.5%), and 2,002 (10.0%) patients was surgery, RT, or no documented surgery or RT, respectively. The 5-year overall survival for these 3 groups was 53.1%, 19.7%, and 8.9%, respectively. The proportion of patients without documentation of definitive therapy was highest in 2004 at 16.9%, decreasing to 6.3% by 2016. Patients treated at a VA medical center with an on-site radiation oncology service were more likely to receive definitive therapy (chi-square P<0.01). However, this difference was driven by higher utilization of surgery instead of radiation therapy. Among patients without documentation of definitive therapy, 17.4% received systemic chemotherapy as their first reported treatment course.
Conclusion: The proportion of patients without documentation of definitive surgery or RT was similar to previous publications. The rate of no definitive therapy has declined by more than 50% over the past decade, and is coincident with the increased availability of onsite radiotherapy services, as well as minimally invasive thoracic surgery and stereotactic radiotherapy within and outside the VHA. Future investigations of this dataset are likely to increase our understanding about the reasons for treatment delay or avoidance, and its consequences for patients with a highly curable stage I NSCLC.
Low-Dose Screening CT for Lung Cancer in Selected High-Risk Veterans with a Significant Smoking History: The Providence VA’s Experience
Background: In the US, Lung cancer is the second most common malignancy, but the most common cause of cancer deaths. In 2010, the National Lung Screening Trial described a 20.3% reduction in lung cancer mortality in high-risk patients screened by low-dose spiral CT (LDCT). In 2012, multiple groups established screening guidelines. The National Comprehensive Cancer Network recommended yearly screening for patients aged 55 to 75 years, ≥30 packyears of smoking, or smoking cessation within 15 years. In late 2013, LDCT screening for lung cancer was initiated at the Providence VA Medical Center. It was anticipated that over time there would be a rise in early stage cancers and decrease in late stage cancers. We submitted preliminary data at AVAHO in 2015 with increased earlier detection as anticipated. We have now completed 5 years of screening and are presenting data from 2014 through 2018.
Results: The number of screening CTs has increased almost every year (1929, 1875, 1916, 2201, 2336 respectively), and the number with cancer decreased from 1.34% (2014) to 0.008% (2018). The majority of NSCLCs found have been early stage, but with Small Cell Lung Cancer, 50% had limited and 50% extensive disease. Yearly screening is not likely to increase early detection of Small Cell Lung Cancer. Percentages of stage I & II for NSCLC prior to screening were 30% and 27% in 2012 and 2013 respectively. In 2014 – 2018 percentages were 69%, 60%, 50%, 83% and 50%. In 2016 and 2018, several veterans came to the VA to establish care with a known nodule, or had their first screening CT here, and they were found to have late stage disease. When we subtracted those first time screens the percentages of stage I & II were 69%, 60%, 78%, 83%, and 56%.
Discussion: As expected, for NSCLC yearly LDCT screening increased “pickup” of early stage disease. Unanswered questions include: How long should annual screening continue; What is the financial, emotional and radiation exposure impact of frequent screening, especially for those who need to be followed at more frequent intervals.
Background: In the US, Lung cancer is the second most common malignancy, but the most common cause of cancer deaths. In 2010, the National Lung Screening Trial described a 20.3% reduction in lung cancer mortality in high-risk patients screened by low-dose spiral CT (LDCT). In 2012, multiple groups established screening guidelines. The National Comprehensive Cancer Network recommended yearly screening for patients aged 55 to 75 years, ≥30 packyears of smoking, or smoking cessation within 15 years. In late 2013, LDCT screening for lung cancer was initiated at the Providence VA Medical Center. It was anticipated that over time there would be a rise in early stage cancers and decrease in late stage cancers. We submitted preliminary data at AVAHO in 2015 with increased earlier detection as anticipated. We have now completed 5 years of screening and are presenting data from 2014 through 2018.
Results: The number of screening CTs has increased almost every year (1929, 1875, 1916, 2201, 2336 respectively), and the number with cancer decreased from 1.34% (2014) to 0.008% (2018). The majority of NSCLCs found have been early stage, but with Small Cell Lung Cancer, 50% had limited and 50% extensive disease. Yearly screening is not likely to increase early detection of Small Cell Lung Cancer. Percentages of stage I & II for NSCLC prior to screening were 30% and 27% in 2012 and 2013 respectively. In 2014 – 2018 percentages were 69%, 60%, 50%, 83% and 50%. In 2016 and 2018, several veterans came to the VA to establish care with a known nodule, or had their first screening CT here, and they were found to have late stage disease. When we subtracted those first time screens the percentages of stage I & II were 69%, 60%, 78%, 83%, and 56%.
Discussion: As expected, for NSCLC yearly LDCT screening increased “pickup” of early stage disease. Unanswered questions include: How long should annual screening continue; What is the financial, emotional and radiation exposure impact of frequent screening, especially for those who need to be followed at more frequent intervals.
Background: In the US, Lung cancer is the second most common malignancy, but the most common cause of cancer deaths. In 2010, the National Lung Screening Trial described a 20.3% reduction in lung cancer mortality in high-risk patients screened by low-dose spiral CT (LDCT). In 2012, multiple groups established screening guidelines. The National Comprehensive Cancer Network recommended yearly screening for patients aged 55 to 75 years, ≥30 packyears of smoking, or smoking cessation within 15 years. In late 2013, LDCT screening for lung cancer was initiated at the Providence VA Medical Center. It was anticipated that over time there would be a rise in early stage cancers and decrease in late stage cancers. We submitted preliminary data at AVAHO in 2015 with increased earlier detection as anticipated. We have now completed 5 years of screening and are presenting data from 2014 through 2018.
Results: The number of screening CTs has increased almost every year (1929, 1875, 1916, 2201, 2336 respectively), and the number with cancer decreased from 1.34% (2014) to 0.008% (2018). The majority of NSCLCs found have been early stage, but with Small Cell Lung Cancer, 50% had limited and 50% extensive disease. Yearly screening is not likely to increase early detection of Small Cell Lung Cancer. Percentages of stage I & II for NSCLC prior to screening were 30% and 27% in 2012 and 2013 respectively. In 2014 – 2018 percentages were 69%, 60%, 50%, 83% and 50%. In 2016 and 2018, several veterans came to the VA to establish care with a known nodule, or had their first screening CT here, and they were found to have late stage disease. When we subtracted those first time screens the percentages of stage I & II were 69%, 60%, 78%, 83%, and 56%.
Discussion: As expected, for NSCLC yearly LDCT screening increased “pickup” of early stage disease. Unanswered questions include: How long should annual screening continue; What is the financial, emotional and radiation exposure impact of frequent screening, especially for those who need to be followed at more frequent intervals.
HER2-mutant NSCLC confers high brain metastases risk
Although only a small percentage of non–small cell lung cancers are positive for HER2 mutations, HER2-mutant lung cancers are associated with a high incidence of brain metastases, investigators have found.
Among 98 consecutive patients with HER2-mutant non–small cell lung cancer (NSCLC), the incidence of brain metastases at initial diagnosis was comparable with or slightly lower than that seen with other, more common mutations, but the incidence during treatment was significantly higher than in patients with KRAS-mutant NSCLC, and trended higher than the incidence rate of brain metastases in patients with epidermal growth factor receptor (EGFR)–mutated NSCLC, reported Michael Offin, MD, and colleagues from Memorial Sloan Kettering Cancer in New York.
“This finding provides a framework for CNS surveillance and treatment strategies, including radiotherapy, for patients with HER2-mutant lung cancers and underlines the urgent need for the development of novel HER2-targeted agents with activity in the CNS,” they wrote in Cancer.
NSCLC with oncogenic driver mutations in HER2 account for 2% of adenocarcinomas of the lung, but relatively little is known about the risk for brain metastases in patients HER2-mutant lung cancer, the authors wrote.
“Because HER2-amplified breast cancers are more likely to develop brain metastases through constitutive HER2 signaling, we hypothesize that HER2-mutant lung cancers are also more apt to develop brain metastases in comparison with lung cancers driven by other oncogenes,” they wrote.
To explore this hypothesis, they conducted a retrospective record review of 98 patients treated at their center with metastatic HER2-mutant NSCLC, and compared them with 200 patients with metastatic KRAS-mutant NSCLC, and 200 with metastatic, sensitizing EGFR-mutant NSCLC.
They found that at the initial diagnosis of metastatic disease, the percentage of patients with brain metastases was similar between patients with HER2 mutations and those with KRAS mutations (19% vs. 24%; odds ratio for HER2 vs. KRAS, 0.7; P = .33). However significantly more patients with EGFR-mutant tumors had brain metastases at diagnosis, compared with patients HER2 mutations (31% vs. 19%; OR, 0.5; P = .03).
Interestingly, significantly more patients with HER2-mutant tumors developed brain metastases on treatment than patients with KRAS-mutant tumors (28% vs. 8%; hazard ratio, 5.2; P less than .001). There was also a trend toward more on-treatment brain metastases among patients with HER2 mutations, compared with patients with EGFR mutation (28% vs .16%; HR, 1.7), but this difference was not statistically significant.
The risk for on-treatment brain metastases was even higher among patients with a HER2 mutation characterized by a 12 base–pair, in-frame insertion in exon 20 (HER2 YVMA). In these patients, the OR for brain metastases developing during treatment versus patients with KRAS mutations was 5.9 (P less than .001).
The median overall survival was worse for patients with KRAS-mutant NSCLC (1.1 years) and HER2-mutant cancers (1.6 years) versus 3 years for patients with EFGR-mutant cancers (P less than .001 for KRAS; P = .002 for HER2 vs. EGFR).
The use of HER2-targeted therapies did not have an effect on either the development of brain metastases or survival, and overall survival was slightly but significantly worse for patients with HER2-mutant tumors who had radiotherapy of the brain.
The study was supported by the National Institutes of Health through a National Cancer Institute Cancer Center support grant and by the Eloise Briskin Foundation. Dr. Offin reported honoraria from Bristol-Myers Squibb, Merck, PharmaMar, Novartis, and Targeted Oncology. Multiple coauthors had similar disclosures.
SOURCE: Offin M et al. Cancer. 2019 Aug 30. doi: 10.1002/cncr.32461.
The report by Offin et al. adds to the growing body of literature supporting the potential value of surveillance brain imaging in a subset of patients with lung cancer. The optimal frequency of surveillance brain imaging in patients with non–small cell lung cancer (NSCLC) after the initial diagnosis of metastatic disease has not been established, and practices vary widely. For example, in our own practice, we routinely perform surveillance brain imaging for patients with ALK fusion–positive lung cancer even in the absence of new neurologic symptoms or signs because of a relatively high cumulative incidence of brain metastases within this subgroup in retrospective studies. Whether a similar approach should be taken for HER2-mutant patients awaits further data. Ultimately, in this era of rapidly evolving therapies for advanced NSCLC, early detection of relatively small, asymptomatic brain metastases could translate into the ability to avoid potentially morbid local CNS-directed therapies (such as surgical resection or whole-brain radiotherapy) while allowing the prompt initiation of CNS-active systemic therapies. At the same time, surveillance strategies will need to be data driven and balanced against health utilization considerations and patient preferences.
Overall, the study by Offin et al. offers important new insights into the incidence of brain metastases in HER2-mutant NSCLC. The finding of a relatively high cumulative incidence of brain metastases in this patient population and the shorter survival resulting therein underscore the urgency of developing better HER2-targeted therapeutics with CNS efficacy. Finally, further investigation will be needed to continue to elucidate potential differences in the CNS tropism of distinct oncogenic drivers in NSCLC and to understand the biological mechanisms underlying these differences.
Remarks by Jessica J. Lin, MD, and Justin F. Gainor, MD, from the Massachusetts General Hospital Cancer Center in Boston are adapted and condensed from an editorial accompanying the study by Offin et al. published online in Cancer. No funding source was reported. Dr. Lin reported serving as a compensated consultant for or receiving honoraria from Chugai and Boehringer Ingelheim, and receiving institutional research funding from Loxo Oncology and Novartis. Dr. Gainor has served as a compensated consultant for or received honoraria or research support from numerous pharmaceutical companies and has an immediate family member who is an employee of Ironwood Pharmaceuticals.
The report by Offin et al. adds to the growing body of literature supporting the potential value of surveillance brain imaging in a subset of patients with lung cancer. The optimal frequency of surveillance brain imaging in patients with non–small cell lung cancer (NSCLC) after the initial diagnosis of metastatic disease has not been established, and practices vary widely. For example, in our own practice, we routinely perform surveillance brain imaging for patients with ALK fusion–positive lung cancer even in the absence of new neurologic symptoms or signs because of a relatively high cumulative incidence of brain metastases within this subgroup in retrospective studies. Whether a similar approach should be taken for HER2-mutant patients awaits further data. Ultimately, in this era of rapidly evolving therapies for advanced NSCLC, early detection of relatively small, asymptomatic brain metastases could translate into the ability to avoid potentially morbid local CNS-directed therapies (such as surgical resection or whole-brain radiotherapy) while allowing the prompt initiation of CNS-active systemic therapies. At the same time, surveillance strategies will need to be data driven and balanced against health utilization considerations and patient preferences.
Overall, the study by Offin et al. offers important new insights into the incidence of brain metastases in HER2-mutant NSCLC. The finding of a relatively high cumulative incidence of brain metastases in this patient population and the shorter survival resulting therein underscore the urgency of developing better HER2-targeted therapeutics with CNS efficacy. Finally, further investigation will be needed to continue to elucidate potential differences in the CNS tropism of distinct oncogenic drivers in NSCLC and to understand the biological mechanisms underlying these differences.
Remarks by Jessica J. Lin, MD, and Justin F. Gainor, MD, from the Massachusetts General Hospital Cancer Center in Boston are adapted and condensed from an editorial accompanying the study by Offin et al. published online in Cancer. No funding source was reported. Dr. Lin reported serving as a compensated consultant for or receiving honoraria from Chugai and Boehringer Ingelheim, and receiving institutional research funding from Loxo Oncology and Novartis. Dr. Gainor has served as a compensated consultant for or received honoraria or research support from numerous pharmaceutical companies and has an immediate family member who is an employee of Ironwood Pharmaceuticals.
The report by Offin et al. adds to the growing body of literature supporting the potential value of surveillance brain imaging in a subset of patients with lung cancer. The optimal frequency of surveillance brain imaging in patients with non–small cell lung cancer (NSCLC) after the initial diagnosis of metastatic disease has not been established, and practices vary widely. For example, in our own practice, we routinely perform surveillance brain imaging for patients with ALK fusion–positive lung cancer even in the absence of new neurologic symptoms or signs because of a relatively high cumulative incidence of brain metastases within this subgroup in retrospective studies. Whether a similar approach should be taken for HER2-mutant patients awaits further data. Ultimately, in this era of rapidly evolving therapies for advanced NSCLC, early detection of relatively small, asymptomatic brain metastases could translate into the ability to avoid potentially morbid local CNS-directed therapies (such as surgical resection or whole-brain radiotherapy) while allowing the prompt initiation of CNS-active systemic therapies. At the same time, surveillance strategies will need to be data driven and balanced against health utilization considerations and patient preferences.
Overall, the study by Offin et al. offers important new insights into the incidence of brain metastases in HER2-mutant NSCLC. The finding of a relatively high cumulative incidence of brain metastases in this patient population and the shorter survival resulting therein underscore the urgency of developing better HER2-targeted therapeutics with CNS efficacy. Finally, further investigation will be needed to continue to elucidate potential differences in the CNS tropism of distinct oncogenic drivers in NSCLC and to understand the biological mechanisms underlying these differences.
Remarks by Jessica J. Lin, MD, and Justin F. Gainor, MD, from the Massachusetts General Hospital Cancer Center in Boston are adapted and condensed from an editorial accompanying the study by Offin et al. published online in Cancer. No funding source was reported. Dr. Lin reported serving as a compensated consultant for or receiving honoraria from Chugai and Boehringer Ingelheim, and receiving institutional research funding from Loxo Oncology and Novartis. Dr. Gainor has served as a compensated consultant for or received honoraria or research support from numerous pharmaceutical companies and has an immediate family member who is an employee of Ironwood Pharmaceuticals.
Although only a small percentage of non–small cell lung cancers are positive for HER2 mutations, HER2-mutant lung cancers are associated with a high incidence of brain metastases, investigators have found.
Among 98 consecutive patients with HER2-mutant non–small cell lung cancer (NSCLC), the incidence of brain metastases at initial diagnosis was comparable with or slightly lower than that seen with other, more common mutations, but the incidence during treatment was significantly higher than in patients with KRAS-mutant NSCLC, and trended higher than the incidence rate of brain metastases in patients with epidermal growth factor receptor (EGFR)–mutated NSCLC, reported Michael Offin, MD, and colleagues from Memorial Sloan Kettering Cancer in New York.
“This finding provides a framework for CNS surveillance and treatment strategies, including radiotherapy, for patients with HER2-mutant lung cancers and underlines the urgent need for the development of novel HER2-targeted agents with activity in the CNS,” they wrote in Cancer.
NSCLC with oncogenic driver mutations in HER2 account for 2% of adenocarcinomas of the lung, but relatively little is known about the risk for brain metastases in patients HER2-mutant lung cancer, the authors wrote.
“Because HER2-amplified breast cancers are more likely to develop brain metastases through constitutive HER2 signaling, we hypothesize that HER2-mutant lung cancers are also more apt to develop brain metastases in comparison with lung cancers driven by other oncogenes,” they wrote.
To explore this hypothesis, they conducted a retrospective record review of 98 patients treated at their center with metastatic HER2-mutant NSCLC, and compared them with 200 patients with metastatic KRAS-mutant NSCLC, and 200 with metastatic, sensitizing EGFR-mutant NSCLC.
They found that at the initial diagnosis of metastatic disease, the percentage of patients with brain metastases was similar between patients with HER2 mutations and those with KRAS mutations (19% vs. 24%; odds ratio for HER2 vs. KRAS, 0.7; P = .33). However significantly more patients with EGFR-mutant tumors had brain metastases at diagnosis, compared with patients HER2 mutations (31% vs. 19%; OR, 0.5; P = .03).
Interestingly, significantly more patients with HER2-mutant tumors developed brain metastases on treatment than patients with KRAS-mutant tumors (28% vs. 8%; hazard ratio, 5.2; P less than .001). There was also a trend toward more on-treatment brain metastases among patients with HER2 mutations, compared with patients with EGFR mutation (28% vs .16%; HR, 1.7), but this difference was not statistically significant.
The risk for on-treatment brain metastases was even higher among patients with a HER2 mutation characterized by a 12 base–pair, in-frame insertion in exon 20 (HER2 YVMA). In these patients, the OR for brain metastases developing during treatment versus patients with KRAS mutations was 5.9 (P less than .001).
The median overall survival was worse for patients with KRAS-mutant NSCLC (1.1 years) and HER2-mutant cancers (1.6 years) versus 3 years for patients with EFGR-mutant cancers (P less than .001 for KRAS; P = .002 for HER2 vs. EGFR).
The use of HER2-targeted therapies did not have an effect on either the development of brain metastases or survival, and overall survival was slightly but significantly worse for patients with HER2-mutant tumors who had radiotherapy of the brain.
The study was supported by the National Institutes of Health through a National Cancer Institute Cancer Center support grant and by the Eloise Briskin Foundation. Dr. Offin reported honoraria from Bristol-Myers Squibb, Merck, PharmaMar, Novartis, and Targeted Oncology. Multiple coauthors had similar disclosures.
SOURCE: Offin M et al. Cancer. 2019 Aug 30. doi: 10.1002/cncr.32461.
Although only a small percentage of non–small cell lung cancers are positive for HER2 mutations, HER2-mutant lung cancers are associated with a high incidence of brain metastases, investigators have found.
Among 98 consecutive patients with HER2-mutant non–small cell lung cancer (NSCLC), the incidence of brain metastases at initial diagnosis was comparable with or slightly lower than that seen with other, more common mutations, but the incidence during treatment was significantly higher than in patients with KRAS-mutant NSCLC, and trended higher than the incidence rate of brain metastases in patients with epidermal growth factor receptor (EGFR)–mutated NSCLC, reported Michael Offin, MD, and colleagues from Memorial Sloan Kettering Cancer in New York.
“This finding provides a framework for CNS surveillance and treatment strategies, including radiotherapy, for patients with HER2-mutant lung cancers and underlines the urgent need for the development of novel HER2-targeted agents with activity in the CNS,” they wrote in Cancer.
NSCLC with oncogenic driver mutations in HER2 account for 2% of adenocarcinomas of the lung, but relatively little is known about the risk for brain metastases in patients HER2-mutant lung cancer, the authors wrote.
“Because HER2-amplified breast cancers are more likely to develop brain metastases through constitutive HER2 signaling, we hypothesize that HER2-mutant lung cancers are also more apt to develop brain metastases in comparison with lung cancers driven by other oncogenes,” they wrote.
To explore this hypothesis, they conducted a retrospective record review of 98 patients treated at their center with metastatic HER2-mutant NSCLC, and compared them with 200 patients with metastatic KRAS-mutant NSCLC, and 200 with metastatic, sensitizing EGFR-mutant NSCLC.
They found that at the initial diagnosis of metastatic disease, the percentage of patients with brain metastases was similar between patients with HER2 mutations and those with KRAS mutations (19% vs. 24%; odds ratio for HER2 vs. KRAS, 0.7; P = .33). However significantly more patients with EGFR-mutant tumors had brain metastases at diagnosis, compared with patients HER2 mutations (31% vs. 19%; OR, 0.5; P = .03).
Interestingly, significantly more patients with HER2-mutant tumors developed brain metastases on treatment than patients with KRAS-mutant tumors (28% vs. 8%; hazard ratio, 5.2; P less than .001). There was also a trend toward more on-treatment brain metastases among patients with HER2 mutations, compared with patients with EGFR mutation (28% vs .16%; HR, 1.7), but this difference was not statistically significant.
The risk for on-treatment brain metastases was even higher among patients with a HER2 mutation characterized by a 12 base–pair, in-frame insertion in exon 20 (HER2 YVMA). In these patients, the OR for brain metastases developing during treatment versus patients with KRAS mutations was 5.9 (P less than .001).
The median overall survival was worse for patients with KRAS-mutant NSCLC (1.1 years) and HER2-mutant cancers (1.6 years) versus 3 years for patients with EFGR-mutant cancers (P less than .001 for KRAS; P = .002 for HER2 vs. EGFR).
The use of HER2-targeted therapies did not have an effect on either the development of brain metastases or survival, and overall survival was slightly but significantly worse for patients with HER2-mutant tumors who had radiotherapy of the brain.
The study was supported by the National Institutes of Health through a National Cancer Institute Cancer Center support grant and by the Eloise Briskin Foundation. Dr. Offin reported honoraria from Bristol-Myers Squibb, Merck, PharmaMar, Novartis, and Targeted Oncology. Multiple coauthors had similar disclosures.
SOURCE: Offin M et al. Cancer. 2019 Aug 30. doi: 10.1002/cncr.32461.
FROM CANCER
Durvalumab-Induced Hyperprogressive Disease in Non-Metastatic Lung Cancer
Background: Immune checkpoint inhibitors (ICI) have tremendously changed the paradigm of management for advanced stage cancers such as lung malignancies. Two unique patterns of response to immunotherapy have recently been described: pseudoprogression and hyperprogression. Hyperprogression is defined as a 2-fold increase in the tumor growth rate within 8 weeks of ICI administration.
Case Presentation: A 58-year-old female presented with left-sided chest pain for two weeks. CT-chest with contrast showed an 8.6 × 6.1 × 7.6 cm3 left upper lobe mass. An endobronchial ultrasound (EBUS)-guided biopsy revealed poorly differentiated adenocarcinoma. Staging FDG-18 PET scan revealed no metastases, resulting in a stage IIIA Non-Small Cell Lung Cancer (T4N0M0) on presentation. Per NCCN guidelines, she received standard of care definitive concurrent chemoradiation. Follow-up scans showed significant response in local disease without distant metastases. The patient then received cycle 1 consolidation immunotherapy with Durvalumab. Two weeks after, she complained of fatigue, new-onset headache and worsening dyspnea. CT-chest revealed development of a right upper lobe opacity, MRI brain showed the development of multiple brain metastases and PET scan uncovered hypermetabolic activity in a left adrenal nodule. Biopsy of the adrenal nodule confirmed metastatic adenocarcinoma, consistent with hyperprogression. Molecular testing of the standard lung tumor markers was negative (EGFR(-) ALK(-) BRAF(-) ROS-1 (-) PD-L1 <1%). Given her hyperprogression on ICIs, we opted to treat her with systemic chemotherapy with Carboplatin and Pemetrexed.
Conclusion: We herein report the first case report of hyperprogression in the non-metastatic setting. As ICIs become more incorporated in oncology practice, physicians should be aware of hyperprogression and its diagnostic criteria. Current molecular predictors of hyperprogression include MDM2/4 and EGFR mutations. Further elucidation of predictors of hyperprogressive disease will help guide better selection of ICI candidates.
Background: Immune checkpoint inhibitors (ICI) have tremendously changed the paradigm of management for advanced stage cancers such as lung malignancies. Two unique patterns of response to immunotherapy have recently been described: pseudoprogression and hyperprogression. Hyperprogression is defined as a 2-fold increase in the tumor growth rate within 8 weeks of ICI administration.
Case Presentation: A 58-year-old female presented with left-sided chest pain for two weeks. CT-chest with contrast showed an 8.6 × 6.1 × 7.6 cm3 left upper lobe mass. An endobronchial ultrasound (EBUS)-guided biopsy revealed poorly differentiated adenocarcinoma. Staging FDG-18 PET scan revealed no metastases, resulting in a stage IIIA Non-Small Cell Lung Cancer (T4N0M0) on presentation. Per NCCN guidelines, she received standard of care definitive concurrent chemoradiation. Follow-up scans showed significant response in local disease without distant metastases. The patient then received cycle 1 consolidation immunotherapy with Durvalumab. Two weeks after, she complained of fatigue, new-onset headache and worsening dyspnea. CT-chest revealed development of a right upper lobe opacity, MRI brain showed the development of multiple brain metastases and PET scan uncovered hypermetabolic activity in a left adrenal nodule. Biopsy of the adrenal nodule confirmed metastatic adenocarcinoma, consistent with hyperprogression. Molecular testing of the standard lung tumor markers was negative (EGFR(-) ALK(-) BRAF(-) ROS-1 (-) PD-L1 <1%). Given her hyperprogression on ICIs, we opted to treat her with systemic chemotherapy with Carboplatin and Pemetrexed.
Conclusion: We herein report the first case report of hyperprogression in the non-metastatic setting. As ICIs become more incorporated in oncology practice, physicians should be aware of hyperprogression and its diagnostic criteria. Current molecular predictors of hyperprogression include MDM2/4 and EGFR mutations. Further elucidation of predictors of hyperprogressive disease will help guide better selection of ICI candidates.
Background: Immune checkpoint inhibitors (ICI) have tremendously changed the paradigm of management for advanced stage cancers such as lung malignancies. Two unique patterns of response to immunotherapy have recently been described: pseudoprogression and hyperprogression. Hyperprogression is defined as a 2-fold increase in the tumor growth rate within 8 weeks of ICI administration.
Case Presentation: A 58-year-old female presented with left-sided chest pain for two weeks. CT-chest with contrast showed an 8.6 × 6.1 × 7.6 cm3 left upper lobe mass. An endobronchial ultrasound (EBUS)-guided biopsy revealed poorly differentiated adenocarcinoma. Staging FDG-18 PET scan revealed no metastases, resulting in a stage IIIA Non-Small Cell Lung Cancer (T4N0M0) on presentation. Per NCCN guidelines, she received standard of care definitive concurrent chemoradiation. Follow-up scans showed significant response in local disease without distant metastases. The patient then received cycle 1 consolidation immunotherapy with Durvalumab. Two weeks after, she complained of fatigue, new-onset headache and worsening dyspnea. CT-chest revealed development of a right upper lobe opacity, MRI brain showed the development of multiple brain metastases and PET scan uncovered hypermetabolic activity in a left adrenal nodule. Biopsy of the adrenal nodule confirmed metastatic adenocarcinoma, consistent with hyperprogression. Molecular testing of the standard lung tumor markers was negative (EGFR(-) ALK(-) BRAF(-) ROS-1 (-) PD-L1 <1%). Given her hyperprogression on ICIs, we opted to treat her with systemic chemotherapy with Carboplatin and Pemetrexed.
Conclusion: We herein report the first case report of hyperprogression in the non-metastatic setting. As ICIs become more incorporated in oncology practice, physicians should be aware of hyperprogression and its diagnostic criteria. Current molecular predictors of hyperprogression include MDM2/4 and EGFR mutations. Further elucidation of predictors of hyperprogressive disease will help guide better selection of ICI candidates.
Cardiac Tamponade in a Patient with Stage IV Lung Adenocarcinoma Treated with Pembrolizumab
Background: In 2018, a male aged 62 years with a history of squamous cell tonsillar cancer, which was successfully treated by concurrent chemoradiation and selective neck dissection in 2014, was diagnosed with primary right sided lung adenocarcinoma (Stage IV, cT4c cN3 cM1a) after presenting with post-obstructive pneumonia. Molecular analysis was about 100% positive for PDL-1 and negative for EGFR, ALK, BRAF, and ROS. The patient was started on Pembrolizumab. After 5 cycles, he developed worsening dyspnea. A CT scan of his chest revealed a large pericardial effusion and decrease in size of right upper lobe lesion. An echocardiogram confirmed cardiac tamponade physiology. 400 ml of fluid was removed by emergent pericardial window and surgical drain was placed. Cytopathological analysis of pericardial fluid returned negative for malignant cells. The patient was treated with high dose prednisone with tapering, and pembrolizumab was discontinued. Patient responded very well. A repeat CT and ECHO after 3 months of treatment confirmed nearresolution of effusion.
Discussion: Distinguishing immune mediated pericardial effusion from malignant effusion is vital. Development of pericardial effusion with concurrent improvement or stability of malignant lesion, negative cytology and brisk response to corticosteroids indicates an immune etiology.
Pericardiocentesis or pericardial window is the key intervention in acute management. The critical step in immune mediated pericardial effusions is initiation of high-dose corticosteroids (1-2 mg/kg of Prednisone) with tapering of at least 4 weeks in severe cases. In unresponsive cases, corticosteroids at transplant rejection dose (1 g methylprednisone daily) and addition of mycophenolate mofetil, in iximab or antithymocyte globulin should be considered. As per ‘ASCO Practice Guideline’, any grade of cardiotoxicity above grade 1 warrants holding or permanently discontinuing the immunotherapy. For pericardial effusions secondary to pseudoprogression, immunotherapy can be continued.
Based on our literature review, concurrence of other immune related adverse events and recurrence of effusions with discontinuation of corticosteroids is reported with immune mediated pericardial effusions.
Conclusion: Early identification of immune related adverse events is very important. In immune mediated pericardial effusion, pericardial fluid should be drained, and corticosteroids should be started promptly. Permanent discontinuation of immunotherapy is recommended for grade 3 and 4 cardiotoxicity. Re-challenge of immunotherapy after treating the adverse event is a subject that needs further research.
Background: In 2018, a male aged 62 years with a history of squamous cell tonsillar cancer, which was successfully treated by concurrent chemoradiation and selective neck dissection in 2014, was diagnosed with primary right sided lung adenocarcinoma (Stage IV, cT4c cN3 cM1a) after presenting with post-obstructive pneumonia. Molecular analysis was about 100% positive for PDL-1 and negative for EGFR, ALK, BRAF, and ROS. The patient was started on Pembrolizumab. After 5 cycles, he developed worsening dyspnea. A CT scan of his chest revealed a large pericardial effusion and decrease in size of right upper lobe lesion. An echocardiogram confirmed cardiac tamponade physiology. 400 ml of fluid was removed by emergent pericardial window and surgical drain was placed. Cytopathological analysis of pericardial fluid returned negative for malignant cells. The patient was treated with high dose prednisone with tapering, and pembrolizumab was discontinued. Patient responded very well. A repeat CT and ECHO after 3 months of treatment confirmed nearresolution of effusion.
Discussion: Distinguishing immune mediated pericardial effusion from malignant effusion is vital. Development of pericardial effusion with concurrent improvement or stability of malignant lesion, negative cytology and brisk response to corticosteroids indicates an immune etiology.
Pericardiocentesis or pericardial window is the key intervention in acute management. The critical step in immune mediated pericardial effusions is initiation of high-dose corticosteroids (1-2 mg/kg of Prednisone) with tapering of at least 4 weeks in severe cases. In unresponsive cases, corticosteroids at transplant rejection dose (1 g methylprednisone daily) and addition of mycophenolate mofetil, in iximab or antithymocyte globulin should be considered. As per ‘ASCO Practice Guideline’, any grade of cardiotoxicity above grade 1 warrants holding or permanently discontinuing the immunotherapy. For pericardial effusions secondary to pseudoprogression, immunotherapy can be continued.
Based on our literature review, concurrence of other immune related adverse events and recurrence of effusions with discontinuation of corticosteroids is reported with immune mediated pericardial effusions.
Conclusion: Early identification of immune related adverse events is very important. In immune mediated pericardial effusion, pericardial fluid should be drained, and corticosteroids should be started promptly. Permanent discontinuation of immunotherapy is recommended for grade 3 and 4 cardiotoxicity. Re-challenge of immunotherapy after treating the adverse event is a subject that needs further research.
Background: In 2018, a male aged 62 years with a history of squamous cell tonsillar cancer, which was successfully treated by concurrent chemoradiation and selective neck dissection in 2014, was diagnosed with primary right sided lung adenocarcinoma (Stage IV, cT4c cN3 cM1a) after presenting with post-obstructive pneumonia. Molecular analysis was about 100% positive for PDL-1 and negative for EGFR, ALK, BRAF, and ROS. The patient was started on Pembrolizumab. After 5 cycles, he developed worsening dyspnea. A CT scan of his chest revealed a large pericardial effusion and decrease in size of right upper lobe lesion. An echocardiogram confirmed cardiac tamponade physiology. 400 ml of fluid was removed by emergent pericardial window and surgical drain was placed. Cytopathological analysis of pericardial fluid returned negative for malignant cells. The patient was treated with high dose prednisone with tapering, and pembrolizumab was discontinued. Patient responded very well. A repeat CT and ECHO after 3 months of treatment confirmed nearresolution of effusion.
Discussion: Distinguishing immune mediated pericardial effusion from malignant effusion is vital. Development of pericardial effusion with concurrent improvement or stability of malignant lesion, negative cytology and brisk response to corticosteroids indicates an immune etiology.
Pericardiocentesis or pericardial window is the key intervention in acute management. The critical step in immune mediated pericardial effusions is initiation of high-dose corticosteroids (1-2 mg/kg of Prednisone) with tapering of at least 4 weeks in severe cases. In unresponsive cases, corticosteroids at transplant rejection dose (1 g methylprednisone daily) and addition of mycophenolate mofetil, in iximab or antithymocyte globulin should be considered. As per ‘ASCO Practice Guideline’, any grade of cardiotoxicity above grade 1 warrants holding or permanently discontinuing the immunotherapy. For pericardial effusions secondary to pseudoprogression, immunotherapy can be continued.
Based on our literature review, concurrence of other immune related adverse events and recurrence of effusions with discontinuation of corticosteroids is reported with immune mediated pericardial effusions.
Conclusion: Early identification of immune related adverse events is very important. In immune mediated pericardial effusion, pericardial fluid should be drained, and corticosteroids should be started promptly. Permanent discontinuation of immunotherapy is recommended for grade 3 and 4 cardiotoxicity. Re-challenge of immunotherapy after treating the adverse event is a subject that needs further research.
Use of Palliative Radiotherapy for Stage IV Lung Cancer Patients with Thoracic Symptoms in the Veterans Health Administration (VHA)
Background: Palliative radiotherapy plays an important role in metastatic lung cancer (LC) treatment. Of VHA LC patients, 46% present with metastatic disease. The American Society for Radiation Oncology (ASTRO) has developed evidenced-based guidelines regarding management of metastatic LC.
Methods: In May 2016, an electronic survey of 84 VHA Radiation Oncologists (ROs) was conducted to assess metastatic LC management. Information on years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines was obtained. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, preferences for/ against concurrent chemotherapy, and use of endobronchial brachytherapy (EBB) and/or YAG laser technology. Survey results were assessed for concordance with ASTRO guidelines.
Results: The survey response rate was 64%. Among respondents, 96% were board certified, 90% held academic appointments, 85% were full-time employees, 11% were part-time employees, and 3% were employed on contract. When asked about use of palliative radiotherapy for lung cancer, 88% were familiar with ASTRO guidelines, 13% had used Stereotactic Body Radiotherapy (SBRT) for palliation, and 26% referred to outside centers for EBB.
Clinical Scenarios: Case 1 – Metastatic (M1b) disease with local chest wall pain and 3 month life expectancy: All respondents recommended palliative radiotherapy, and most (98%) did not recommend concurrent chemotherapy. The fractionation schemes most often used were 20 Gy in 5 fractions (69%) and 30 Gy in 10 fractions (22%).
Case 2 – Metastatic (M1a) disease with endobronchial tumor blockage: 87% of the respondents would use conventional radiotherapy for symptoms such as hemoptysis, intractable cough, and pain, and the remainder would use SBRT. Almost half of respondents (49%) recommended EBB or YAG lung re-expansion before external beam radiotherapy.
Conclusion: In our study of VHA ROs and their knowledge of management of advanced (M1a/M1b) lung cancer, we found no distinction in clinical decisions based on demographic profiles. Almost all reported knowledge of evidence-based treatment guidelines for palliative radiotherapy of lung cancer and most recommended treatment according to current guidelines.”
Background: Palliative radiotherapy plays an important role in metastatic lung cancer (LC) treatment. Of VHA LC patients, 46% present with metastatic disease. The American Society for Radiation Oncology (ASTRO) has developed evidenced-based guidelines regarding management of metastatic LC.
Methods: In May 2016, an electronic survey of 84 VHA Radiation Oncologists (ROs) was conducted to assess metastatic LC management. Information on years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines was obtained. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, preferences for/ against concurrent chemotherapy, and use of endobronchial brachytherapy (EBB) and/or YAG laser technology. Survey results were assessed for concordance with ASTRO guidelines.
Results: The survey response rate was 64%. Among respondents, 96% were board certified, 90% held academic appointments, 85% were full-time employees, 11% were part-time employees, and 3% were employed on contract. When asked about use of palliative radiotherapy for lung cancer, 88% were familiar with ASTRO guidelines, 13% had used Stereotactic Body Radiotherapy (SBRT) for palliation, and 26% referred to outside centers for EBB.
Clinical Scenarios: Case 1 – Metastatic (M1b) disease with local chest wall pain and 3 month life expectancy: All respondents recommended palliative radiotherapy, and most (98%) did not recommend concurrent chemotherapy. The fractionation schemes most often used were 20 Gy in 5 fractions (69%) and 30 Gy in 10 fractions (22%).
Case 2 – Metastatic (M1a) disease with endobronchial tumor blockage: 87% of the respondents would use conventional radiotherapy for symptoms such as hemoptysis, intractable cough, and pain, and the remainder would use SBRT. Almost half of respondents (49%) recommended EBB or YAG lung re-expansion before external beam radiotherapy.
Conclusion: In our study of VHA ROs and their knowledge of management of advanced (M1a/M1b) lung cancer, we found no distinction in clinical decisions based on demographic profiles. Almost all reported knowledge of evidence-based treatment guidelines for palliative radiotherapy of lung cancer and most recommended treatment according to current guidelines.”
Background: Palliative radiotherapy plays an important role in metastatic lung cancer (LC) treatment. Of VHA LC patients, 46% present with metastatic disease. The American Society for Radiation Oncology (ASTRO) has developed evidenced-based guidelines regarding management of metastatic LC.
Methods: In May 2016, an electronic survey of 84 VHA Radiation Oncologists (ROs) was conducted to assess metastatic LC management. Information on years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines was obtained. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, preferences for/ against concurrent chemotherapy, and use of endobronchial brachytherapy (EBB) and/or YAG laser technology. Survey results were assessed for concordance with ASTRO guidelines.
Results: The survey response rate was 64%. Among respondents, 96% were board certified, 90% held academic appointments, 85% were full-time employees, 11% were part-time employees, and 3% were employed on contract. When asked about use of palliative radiotherapy for lung cancer, 88% were familiar with ASTRO guidelines, 13% had used Stereotactic Body Radiotherapy (SBRT) for palliation, and 26% referred to outside centers for EBB.
Clinical Scenarios: Case 1 – Metastatic (M1b) disease with local chest wall pain and 3 month life expectancy: All respondents recommended palliative radiotherapy, and most (98%) did not recommend concurrent chemotherapy. The fractionation schemes most often used were 20 Gy in 5 fractions (69%) and 30 Gy in 10 fractions (22%).
Case 2 – Metastatic (M1a) disease with endobronchial tumor blockage: 87% of the respondents would use conventional radiotherapy for symptoms such as hemoptysis, intractable cough, and pain, and the remainder would use SBRT. Almost half of respondents (49%) recommended EBB or YAG lung re-expansion before external beam radiotherapy.
Conclusion: In our study of VHA ROs and their knowledge of management of advanced (M1a/M1b) lung cancer, we found no distinction in clinical decisions based on demographic profiles. Almost all reported knowledge of evidence-based treatment guidelines for palliative radiotherapy of lung cancer and most recommended treatment according to current guidelines.”