AVAHO

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

[email protected]

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

[email protected]

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

[email protected]

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

[email protected]

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

[email protected]

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

[email protected]

Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.

The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.

Those results are similar to the findings of the pivotal phase 2 JULIET trial evaluating tisa-cel in patients with DLBCL who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.

A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.

The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.

Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.

An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.

Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
 

Predicting outcomes

The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.

A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.

The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.

In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.

“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.

Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”

“These are all real-world data with commercially available products, he noted.
 

Product selection

Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.

Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.

The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.

Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.

[email protected]

Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.

The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.

Those results are similar to the findings of the pivotal phase 2 JULIET trial evaluating tisa-cel in patients with DLBCL who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.

A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.

The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.

Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.

An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.

Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
 

Predicting outcomes

The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.

A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.

The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.

In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.

“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.

Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”

“These are all real-world data with commercially available products, he noted.
 

Product selection

Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.

Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.

The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.

Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.

[email protected]

Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.

The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.

Those results are similar to the findings of the pivotal phase 2 JULIET trial evaluating tisa-cel in patients with DLBCL who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.

A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.

The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.

Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.

An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.

Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
 

Predicting outcomes

The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.

A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.

The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.

In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.

“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.

Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”

“These are all real-world data with commercially available products, he noted.
 

Product selection

Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.

Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.

The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.

Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.

[email protected]

Of four surgical procedures for breast cancer that have been determined to be of low value because they yield no meaningful clinical benefit, two continue to be utilized. In fact, the use of two of these procedures has increased in the United States, new research shows.

“This is the first study to [evaluate] all four of the low-value breast cancer procedures at the same time and try to draw some conclusions on practice patterns across facilities,” said senior author Lesly A. Dossett, MD, MPH, Center for Health Outcomes and Policy, the University of Michigan, Ann Arbor.

The two low-value procedures that have increased in use are contralateral prophylactic mastectomy for average-risk women with unilateral cancer and sentinel lymph node biopsy for clinically node-negative women aged 70 years and older with hormone receptor–positive (HR+) cancer.

“This suggests that formal efforts to reduce low value care through dissemination of guidelines, education of patients or providers, or alignment of incentives will be necessary to achieve full deimplementation,” she told this news organization.

The researchers emphasize that the providing of services that have no clinically meaningful benefit is a national epidemic, costing the United States more than $100 billion dollars annually.

These trends are notable and likely reflect a broad range of factors, commented Katharine Yao, MD, chief of the division of surgical oncology at the NorthShore University HealthSystem, Evanston, Ill.

“I think the better message here is not so much that facilities are doing too many low-value procedures but more that these procedures are still being performed, and the trends show increased rates over the years – why is that?”

“Perhaps there are other factors here we need to explore: why do these procedures persist, and why, despite the Choosing Wisely campaign, [do] they continue to increase?” she said in an interview. “Maybe there is something we can learn here about patient and physician preferences that perhaps we should be paying more attention to.”

The study was published on Feb. 3 in JAMA Surgery.

For the analysis, Dr. Dossett and her colleagues evaluated surgical data from the National Cancer Database. They examined data from more than 1,500 surgical facilities and from surgeries involving 920,256 women in the United States who were diagnosed with breast cancer between 2004 and 2016.

The team focused on four procedures that have been determined to be of low value by Choosing Wisely, a campaign of the American Board of Internal Medicine Foundation, on the basis of recommendations of the American College of Surgeons, the Society for Surgical Oncology, and the American Society for Breast Surgeons.

The results show that, for two of the four low-value procedures, use declined significantly over the study period. These two procedures were axillary lymph node dissection for limited nodal disease, for patients undergoing lumpectomy and radiotherapy, and lumpectomy re-excision for patients whose surgical margins were close but were negative for invasive cancer.

Axillary lymph node dissection declined from 63% in 2004 to 14% in 2016. The steepest reduction was seen soon after data from the Z0011 study were published in 2010. The rates for this procedure halved in the following year, from 62% in 2010 to 31% in 2011 (P < .001).

Likewise, reoperation rates after lumpectomy dropped from 19% in 2004 to 15% in 2016. The sharpest decline, from 18% in 2013 to 16% in 2014, corresponded to the publishing of the SSO/ASTRO consensus statement, which designated a negative margin as having “no tumor on ink.”

Two of the four low-value procedures increased in use during the study period.

Rates of contralateral prophylactic mastectomy increased nearly 2.5-fold among women with unilateral breast cancer undergoing mastectomy, from 11% in 2004 to 26% in 2016, despite SSO guidelines issued in 2007 recommending that the procedure not be used for women at average risk.

In addition, rates of sentinel lymph node biopsy among women aged 70 years and older with clinically node-negative HR+ breast cancer increased from 78% in 2004 to 87% in 2012. There was no significant decline in the use of this procedure, even after the CALGB 9343 trial from the Cancer and Leukemia Group B showed no survival benefit in 2013.
 

Patterns at hospitals vary

The authors of the study also examined hospital factors, which can heavily influence choice of procedure.

These results showed that the greatest reductions of the low-value breast cancer procedures occurred at academic research programs and high-volume surgical facilities. Elsewhere, the rates varied widely.

Interfacility rates of axillary lymph node dissection ranged from 7% to 47%; lumpectomy reoperation rates ranged from 3% to 62%; contralateral prophylactic mastectomy rates ranged from 9% to 67%; and sentinel lymph node biopsy rates ranged from 25% to 97%.

Being an outlier for use of one procedure did not necessarily translate to nonconformity for others. Factors such as a hospital’s volume of breast cancer cases or the type of facility did not appear to influence rates of axillary lymph node dissection or lumpectomy reoperation.

However, the rates of contralateral prophylactic mastectomy were significantly higher in high-volume centers and integrated network cancer programs, compared with community cancer programs (23% vs. 2%; P < .001).

Dr. Dossett said the lack of consistency was somewhat unexpected.

“We expected we would find some facilities were constantly good or bad at deimplementation or that there would be stronger associations between certain facility characteristics and performance,” she said. “That really wasn’t the case, and most facilities had mixed performance.”
 

Evidence may or may not influence trends

The authors speculate on why the low-value designation is in some cases being ignored.

The evidence regarding the risk for lymphedema related to axillary lymph node dissection procedure appears to have helped reduce its use, they note.

However, surgeons have been much less convinced of benefits in omitting sentinel lymph node biopsy, either because they are unfamiliar with the recommendations to avoid the procedure, or they may feel the procedure adds only minimal time and risk to a patient’s operation, the authors explain.

Patients may be convinced to opt to omit sentinel lymph node biopsy if they are properly counseled regarding the risks and benefits of the procedure, Dr. Dossett commented.

Dr. Yao added that, for elderly patients, age can play an important role in sentinel node biopsy.

“Patients’ life expectancy has increased over the years, and node status may impact adjuvant therapy decisions for these patients, even chemotherapy decisions,” she said.

Pressure to continue to perform contralateral prophylactic mastectomy is believed to be significantly patient driven, Dr. Dossett noted.

“I ultimately think the best way to reduce contralateral prophylactic mastectomy is to encourage women with small cancers to undergo breast-conserving surgery, i.e., lumpectomy, instead of mastectomy,” she explained.

“Once the decision for mastectomy is made, there is often a great deal of momentum towards a contralateral prophylactic mastectomy.”

“Contralateral prophylactic mastectomy is a personal preference that many surgeons are willing to do for their patients,” Dr. Yao explained.

“Although no survival benefit has been demonstrated for this procedure, patients find many other benefits that have nothing to do with survival.”

The authors and Dr. Yao have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Of four surgical procedures for breast cancer that have been determined to be of low value because they yield no meaningful clinical benefit, two continue to be utilized. In fact, the use of two of these procedures has increased in the United States, new research shows.

“This is the first study to [evaluate] all four of the low-value breast cancer procedures at the same time and try to draw some conclusions on practice patterns across facilities,” said senior author Lesly A. Dossett, MD, MPH, Center for Health Outcomes and Policy, the University of Michigan, Ann Arbor.

The two low-value procedures that have increased in use are contralateral prophylactic mastectomy for average-risk women with unilateral cancer and sentinel lymph node biopsy for clinically node-negative women aged 70 years and older with hormone receptor–positive (HR+) cancer.

“This suggests that formal efforts to reduce low value care through dissemination of guidelines, education of patients or providers, or alignment of incentives will be necessary to achieve full deimplementation,” she told this news organization.

The researchers emphasize that the providing of services that have no clinically meaningful benefit is a national epidemic, costing the United States more than $100 billion dollars annually.

These trends are notable and likely reflect a broad range of factors, commented Katharine Yao, MD, chief of the division of surgical oncology at the NorthShore University HealthSystem, Evanston, Ill.

“I think the better message here is not so much that facilities are doing too many low-value procedures but more that these procedures are still being performed, and the trends show increased rates over the years – why is that?”

“Perhaps there are other factors here we need to explore: why do these procedures persist, and why, despite the Choosing Wisely campaign, [do] they continue to increase?” she said in an interview. “Maybe there is something we can learn here about patient and physician preferences that perhaps we should be paying more attention to.”

The study was published on Feb. 3 in JAMA Surgery.

For the analysis, Dr. Dossett and her colleagues evaluated surgical data from the National Cancer Database. They examined data from more than 1,500 surgical facilities and from surgeries involving 920,256 women in the United States who were diagnosed with breast cancer between 2004 and 2016.

The team focused on four procedures that have been determined to be of low value by Choosing Wisely, a campaign of the American Board of Internal Medicine Foundation, on the basis of recommendations of the American College of Surgeons, the Society for Surgical Oncology, and the American Society for Breast Surgeons.

The results show that, for two of the four low-value procedures, use declined significantly over the study period. These two procedures were axillary lymph node dissection for limited nodal disease, for patients undergoing lumpectomy and radiotherapy, and lumpectomy re-excision for patients whose surgical margins were close but were negative for invasive cancer.

Axillary lymph node dissection declined from 63% in 2004 to 14% in 2016. The steepest reduction was seen soon after data from the Z0011 study were published in 2010. The rates for this procedure halved in the following year, from 62% in 2010 to 31% in 2011 (P < .001).

Likewise, reoperation rates after lumpectomy dropped from 19% in 2004 to 15% in 2016. The sharpest decline, from 18% in 2013 to 16% in 2014, corresponded to the publishing of the SSO/ASTRO consensus statement, which designated a negative margin as having “no tumor on ink.”

Two of the four low-value procedures increased in use during the study period.

Rates of contralateral prophylactic mastectomy increased nearly 2.5-fold among women with unilateral breast cancer undergoing mastectomy, from 11% in 2004 to 26% in 2016, despite SSO guidelines issued in 2007 recommending that the procedure not be used for women at average risk.

In addition, rates of sentinel lymph node biopsy among women aged 70 years and older with clinically node-negative HR+ breast cancer increased from 78% in 2004 to 87% in 2012. There was no significant decline in the use of this procedure, even after the CALGB 9343 trial from the Cancer and Leukemia Group B showed no survival benefit in 2013.
 

Patterns at hospitals vary

The authors of the study also examined hospital factors, which can heavily influence choice of procedure.

These results showed that the greatest reductions of the low-value breast cancer procedures occurred at academic research programs and high-volume surgical facilities. Elsewhere, the rates varied widely.

Interfacility rates of axillary lymph node dissection ranged from 7% to 47%; lumpectomy reoperation rates ranged from 3% to 62%; contralateral prophylactic mastectomy rates ranged from 9% to 67%; and sentinel lymph node biopsy rates ranged from 25% to 97%.

Being an outlier for use of one procedure did not necessarily translate to nonconformity for others. Factors such as a hospital’s volume of breast cancer cases or the type of facility did not appear to influence rates of axillary lymph node dissection or lumpectomy reoperation.

However, the rates of contralateral prophylactic mastectomy were significantly higher in high-volume centers and integrated network cancer programs, compared with community cancer programs (23% vs. 2%; P < .001).

Dr. Dossett said the lack of consistency was somewhat unexpected.

“We expected we would find some facilities were constantly good or bad at deimplementation or that there would be stronger associations between certain facility characteristics and performance,” she said. “That really wasn’t the case, and most facilities had mixed performance.”
 

Evidence may or may not influence trends

The authors speculate on why the low-value designation is in some cases being ignored.

The evidence regarding the risk for lymphedema related to axillary lymph node dissection procedure appears to have helped reduce its use, they note.

However, surgeons have been much less convinced of benefits in omitting sentinel lymph node biopsy, either because they are unfamiliar with the recommendations to avoid the procedure, or they may feel the procedure adds only minimal time and risk to a patient’s operation, the authors explain.

Patients may be convinced to opt to omit sentinel lymph node biopsy if they are properly counseled regarding the risks and benefits of the procedure, Dr. Dossett commented.

Dr. Yao added that, for elderly patients, age can play an important role in sentinel node biopsy.

“Patients’ life expectancy has increased over the years, and node status may impact adjuvant therapy decisions for these patients, even chemotherapy decisions,” she said.

Pressure to continue to perform contralateral prophylactic mastectomy is believed to be significantly patient driven, Dr. Dossett noted.

“I ultimately think the best way to reduce contralateral prophylactic mastectomy is to encourage women with small cancers to undergo breast-conserving surgery, i.e., lumpectomy, instead of mastectomy,” she explained.

“Once the decision for mastectomy is made, there is often a great deal of momentum towards a contralateral prophylactic mastectomy.”

“Contralateral prophylactic mastectomy is a personal preference that many surgeons are willing to do for their patients,” Dr. Yao explained.

“Although no survival benefit has been demonstrated for this procedure, patients find many other benefits that have nothing to do with survival.”

The authors and Dr. Yao have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Of four surgical procedures for breast cancer that have been determined to be of low value because they yield no meaningful clinical benefit, two continue to be utilized. In fact, the use of two of these procedures has increased in the United States, new research shows.

“This is the first study to [evaluate] all four of the low-value breast cancer procedures at the same time and try to draw some conclusions on practice patterns across facilities,” said senior author Lesly A. Dossett, MD, MPH, Center for Health Outcomes and Policy, the University of Michigan, Ann Arbor.

The two low-value procedures that have increased in use are contralateral prophylactic mastectomy for average-risk women with unilateral cancer and sentinel lymph node biopsy for clinically node-negative women aged 70 years and older with hormone receptor–positive (HR+) cancer.

“This suggests that formal efforts to reduce low value care through dissemination of guidelines, education of patients or providers, or alignment of incentives will be necessary to achieve full deimplementation,” she told this news organization.

The researchers emphasize that the providing of services that have no clinically meaningful benefit is a national epidemic, costing the United States more than $100 billion dollars annually.

These trends are notable and likely reflect a broad range of factors, commented Katharine Yao, MD, chief of the division of surgical oncology at the NorthShore University HealthSystem, Evanston, Ill.

“I think the better message here is not so much that facilities are doing too many low-value procedures but more that these procedures are still being performed, and the trends show increased rates over the years – why is that?”

“Perhaps there are other factors here we need to explore: why do these procedures persist, and why, despite the Choosing Wisely campaign, [do] they continue to increase?” she said in an interview. “Maybe there is something we can learn here about patient and physician preferences that perhaps we should be paying more attention to.”

The study was published on Feb. 3 in JAMA Surgery.

For the analysis, Dr. Dossett and her colleagues evaluated surgical data from the National Cancer Database. They examined data from more than 1,500 surgical facilities and from surgeries involving 920,256 women in the United States who were diagnosed with breast cancer between 2004 and 2016.

The team focused on four procedures that have been determined to be of low value by Choosing Wisely, a campaign of the American Board of Internal Medicine Foundation, on the basis of recommendations of the American College of Surgeons, the Society for Surgical Oncology, and the American Society for Breast Surgeons.

The results show that, for two of the four low-value procedures, use declined significantly over the study period. These two procedures were axillary lymph node dissection for limited nodal disease, for patients undergoing lumpectomy and radiotherapy, and lumpectomy re-excision for patients whose surgical margins were close but were negative for invasive cancer.

Axillary lymph node dissection declined from 63% in 2004 to 14% in 2016. The steepest reduction was seen soon after data from the Z0011 study were published in 2010. The rates for this procedure halved in the following year, from 62% in 2010 to 31% in 2011 (P < .001).

Likewise, reoperation rates after lumpectomy dropped from 19% in 2004 to 15% in 2016. The sharpest decline, from 18% in 2013 to 16% in 2014, corresponded to the publishing of the SSO/ASTRO consensus statement, which designated a negative margin as having “no tumor on ink.”

Two of the four low-value procedures increased in use during the study period.

Rates of contralateral prophylactic mastectomy increased nearly 2.5-fold among women with unilateral breast cancer undergoing mastectomy, from 11% in 2004 to 26% in 2016, despite SSO guidelines issued in 2007 recommending that the procedure not be used for women at average risk.

In addition, rates of sentinel lymph node biopsy among women aged 70 years and older with clinically node-negative HR+ breast cancer increased from 78% in 2004 to 87% in 2012. There was no significant decline in the use of this procedure, even after the CALGB 9343 trial from the Cancer and Leukemia Group B showed no survival benefit in 2013.
 

Patterns at hospitals vary

The authors of the study also examined hospital factors, which can heavily influence choice of procedure.

These results showed that the greatest reductions of the low-value breast cancer procedures occurred at academic research programs and high-volume surgical facilities. Elsewhere, the rates varied widely.

Interfacility rates of axillary lymph node dissection ranged from 7% to 47%; lumpectomy reoperation rates ranged from 3% to 62%; contralateral prophylactic mastectomy rates ranged from 9% to 67%; and sentinel lymph node biopsy rates ranged from 25% to 97%.

Being an outlier for use of one procedure did not necessarily translate to nonconformity for others. Factors such as a hospital’s volume of breast cancer cases or the type of facility did not appear to influence rates of axillary lymph node dissection or lumpectomy reoperation.

However, the rates of contralateral prophylactic mastectomy were significantly higher in high-volume centers and integrated network cancer programs, compared with community cancer programs (23% vs. 2%; P < .001).

Dr. Dossett said the lack of consistency was somewhat unexpected.

“We expected we would find some facilities were constantly good or bad at deimplementation or that there would be stronger associations between certain facility characteristics and performance,” she said. “That really wasn’t the case, and most facilities had mixed performance.”
 

Evidence may or may not influence trends

The authors speculate on why the low-value designation is in some cases being ignored.

The evidence regarding the risk for lymphedema related to axillary lymph node dissection procedure appears to have helped reduce its use, they note.

However, surgeons have been much less convinced of benefits in omitting sentinel lymph node biopsy, either because they are unfamiliar with the recommendations to avoid the procedure, or they may feel the procedure adds only minimal time and risk to a patient’s operation, the authors explain.

Patients may be convinced to opt to omit sentinel lymph node biopsy if they are properly counseled regarding the risks and benefits of the procedure, Dr. Dossett commented.

Dr. Yao added that, for elderly patients, age can play an important role in sentinel node biopsy.

“Patients’ life expectancy has increased over the years, and node status may impact adjuvant therapy decisions for these patients, even chemotherapy decisions,” she said.

Pressure to continue to perform contralateral prophylactic mastectomy is believed to be significantly patient driven, Dr. Dossett noted.

“I ultimately think the best way to reduce contralateral prophylactic mastectomy is to encourage women with small cancers to undergo breast-conserving surgery, i.e., lumpectomy, instead of mastectomy,” she explained.

“Once the decision for mastectomy is made, there is often a great deal of momentum towards a contralateral prophylactic mastectomy.”

“Contralateral prophylactic mastectomy is a personal preference that many surgeons are willing to do for their patients,” Dr. Yao explained.

“Although no survival benefit has been demonstrated for this procedure, patients find many other benefits that have nothing to do with survival.”

The authors and Dr. Yao have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

After a long day in hematology clinic, I skimmed the inpatient list to see if any of my patients had been admitted. Seeing Ms. Short’s name (changed for privacy), a delightful African American woman I met during my early days of fellowship, had me making the trek to the hospital. She was living with multiple myeloma complicated by extramedullary manifestations that had significantly impacted her quality of life.

During our first encounter, she showed me a growing left subscapular mass the size of an orange that was erythematous, hot, painful, and irritated. As an enthusiastic first-year fellow, I wanted to be aggressive in addressing her concerns in response to her obvious distress about this mass. Ultimately, she left clinic with antibiotics and an appointment with radiation oncology to see if they could use radiation to shrink the subscapular mass.

When I went back in to discuss the plan with her, she grabbed my hand, looked me in my eyes and said: “Thank you, I’ve been mentioning this for a while and you’re the first person to get something done about it.” In that moment I knew that she felt seen.

By the time I made it over to the hospital, she was getting settled in her room to start another cycle of cytoreductive chemotherapy.

“I told them I had a Black doctor!” she exclaimed as I walked into her hospital room. “I was looking for you today in clinic ... I kept telling them I had a Black doctor, but the nurses kept telling me no, that there were only Black nurse practitioners.” She had repeatedly told the staff that I, her “Black doctor,” did indeed exist, and she went on to describe me as “you know, the [heavy-chested] and short Black doctor I saw early this fall.” To this day, her description still makes me chuckle.

Though I laughed at her description, it hurt that I had worked in a clinic for 6 months yet was invisible. Initially disappointed, I left Ms. Short’s room with a smile on my face, energized and encouraged.

My time with Ms. Short prompted me to ruminate on my experience as a Black physician. To put it in perspective, 5% of all physicians are Black, 2% are Black women, and 2.3% are oncologists, even though African Americans make up 13% of the general U.S. population. I reside in a space where I am simultaneously scrutinized because I am one of the few (or the only) Black physicians in the building, and yet I am invisible because my colleagues and coworkers routinely ignore my presence.

Black physicians, let alone hematologists, are so rare that nurses often cannot fathom that a Black woman could be more than a nurse practitioner. Sadly, this is the tip of the iceberg of some of the negative experiences I, and other Black doctors, have had.

How I present myself must be carefully curated to make progress in my career. My peers and superiors seem to hear me better when my hair is straight and not in its naturally curly state. My introversion has been interpreted as being standoffish or disinterested. Any tone other than happy is interpreted as “aggressive” or “angry”. Talking “too much” to Black support staff was reported to my program, as it was viewed as suspicious, disruptive, and “appearances matter”.

I am also expected to be nurturing in ways that White physicians are not required to be. In my presence, White physicians have denigrated an entire patient population that is disproportionately Black by calling them “sicklers.” If there is an interpersonal conflict, I must think about the long-term consequences of voicing my perspective. My non-Black colleagues do not have to think about these things.

Imagine dealing with this at work, then on your commute home being worried about the reality that you may be pulled over and become the next name on the ever-growing list of Black women and men murdered at the hands of police. The cognitive and emotional impact of being invisible is immense and cumulative over the years.

My Blackness creates a bias of inferiority that cannot be overcome by respectability, compliance, professionalism, training, and expertise. This is glaringly apparent on both sides of the physician-patient relationship. Black patients’ concerns are routinely overlooked and dismissed, as seen with Ms. Short, and are reflected in the Black maternal death rate, pain control in Black versus White patients, and personal experience as a patient and an advocate for my family members.

Patients have looked me in the face and said, “all lives matter,” displaying their refusal to recognize that systematic racism and inequality exist. These facts and experiences are the antithesis of “primum non nocere.”

Sadly, my and Ms. Short’s experiences are not singular ones, and racial bias in medicine is a diagnosed, but untreated cancer. Like the malignancies I treat, ignoring the problem has not made it go away; therefore, it continues to fester and spread, causing more destruction. It is of great importance and concern that all physicians recognize, reflect, and correct their implicit biases not only toward their patients, but also colleagues and trainees.

It seems that health care professionals can talk the talk, as many statements have been made against racism and implicit bias in medicine, but can we take true and meaningful action to begin the journey to equity and justice?

I would like to thank Adrienne Glover, MD, MaKenzie Hodge, MD, Maranatha McLean, MD, and Darion Showell, MD, for our stimulating conversations that helped me put pen to paper. I’d also like to thank my family for being my editors.

Daphanie D. Taylor, MD, is a hematology/oncology fellow PGY-6 at Levine Cancer Institute, Charlotte, N.C.

References and further reading

Roy L. “‘It’s My Calling To Change The Statistics’: Why We Need More Black Female Physicians.” Forbes Magazine, 27 Feb. 2020.

“Diversity in Medicine: Facts and Figures 2019.” Association of American Medical Colleges, 2019.

“Facts & Figures: Diversity in Oncology.” American Society of Clinical Oncology. 2020 Jan 16.

After a long day in hematology clinic, I skimmed the inpatient list to see if any of my patients had been admitted. Seeing Ms. Short’s name (changed for privacy), a delightful African American woman I met during my early days of fellowship, had me making the trek to the hospital. She was living with multiple myeloma complicated by extramedullary manifestations that had significantly impacted her quality of life.

During our first encounter, she showed me a growing left subscapular mass the size of an orange that was erythematous, hot, painful, and irritated. As an enthusiastic first-year fellow, I wanted to be aggressive in addressing her concerns in response to her obvious distress about this mass. Ultimately, she left clinic with antibiotics and an appointment with radiation oncology to see if they could use radiation to shrink the subscapular mass.

When I went back in to discuss the plan with her, she grabbed my hand, looked me in my eyes and said: “Thank you, I’ve been mentioning this for a while and you’re the first person to get something done about it.” In that moment I knew that she felt seen.

By the time I made it over to the hospital, she was getting settled in her room to start another cycle of cytoreductive chemotherapy.

“I told them I had a Black doctor!” she exclaimed as I walked into her hospital room. “I was looking for you today in clinic ... I kept telling them I had a Black doctor, but the nurses kept telling me no, that there were only Black nurse practitioners.” She had repeatedly told the staff that I, her “Black doctor,” did indeed exist, and she went on to describe me as “you know, the [heavy-chested] and short Black doctor I saw early this fall.” To this day, her description still makes me chuckle.

Though I laughed at her description, it hurt that I had worked in a clinic for 6 months yet was invisible. Initially disappointed, I left Ms. Short’s room with a smile on my face, energized and encouraged.

My time with Ms. Short prompted me to ruminate on my experience as a Black physician. To put it in perspective, 5% of all physicians are Black, 2% are Black women, and 2.3% are oncologists, even though African Americans make up 13% of the general U.S. population. I reside in a space where I am simultaneously scrutinized because I am one of the few (or the only) Black physicians in the building, and yet I am invisible because my colleagues and coworkers routinely ignore my presence.

Black physicians, let alone hematologists, are so rare that nurses often cannot fathom that a Black woman could be more than a nurse practitioner. Sadly, this is the tip of the iceberg of some of the negative experiences I, and other Black doctors, have had.

How I present myself must be carefully curated to make progress in my career. My peers and superiors seem to hear me better when my hair is straight and not in its naturally curly state. My introversion has been interpreted as being standoffish or disinterested. Any tone other than happy is interpreted as “aggressive” or “angry”. Talking “too much” to Black support staff was reported to my program, as it was viewed as suspicious, disruptive, and “appearances matter”.

I am also expected to be nurturing in ways that White physicians are not required to be. In my presence, White physicians have denigrated an entire patient population that is disproportionately Black by calling them “sicklers.” If there is an interpersonal conflict, I must think about the long-term consequences of voicing my perspective. My non-Black colleagues do not have to think about these things.

Imagine dealing with this at work, then on your commute home being worried about the reality that you may be pulled over and become the next name on the ever-growing list of Black women and men murdered at the hands of police. The cognitive and emotional impact of being invisible is immense and cumulative over the years.

My Blackness creates a bias of inferiority that cannot be overcome by respectability, compliance, professionalism, training, and expertise. This is glaringly apparent on both sides of the physician-patient relationship. Black patients’ concerns are routinely overlooked and dismissed, as seen with Ms. Short, and are reflected in the Black maternal death rate, pain control in Black versus White patients, and personal experience as a patient and an advocate for my family members.

Patients have looked me in the face and said, “all lives matter,” displaying their refusal to recognize that systematic racism and inequality exist. These facts and experiences are the antithesis of “primum non nocere.”

Sadly, my and Ms. Short’s experiences are not singular ones, and racial bias in medicine is a diagnosed, but untreated cancer. Like the malignancies I treat, ignoring the problem has not made it go away; therefore, it continues to fester and spread, causing more destruction. It is of great importance and concern that all physicians recognize, reflect, and correct their implicit biases not only toward their patients, but also colleagues and trainees.

It seems that health care professionals can talk the talk, as many statements have been made against racism and implicit bias in medicine, but can we take true and meaningful action to begin the journey to equity and justice?

I would like to thank Adrienne Glover, MD, MaKenzie Hodge, MD, Maranatha McLean, MD, and Darion Showell, MD, for our stimulating conversations that helped me put pen to paper. I’d also like to thank my family for being my editors.

Daphanie D. Taylor, MD, is a hematology/oncology fellow PGY-6 at Levine Cancer Institute, Charlotte, N.C.

References and further reading

Roy L. “‘It’s My Calling To Change The Statistics’: Why We Need More Black Female Physicians.” Forbes Magazine, 27 Feb. 2020.

“Diversity in Medicine: Facts and Figures 2019.” Association of American Medical Colleges, 2019.

“Facts & Figures: Diversity in Oncology.” American Society of Clinical Oncology. 2020 Jan 16.

After a long day in hematology clinic, I skimmed the inpatient list to see if any of my patients had been admitted. Seeing Ms. Short’s name (changed for privacy), a delightful African American woman I met during my early days of fellowship, had me making the trek to the hospital. She was living with multiple myeloma complicated by extramedullary manifestations that had significantly impacted her quality of life.

During our first encounter, she showed me a growing left subscapular mass the size of an orange that was erythematous, hot, painful, and irritated. As an enthusiastic first-year fellow, I wanted to be aggressive in addressing her concerns in response to her obvious distress about this mass. Ultimately, she left clinic with antibiotics and an appointment with radiation oncology to see if they could use radiation to shrink the subscapular mass.

When I went back in to discuss the plan with her, she grabbed my hand, looked me in my eyes and said: “Thank you, I’ve been mentioning this for a while and you’re the first person to get something done about it.” In that moment I knew that she felt seen.

By the time I made it over to the hospital, she was getting settled in her room to start another cycle of cytoreductive chemotherapy.

“I told them I had a Black doctor!” she exclaimed as I walked into her hospital room. “I was looking for you today in clinic ... I kept telling them I had a Black doctor, but the nurses kept telling me no, that there were only Black nurse practitioners.” She had repeatedly told the staff that I, her “Black doctor,” did indeed exist, and she went on to describe me as “you know, the [heavy-chested] and short Black doctor I saw early this fall.” To this day, her description still makes me chuckle.

Though I laughed at her description, it hurt that I had worked in a clinic for 6 months yet was invisible. Initially disappointed, I left Ms. Short’s room with a smile on my face, energized and encouraged.

My time with Ms. Short prompted me to ruminate on my experience as a Black physician. To put it in perspective, 5% of all physicians are Black, 2% are Black women, and 2.3% are oncologists, even though African Americans make up 13% of the general U.S. population. I reside in a space where I am simultaneously scrutinized because I am one of the few (or the only) Black physicians in the building, and yet I am invisible because my colleagues and coworkers routinely ignore my presence.

Black physicians, let alone hematologists, are so rare that nurses often cannot fathom that a Black woman could be more than a nurse practitioner. Sadly, this is the tip of the iceberg of some of the negative experiences I, and other Black doctors, have had.

How I present myself must be carefully curated to make progress in my career. My peers and superiors seem to hear me better when my hair is straight and not in its naturally curly state. My introversion has been interpreted as being standoffish or disinterested. Any tone other than happy is interpreted as “aggressive” or “angry”. Talking “too much” to Black support staff was reported to my program, as it was viewed as suspicious, disruptive, and “appearances matter”.

I am also expected to be nurturing in ways that White physicians are not required to be. In my presence, White physicians have denigrated an entire patient population that is disproportionately Black by calling them “sicklers.” If there is an interpersonal conflict, I must think about the long-term consequences of voicing my perspective. My non-Black colleagues do not have to think about these things.

Imagine dealing with this at work, then on your commute home being worried about the reality that you may be pulled over and become the next name on the ever-growing list of Black women and men murdered at the hands of police. The cognitive and emotional impact of being invisible is immense and cumulative over the years.

My Blackness creates a bias of inferiority that cannot be overcome by respectability, compliance, professionalism, training, and expertise. This is glaringly apparent on both sides of the physician-patient relationship. Black patients’ concerns are routinely overlooked and dismissed, as seen with Ms. Short, and are reflected in the Black maternal death rate, pain control in Black versus White patients, and personal experience as a patient and an advocate for my family members.

Patients have looked me in the face and said, “all lives matter,” displaying their refusal to recognize that systematic racism and inequality exist. These facts and experiences are the antithesis of “primum non nocere.”

Sadly, my and Ms. Short’s experiences are not singular ones, and racial bias in medicine is a diagnosed, but untreated cancer. Like the malignancies I treat, ignoring the problem has not made it go away; therefore, it continues to fester and spread, causing more destruction. It is of great importance and concern that all physicians recognize, reflect, and correct their implicit biases not only toward their patients, but also colleagues and trainees.

It seems that health care professionals can talk the talk, as many statements have been made against racism and implicit bias in medicine, but can we take true and meaningful action to begin the journey to equity and justice?

I would like to thank Adrienne Glover, MD, MaKenzie Hodge, MD, Maranatha McLean, MD, and Darion Showell, MD, for our stimulating conversations that helped me put pen to paper. I’d also like to thank my family for being my editors.

Daphanie D. Taylor, MD, is a hematology/oncology fellow PGY-6 at Levine Cancer Institute, Charlotte, N.C.

References and further reading

Roy L. “‘It’s My Calling To Change The Statistics’: Why We Need More Black Female Physicians.” Forbes Magazine, 27 Feb. 2020.

“Diversity in Medicine: Facts and Figures 2019.” Association of American Medical Colleges, 2019.

“Facts & Figures: Diversity in Oncology.” American Society of Clinical Oncology. 2020 Jan 16.

Patients with advanced melanoma and preexisting autoimmune diseases (AIDs) who were treated with immune checkpoint inhibitors (ICIs) responded well and did not suffer more grade 3 or higher immune-related adverse events than patients without an AID, a new study finds, although some concerns were raised regarding patients with inflammatory bowel disease (IBD).

“To our knowledge, this is the first study to bridge this knowledge gap by presenting ‘real-world’ data on the safety and efficacy of ICI on a national scale,” wrote Monique K. van der Kooij, MD, of Leiden (the Netherlands) University Medical Center and coauthors. The study was published online in Annals of Internal Medicine.

To investigate ICI use and response among this specific subset of melanoma patients, the researchers launched a nationwide cohort study set in the Netherlands. Data were gathered via the Dutch Melanoma Treatment Registry (DMTR), in which 4,367 patients with advanced melanoma were enrolled between July 2013 and July 2018.

Within that cohort, 415 (9.5%) had preexisting AIDs. Nearly 55% had rheumatologic AIDs (n = 227) – which included RA, systemic lupus erythematosus, scleroderma, sarcoidosis, and vasculitis – with the next most frequent being endocrine AID (n = 143) and IBD (n = 55). Patients with AID were older than patients without (67 vs. 63 years) and were more likely to be female (53% vs. 41%).

The ICIs used in the study included anti-CTLA4 (ipilimumab), anti–programmed death 1 (PD-1) (nivolumab or pembrolizumab), or a combination of nivolumab and ipilimumab. Of the patients with AID, 55% (n = 228) were treated with ICI, compared with 58% of patients without AID. A total of 87 AID patients were treated with anti-CTLA4, 187 received anti-PD-1, and 34 received the combination. The combination was not readily available in the Netherlands until 2017, the authors stated, acknowledging that it may be wise to revisit its effects in the coming years.

Incidence of immune-related adverse events

The incidence of immune-related adverse events (irAEs) grade 3 and above for patients with and without AID who were given anti-CTLA4 was 30%. The incidence rate of irAEs was also similar for patients with (17%; 95% confidence interval, 12%-23%) and without (13%; 95% CI, 12%-15%) AID on anti-PD-1. Patients with AIDs who took anti-PD-1 therapy discontinued it more often because of toxicity than did the patients without AIDs.

The combination group had irAE incidence rates of 44% (95% CI, 27%-62%) for patients with AID, compared with 48% (95% CI, 43%-53%) for patients without AIDs. Overall, no patients with AIDs on ICIs died of toxicity, compared with three deaths among patients without AID on anti-CTLA4, five deaths among patients on anti-PD-1, and one patient on the combination.

Patients with IBD had a notably higher risk of anti-PD-1–induced colitis (19%; 95% CI, 7%-37%), compared with patients with other AIDs (3%; 95% CI, 0%-6%) and patients without AIDs (2%; 95% CI, 2%-3%). IBD patients were also more likely than all other groups on ICIs to stop treatment because of toxicity, leading the researchers to note that “close monitoring in patients with IBD is advised.”

Overall survival after diagnosis was similar in patients with AIDs (median, 13 months; 95% CI, 10-16 months) and without (median, 14 months; 95% CI, 13-15 months), as was the objective response rate to anti-CTLA4 treatment (10% vs. 16%), anti-PD-1 treatment (40% vs. 44%), and combination therapy (39% vs. 43%).

Study largely bypasses the effects of checkpoint inhibitors on RA patients

“For detail, you can’t look to this study,” Anne R. Bass, MD, of the division of rheumatology at the Hospital for Special Surgery in New York, said in an interview. “But for a big-picture look at ‘how safe are checkpoint inhibitors,’ I think it’s an important one.”

Dr. Bass noted that the investigators lumped certain elements together and bypassed others, including their focus on grade 3 or higher adverse events. That was a decision the authors themselves recognized as a potential limitation of their research.

“Understandably, they were worried about life-threatening adverse events, and that’s fine,” she said. But for patients with arthritis who flare, their events are usually grade 2 or even grade 1 and therefore not captured or analyzed in the study. “This does not really address the risk of flare in an RA patient.”

She also questioned their grouping of AIDs, with a bevy of rheumatic diseases categorized as one cluster and the “other” group being particularly broad in its inclusion of “all AIDs not listed” – though only eight patients were placed into that group.

That said, the researchers relied on an oncology database, not one aimed at AID or adverse events. “The numbers are so much bigger than any other study in this area that’s been done,” she said. “It’s both a strength and a weakness of this kind of database.”

Indeed, the authors considered their use of nationwide, population-based data from the DMTR a benefit, calling it “a strength of our approach.”

The DMTR was funded by a grant from the Netherlands Organization for Health Research and Development and sponsored by Bristol-Myers Squibb, Novartis, Roche Nederland, Merck Sharp & Dohme, and Pierre Fabre via the Dutch Institute for Clinical Auditing.

Patients with advanced melanoma and preexisting autoimmune diseases (AIDs) who were treated with immune checkpoint inhibitors (ICIs) responded well and did not suffer more grade 3 or higher immune-related adverse events than patients without an AID, a new study finds, although some concerns were raised regarding patients with inflammatory bowel disease (IBD).

“To our knowledge, this is the first study to bridge this knowledge gap by presenting ‘real-world’ data on the safety and efficacy of ICI on a national scale,” wrote Monique K. van der Kooij, MD, of Leiden (the Netherlands) University Medical Center and coauthors. The study was published online in Annals of Internal Medicine.

To investigate ICI use and response among this specific subset of melanoma patients, the researchers launched a nationwide cohort study set in the Netherlands. Data were gathered via the Dutch Melanoma Treatment Registry (DMTR), in which 4,367 patients with advanced melanoma were enrolled between July 2013 and July 2018.

Within that cohort, 415 (9.5%) had preexisting AIDs. Nearly 55% had rheumatologic AIDs (n = 227) – which included RA, systemic lupus erythematosus, scleroderma, sarcoidosis, and vasculitis – with the next most frequent being endocrine AID (n = 143) and IBD (n = 55). Patients with AID were older than patients without (67 vs. 63 years) and were more likely to be female (53% vs. 41%).

The ICIs used in the study included anti-CTLA4 (ipilimumab), anti–programmed death 1 (PD-1) (nivolumab or pembrolizumab), or a combination of nivolumab and ipilimumab. Of the patients with AID, 55% (n = 228) were treated with ICI, compared with 58% of patients without AID. A total of 87 AID patients were treated with anti-CTLA4, 187 received anti-PD-1, and 34 received the combination. The combination was not readily available in the Netherlands until 2017, the authors stated, acknowledging that it may be wise to revisit its effects in the coming years.

Incidence of immune-related adverse events

The incidence of immune-related adverse events (irAEs) grade 3 and above for patients with and without AID who were given anti-CTLA4 was 30%. The incidence rate of irAEs was also similar for patients with (17%; 95% confidence interval, 12%-23%) and without (13%; 95% CI, 12%-15%) AID on anti-PD-1. Patients with AIDs who took anti-PD-1 therapy discontinued it more often because of toxicity than did the patients without AIDs.

The combination group had irAE incidence rates of 44% (95% CI, 27%-62%) for patients with AID, compared with 48% (95% CI, 43%-53%) for patients without AIDs. Overall, no patients with AIDs on ICIs died of toxicity, compared with three deaths among patients without AID on anti-CTLA4, five deaths among patients on anti-PD-1, and one patient on the combination.

Patients with IBD had a notably higher risk of anti-PD-1–induced colitis (19%; 95% CI, 7%-37%), compared with patients with other AIDs (3%; 95% CI, 0%-6%) and patients without AIDs (2%; 95% CI, 2%-3%). IBD patients were also more likely than all other groups on ICIs to stop treatment because of toxicity, leading the researchers to note that “close monitoring in patients with IBD is advised.”

Overall survival after diagnosis was similar in patients with AIDs (median, 13 months; 95% CI, 10-16 months) and without (median, 14 months; 95% CI, 13-15 months), as was the objective response rate to anti-CTLA4 treatment (10% vs. 16%), anti-PD-1 treatment (40% vs. 44%), and combination therapy (39% vs. 43%).

Study largely bypasses the effects of checkpoint inhibitors on RA patients

“For detail, you can’t look to this study,” Anne R. Bass, MD, of the division of rheumatology at the Hospital for Special Surgery in New York, said in an interview. “But for a big-picture look at ‘how safe are checkpoint inhibitors,’ I think it’s an important one.”

Dr. Bass noted that the investigators lumped certain elements together and bypassed others, including their focus on grade 3 or higher adverse events. That was a decision the authors themselves recognized as a potential limitation of their research.

“Understandably, they were worried about life-threatening adverse events, and that’s fine,” she said. But for patients with arthritis who flare, their events are usually grade 2 or even grade 1 and therefore not captured or analyzed in the study. “This does not really address the risk of flare in an RA patient.”

She also questioned their grouping of AIDs, with a bevy of rheumatic diseases categorized as one cluster and the “other” group being particularly broad in its inclusion of “all AIDs not listed” – though only eight patients were placed into that group.

That said, the researchers relied on an oncology database, not one aimed at AID or adverse events. “The numbers are so much bigger than any other study in this area that’s been done,” she said. “It’s both a strength and a weakness of this kind of database.”

Indeed, the authors considered their use of nationwide, population-based data from the DMTR a benefit, calling it “a strength of our approach.”

The DMTR was funded by a grant from the Netherlands Organization for Health Research and Development and sponsored by Bristol-Myers Squibb, Novartis, Roche Nederland, Merck Sharp & Dohme, and Pierre Fabre via the Dutch Institute for Clinical Auditing.

Patients with advanced melanoma and preexisting autoimmune diseases (AIDs) who were treated with immune checkpoint inhibitors (ICIs) responded well and did not suffer more grade 3 or higher immune-related adverse events than patients without an AID, a new study finds, although some concerns were raised regarding patients with inflammatory bowel disease (IBD).

“To our knowledge, this is the first study to bridge this knowledge gap by presenting ‘real-world’ data on the safety and efficacy of ICI on a national scale,” wrote Monique K. van der Kooij, MD, of Leiden (the Netherlands) University Medical Center and coauthors. The study was published online in Annals of Internal Medicine.

To investigate ICI use and response among this specific subset of melanoma patients, the researchers launched a nationwide cohort study set in the Netherlands. Data were gathered via the Dutch Melanoma Treatment Registry (DMTR), in which 4,367 patients with advanced melanoma were enrolled between July 2013 and July 2018.

Within that cohort, 415 (9.5%) had preexisting AIDs. Nearly 55% had rheumatologic AIDs (n = 227) – which included RA, systemic lupus erythematosus, scleroderma, sarcoidosis, and vasculitis – with the next most frequent being endocrine AID (n = 143) and IBD (n = 55). Patients with AID were older than patients without (67 vs. 63 years) and were more likely to be female (53% vs. 41%).

The ICIs used in the study included anti-CTLA4 (ipilimumab), anti–programmed death 1 (PD-1) (nivolumab or pembrolizumab), or a combination of nivolumab and ipilimumab. Of the patients with AID, 55% (n = 228) were treated with ICI, compared with 58% of patients without AID. A total of 87 AID patients were treated with anti-CTLA4, 187 received anti-PD-1, and 34 received the combination. The combination was not readily available in the Netherlands until 2017, the authors stated, acknowledging that it may be wise to revisit its effects in the coming years.

Incidence of immune-related adverse events

The incidence of immune-related adverse events (irAEs) grade 3 and above for patients with and without AID who were given anti-CTLA4 was 30%. The incidence rate of irAEs was also similar for patients with (17%; 95% confidence interval, 12%-23%) and without (13%; 95% CI, 12%-15%) AID on anti-PD-1. Patients with AIDs who took anti-PD-1 therapy discontinued it more often because of toxicity than did the patients without AIDs.

The combination group had irAE incidence rates of 44% (95% CI, 27%-62%) for patients with AID, compared with 48% (95% CI, 43%-53%) for patients without AIDs. Overall, no patients with AIDs on ICIs died of toxicity, compared with three deaths among patients without AID on anti-CTLA4, five deaths among patients on anti-PD-1, and one patient on the combination.

Patients with IBD had a notably higher risk of anti-PD-1–induced colitis (19%; 95% CI, 7%-37%), compared with patients with other AIDs (3%; 95% CI, 0%-6%) and patients without AIDs (2%; 95% CI, 2%-3%). IBD patients were also more likely than all other groups on ICIs to stop treatment because of toxicity, leading the researchers to note that “close monitoring in patients with IBD is advised.”

Overall survival after diagnosis was similar in patients with AIDs (median, 13 months; 95% CI, 10-16 months) and without (median, 14 months; 95% CI, 13-15 months), as was the objective response rate to anti-CTLA4 treatment (10% vs. 16%), anti-PD-1 treatment (40% vs. 44%), and combination therapy (39% vs. 43%).

Study largely bypasses the effects of checkpoint inhibitors on RA patients

“For detail, you can’t look to this study,” Anne R. Bass, MD, of the division of rheumatology at the Hospital for Special Surgery in New York, said in an interview. “But for a big-picture look at ‘how safe are checkpoint inhibitors,’ I think it’s an important one.”

Dr. Bass noted that the investigators lumped certain elements together and bypassed others, including their focus on grade 3 or higher adverse events. That was a decision the authors themselves recognized as a potential limitation of their research.

“Understandably, they were worried about life-threatening adverse events, and that’s fine,” she said. But for patients with arthritis who flare, their events are usually grade 2 or even grade 1 and therefore not captured or analyzed in the study. “This does not really address the risk of flare in an RA patient.”

She also questioned their grouping of AIDs, with a bevy of rheumatic diseases categorized as one cluster and the “other” group being particularly broad in its inclusion of “all AIDs not listed” – though only eight patients were placed into that group.

That said, the researchers relied on an oncology database, not one aimed at AID or adverse events. “The numbers are so much bigger than any other study in this area that’s been done,” she said. “It’s both a strength and a weakness of this kind of database.”

Indeed, the authors considered their use of nationwide, population-based data from the DMTR a benefit, calling it “a strength of our approach.”

The DMTR was funded by a grant from the Netherlands Organization for Health Research and Development and sponsored by Bristol-Myers Squibb, Novartis, Roche Nederland, Merck Sharp & Dohme, and Pierre Fabre via the Dutch Institute for Clinical Auditing.

A novel drug that offers multilineage protection from chemotherapy-induced myelosuppression has been approved by the Food and Drug Administration.

The drug, trilaciclib (Cosela, G1 Therapeutics) is administered intravenously as a 30-minute infusion within 4 hours prior to the start of chemotherapy. It is indicated specifically for use in adults with extensive-stage small-cell lung cancer (ES-SCLC) who are receiving chemotherapy.

Trilaciclib is a CDK4/6 inhibitor, and this action appears to protect normal bone marrow cells from the harmful effects of chemotherapy.

“For patients with extensive-stage small-cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” Albert Deisseroth, MD, PhD, of the FDA’s Center for Drug Evaluation and Research, said in an FDA press release.
 

First drug of its type

Trilaciclib “is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to treatment with chemotherapy,” according to the drug’s manufacturer.

Myelosuppression is one of the most severe adverse effects of chemotherapy, and it can be life-threatening. It can increase the risk of infection and lead to severe anemia and/or bleeding.

“These complications impact patients’ quality of life and may also result in chemotherapy dose reductions and delays,” Jeffrey Crawford, MD, of Duke Cancer Institute, Durham, N.C., said in a company press release.

“To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed. By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy.”
 

Approval based on randomized, placebo-controlled trials

The approval of trilaciclib is based on data from three randomized, double-blind, placebo-controlled studies, involving a total of 245 patients with ES-SCLC.

These patients were being treated with chemotherapy regimens that were based on the combination of carboplatin and etoposide (with or without the immunotherapy atezolizumab) or regimens that were based on topotecan.

Before receiving the chemotherapy, patients were randomly assigned to receive trilaciclib or placebo.

Results showed that patients who had received an infusion of trilaciclib before receiving chemotherapy had a lower chance of developing severe neutropenia compared with patients who received a placebo, the FDA noted. In addition, among the patients who did develop severe neutropenia, this had a shorter duration among patients who received trilaciclib than among those who received placebo.

The most common side effects of trilaciclib were fatigue; low levels of calcium, potassium, and phosphate in the blood; increased levels of aspartate aminotransferase; headache; and pneumonia.

The FDA noted that patients should also be advised about injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

The approval received a priority review, based on the drug’s breakthrough therapy designation. As is common for such products, the company plans postmarketing activities that will assess the effects of trilaciclib on disease progression or survival with at least a 2-year follow up. This clinical trial is scheduled to start in 2022.

A version of this article first appeared on Medscape.com.

A novel drug that offers multilineage protection from chemotherapy-induced myelosuppression has been approved by the Food and Drug Administration.

The drug, trilaciclib (Cosela, G1 Therapeutics) is administered intravenously as a 30-minute infusion within 4 hours prior to the start of chemotherapy. It is indicated specifically for use in adults with extensive-stage small-cell lung cancer (ES-SCLC) who are receiving chemotherapy.

Trilaciclib is a CDK4/6 inhibitor, and this action appears to protect normal bone marrow cells from the harmful effects of chemotherapy.

“For patients with extensive-stage small-cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” Albert Deisseroth, MD, PhD, of the FDA’s Center for Drug Evaluation and Research, said in an FDA press release.
 

First drug of its type

Trilaciclib “is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to treatment with chemotherapy,” according to the drug’s manufacturer.

Myelosuppression is one of the most severe adverse effects of chemotherapy, and it can be life-threatening. It can increase the risk of infection and lead to severe anemia and/or bleeding.

“These complications impact patients’ quality of life and may also result in chemotherapy dose reductions and delays,” Jeffrey Crawford, MD, of Duke Cancer Institute, Durham, N.C., said in a company press release.

“To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed. By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy.”
 

Approval based on randomized, placebo-controlled trials

The approval of trilaciclib is based on data from three randomized, double-blind, placebo-controlled studies, involving a total of 245 patients with ES-SCLC.

These patients were being treated with chemotherapy regimens that were based on the combination of carboplatin and etoposide (with or without the immunotherapy atezolizumab) or regimens that were based on topotecan.

Before receiving the chemotherapy, patients were randomly assigned to receive trilaciclib or placebo.

Results showed that patients who had received an infusion of trilaciclib before receiving chemotherapy had a lower chance of developing severe neutropenia compared with patients who received a placebo, the FDA noted. In addition, among the patients who did develop severe neutropenia, this had a shorter duration among patients who received trilaciclib than among those who received placebo.

The most common side effects of trilaciclib were fatigue; low levels of calcium, potassium, and phosphate in the blood; increased levels of aspartate aminotransferase; headache; and pneumonia.

The FDA noted that patients should also be advised about injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

The approval received a priority review, based on the drug’s breakthrough therapy designation. As is common for such products, the company plans postmarketing activities that will assess the effects of trilaciclib on disease progression or survival with at least a 2-year follow up. This clinical trial is scheduled to start in 2022.

A version of this article first appeared on Medscape.com.

A novel drug that offers multilineage protection from chemotherapy-induced myelosuppression has been approved by the Food and Drug Administration.

The drug, trilaciclib (Cosela, G1 Therapeutics) is administered intravenously as a 30-minute infusion within 4 hours prior to the start of chemotherapy. It is indicated specifically for use in adults with extensive-stage small-cell lung cancer (ES-SCLC) who are receiving chemotherapy.

Trilaciclib is a CDK4/6 inhibitor, and this action appears to protect normal bone marrow cells from the harmful effects of chemotherapy.

“For patients with extensive-stage small-cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” Albert Deisseroth, MD, PhD, of the FDA’s Center for Drug Evaluation and Research, said in an FDA press release.
 

First drug of its type

Trilaciclib “is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to treatment with chemotherapy,” according to the drug’s manufacturer.

Myelosuppression is one of the most severe adverse effects of chemotherapy, and it can be life-threatening. It can increase the risk of infection and lead to severe anemia and/or bleeding.

“These complications impact patients’ quality of life and may also result in chemotherapy dose reductions and delays,” Jeffrey Crawford, MD, of Duke Cancer Institute, Durham, N.C., said in a company press release.

“To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed. By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy.”
 

Approval based on randomized, placebo-controlled trials

The approval of trilaciclib is based on data from three randomized, double-blind, placebo-controlled studies, involving a total of 245 patients with ES-SCLC.

These patients were being treated with chemotherapy regimens that were based on the combination of carboplatin and etoposide (with or without the immunotherapy atezolizumab) or regimens that were based on topotecan.

Before receiving the chemotherapy, patients were randomly assigned to receive trilaciclib or placebo.

Results showed that patients who had received an infusion of trilaciclib before receiving chemotherapy had a lower chance of developing severe neutropenia compared with patients who received a placebo, the FDA noted. In addition, among the patients who did develop severe neutropenia, this had a shorter duration among patients who received trilaciclib than among those who received placebo.

The most common side effects of trilaciclib were fatigue; low levels of calcium, potassium, and phosphate in the blood; increased levels of aspartate aminotransferase; headache; and pneumonia.

The FDA noted that patients should also be advised about injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

The approval received a priority review, based on the drug’s breakthrough therapy designation. As is common for such products, the company plans postmarketing activities that will assess the effects of trilaciclib on disease progression or survival with at least a 2-year follow up. This clinical trial is scheduled to start in 2022.

A version of this article first appeared on Medscape.com.

The combined clinical cell-cycle risk (CCR) score – derived from both clinical and genetic factors – can identify patients with intermediate- and high-risk localized prostate cancer who could potentially forgo androgen deprivation therapy (ADT), a retrospective study suggests.

The score can identify patients in whom the risk of metastasis after dose-escalated radiation is so small that adding ADT no longer makes clinical sense, according to investigator Jonathan Tward, MD, PhD, of the Genitourinary Cancer Center at the University of Utah, Salt Lake City.

His group’s study, which included 741 patients, showed that, below a CCR score of 2.112, the 10-year risk of metastasis was 4.2% with radiation therapy (RT) alone and 3.9% with the addition of ADT.

“Whether you have RT alone, RT plus any duration of ADT, insufficient duration ADT, or sufficient ADT duration by guideline standard, the risk of metastasis never exceeds 5% at 10 years” even in high- and very-high-risk men, Dr. Tward said.

He and his team found that half the men in their study with unfavorable intermediate-risk disease, 20% with high-risk disease, and 5% with very-high-risk disease scored below the CCR threshold.

This implies that, for many men, ADT after radiation “adds unnecessary morbidity for an extremely small absolute risk reduction in metastasis-free survival,” Dr. Tward said at the 2021 Genitourinary Cancers Symposium, where he presented the findings (Abstract 195).
 

Value of CCR

The CCR score tells you if the relative metastasis risk reduction with ADT after radiation – about 50% based on clinical trials – translates to an absolute risk reduction that would matter, Dr. Tward said in an interview.

“Each patient has in their own mind what that risk reduction is that works for them,” he added.

For some patients, a 1%-2% drop in absolute risk is worth it, he said, but most patients wouldn’t be willing to endure the side effects of hormone therapy if the absolute benefit is less than 5%.

The CCR score is a validated prognosticator of metastasis and death in localized prostate cancer. It’s an amalgam of traditional clinical risk factors from the Cancer of the Prostate Risk Assessment (CAPRA) score and the cell-cycle progression (CCP) score, which measures expression of cell-cycle proliferation genes for a sense of how quickly tumor cells are dividing.

The CCP test is available commercially as Prolaris. It is used mostly to make the call between active surveillance and treatment, Dr. Tward explained, “but I had a hunch this off-the-shelf test would be very good at” helping with ADT decisions after radiation.
 

‘Uncomfortable’ findings, barriers to acceptance

“People are going to be very uncomfortable with these findings because it’s been ingrained in our heads for the past 20-30 years that you must use hormone therapy with high-risk prostate cancer, and you should use hormone therapy with intermediate risk,” Dr. Tward said.

“It took me a while to believe my own data, but we have used this test for several years to help men decide if they would like to have hormone therapy after radiation. Patients clearly benefit from this information,” he said.

The 2.112 cut point for CCR was determined from a prior study that was presented at GUCS 2020 (Abstract 346) and recently accepted for publication.

In the validation study Dr. Tward presented at GUCS 2021, 70% of patients had intermediate-risk disease, and 30% had high- or very-high-risk disease according to National Comprehensive Cancer Network criteria.

All 741 patients received RT equivalent to at least 75.6 Gy at 1.8 Gy per fraction, with 84% getting or exceeding 79.2 Gy. About half the men (53%) had ADT after RT.

Genetic testing was done on stored biopsy samples years after the men were treated. Half of them were below the CCR threshold of 2.112. For those above it, the 10-year risk of metastasis was 25.3%.

CCR outperformed CCP alone, CAPRA alone, and NCCN risk groupings for predicting metastasis risk after RT.

Though this validation study was “successful,” additional research is needed, according to study discussant Richard Valicenti, MD, of the University of California, Davis.

“Widespread acceptance for routine use faces challenges since no biomarker has been prospectively tested or shown to improve long-term outcome,” Dr. Valicenti said. “Clearly, the CCR score may provide highly precise, personalized estimates and justifies testing in tiered and appropriately powered noninferiority studies according to NCCN risk groups. We eagerly await the completion and reporting of such trials so that we have a more personalized approach to treating men with prostate cancer.”

The current study was funded by Myriad Genetics, the company that developed the Prolaris test. Dr. Tward disclosed relationships with Myriad Genetics, Bayer, Blue Earth Diagnostics, Janssen Scientific Affairs, and Merck. Dr. Valicenti has no disclosures.

[email protected]

The combined clinical cell-cycle risk (CCR) score – derived from both clinical and genetic factors – can identify patients with intermediate- and high-risk localized prostate cancer who could potentially forgo androgen deprivation therapy (ADT), a retrospective study suggests.

The score can identify patients in whom the risk of metastasis after dose-escalated radiation is so small that adding ADT no longer makes clinical sense, according to investigator Jonathan Tward, MD, PhD, of the Genitourinary Cancer Center at the University of Utah, Salt Lake City.

His group’s study, which included 741 patients, showed that, below a CCR score of 2.112, the 10-year risk of metastasis was 4.2% with radiation therapy (RT) alone and 3.9% with the addition of ADT.

“Whether you have RT alone, RT plus any duration of ADT, insufficient duration ADT, or sufficient ADT duration by guideline standard, the risk of metastasis never exceeds 5% at 10 years” even in high- and very-high-risk men, Dr. Tward said.

He and his team found that half the men in their study with unfavorable intermediate-risk disease, 20% with high-risk disease, and 5% with very-high-risk disease scored below the CCR threshold.

This implies that, for many men, ADT after radiation “adds unnecessary morbidity for an extremely small absolute risk reduction in metastasis-free survival,” Dr. Tward said at the 2021 Genitourinary Cancers Symposium, where he presented the findings (Abstract 195).
 

Value of CCR

The CCR score tells you if the relative metastasis risk reduction with ADT after radiation – about 50% based on clinical trials – translates to an absolute risk reduction that would matter, Dr. Tward said in an interview.

“Each patient has in their own mind what that risk reduction is that works for them,” he added.

For some patients, a 1%-2% drop in absolute risk is worth it, he said, but most patients wouldn’t be willing to endure the side effects of hormone therapy if the absolute benefit is less than 5%.

The CCR score is a validated prognosticator of metastasis and death in localized prostate cancer. It’s an amalgam of traditional clinical risk factors from the Cancer of the Prostate Risk Assessment (CAPRA) score and the cell-cycle progression (CCP) score, which measures expression of cell-cycle proliferation genes for a sense of how quickly tumor cells are dividing.

The CCP test is available commercially as Prolaris. It is used mostly to make the call between active surveillance and treatment, Dr. Tward explained, “but I had a hunch this off-the-shelf test would be very good at” helping with ADT decisions after radiation.
 

‘Uncomfortable’ findings, barriers to acceptance

“People are going to be very uncomfortable with these findings because it’s been ingrained in our heads for the past 20-30 years that you must use hormone therapy with high-risk prostate cancer, and you should use hormone therapy with intermediate risk,” Dr. Tward said.

“It took me a while to believe my own data, but we have used this test for several years to help men decide if they would like to have hormone therapy after radiation. Patients clearly benefit from this information,” he said.

The 2.112 cut point for CCR was determined from a prior study that was presented at GUCS 2020 (Abstract 346) and recently accepted for publication.

In the validation study Dr. Tward presented at GUCS 2021, 70% of patients had intermediate-risk disease, and 30% had high- or very-high-risk disease according to National Comprehensive Cancer Network criteria.

All 741 patients received RT equivalent to at least 75.6 Gy at 1.8 Gy per fraction, with 84% getting or exceeding 79.2 Gy. About half the men (53%) had ADT after RT.

Genetic testing was done on stored biopsy samples years after the men were treated. Half of them were below the CCR threshold of 2.112. For those above it, the 10-year risk of metastasis was 25.3%.

CCR outperformed CCP alone, CAPRA alone, and NCCN risk groupings for predicting metastasis risk after RT.

Though this validation study was “successful,” additional research is needed, according to study discussant Richard Valicenti, MD, of the University of California, Davis.

“Widespread acceptance for routine use faces challenges since no biomarker has been prospectively tested or shown to improve long-term outcome,” Dr. Valicenti said. “Clearly, the CCR score may provide highly precise, personalized estimates and justifies testing in tiered and appropriately powered noninferiority studies according to NCCN risk groups. We eagerly await the completion and reporting of such trials so that we have a more personalized approach to treating men with prostate cancer.”

The current study was funded by Myriad Genetics, the company that developed the Prolaris test. Dr. Tward disclosed relationships with Myriad Genetics, Bayer, Blue Earth Diagnostics, Janssen Scientific Affairs, and Merck. Dr. Valicenti has no disclosures.

[email protected]

The combined clinical cell-cycle risk (CCR) score – derived from both clinical and genetic factors – can identify patients with intermediate- and high-risk localized prostate cancer who could potentially forgo androgen deprivation therapy (ADT), a retrospective study suggests.

The score can identify patients in whom the risk of metastasis after dose-escalated radiation is so small that adding ADT no longer makes clinical sense, according to investigator Jonathan Tward, MD, PhD, of the Genitourinary Cancer Center at the University of Utah, Salt Lake City.

His group’s study, which included 741 patients, showed that, below a CCR score of 2.112, the 10-year risk of metastasis was 4.2% with radiation therapy (RT) alone and 3.9% with the addition of ADT.

“Whether you have RT alone, RT plus any duration of ADT, insufficient duration ADT, or sufficient ADT duration by guideline standard, the risk of metastasis never exceeds 5% at 10 years” even in high- and very-high-risk men, Dr. Tward said.

He and his team found that half the men in their study with unfavorable intermediate-risk disease, 20% with high-risk disease, and 5% with very-high-risk disease scored below the CCR threshold.

This implies that, for many men, ADT after radiation “adds unnecessary morbidity for an extremely small absolute risk reduction in metastasis-free survival,” Dr. Tward said at the 2021 Genitourinary Cancers Symposium, where he presented the findings (Abstract 195).
 

Value of CCR

The CCR score tells you if the relative metastasis risk reduction with ADT after radiation – about 50% based on clinical trials – translates to an absolute risk reduction that would matter, Dr. Tward said in an interview.

“Each patient has in their own mind what that risk reduction is that works for them,” he added.

For some patients, a 1%-2% drop in absolute risk is worth it, he said, but most patients wouldn’t be willing to endure the side effects of hormone therapy if the absolute benefit is less than 5%.

The CCR score is a validated prognosticator of metastasis and death in localized prostate cancer. It’s an amalgam of traditional clinical risk factors from the Cancer of the Prostate Risk Assessment (CAPRA) score and the cell-cycle progression (CCP) score, which measures expression of cell-cycle proliferation genes for a sense of how quickly tumor cells are dividing.

The CCP test is available commercially as Prolaris. It is used mostly to make the call between active surveillance and treatment, Dr. Tward explained, “but I had a hunch this off-the-shelf test would be very good at” helping with ADT decisions after radiation.
 

‘Uncomfortable’ findings, barriers to acceptance

“People are going to be very uncomfortable with these findings because it’s been ingrained in our heads for the past 20-30 years that you must use hormone therapy with high-risk prostate cancer, and you should use hormone therapy with intermediate risk,” Dr. Tward said.

“It took me a while to believe my own data, but we have used this test for several years to help men decide if they would like to have hormone therapy after radiation. Patients clearly benefit from this information,” he said.

The 2.112 cut point for CCR was determined from a prior study that was presented at GUCS 2020 (Abstract 346) and recently accepted for publication.

In the validation study Dr. Tward presented at GUCS 2021, 70% of patients had intermediate-risk disease, and 30% had high- or very-high-risk disease according to National Comprehensive Cancer Network criteria.

All 741 patients received RT equivalent to at least 75.6 Gy at 1.8 Gy per fraction, with 84% getting or exceeding 79.2 Gy. About half the men (53%) had ADT after RT.

Genetic testing was done on stored biopsy samples years after the men were treated. Half of them were below the CCR threshold of 2.112. For those above it, the 10-year risk of metastasis was 25.3%.

CCR outperformed CCP alone, CAPRA alone, and NCCN risk groupings for predicting metastasis risk after RT.

Though this validation study was “successful,” additional research is needed, according to study discussant Richard Valicenti, MD, of the University of California, Davis.

“Widespread acceptance for routine use faces challenges since no biomarker has been prospectively tested or shown to improve long-term outcome,” Dr. Valicenti said. “Clearly, the CCR score may provide highly precise, personalized estimates and justifies testing in tiered and appropriately powered noninferiority studies according to NCCN risk groups. We eagerly await the completion and reporting of such trials so that we have a more personalized approach to treating men with prostate cancer.”

The current study was funded by Myriad Genetics, the company that developed the Prolaris test. Dr. Tward disclosed relationships with Myriad Genetics, Bayer, Blue Earth Diagnostics, Janssen Scientific Affairs, and Merck. Dr. Valicenti has no disclosures.

[email protected]