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Immunotherapy shows promise in metastatic cervical cancer
CHICAGO – A small study with just nine patients is sparking enormous hope after demonstrating for the first time that immunotherapy using adoptive T-cell therapy can induce complete remission in metastatic cervical cancer.
A single infusion of human papillomavirus (HPV)-targeted T-cell therapy induced complete responses in two women. A third woman had a partial response, with tumor shrinkage of 39% lasting 3 months.
Follow-up performed during the last week of the two women with complete responses showed no sign of disease 15 and 22 months after treatment.
"This study provides proof of principle that an immunotherapy can induce regression of cervical cancer, and that adoptive T-cell therapy can mediate regression of an epithelial cancer," said lead study author Dr. Christian S. Hinrichs, an investigator with the National Cancer Institute.
Cervical cancer harbors attractive targets for immunotherapy in the HPV E6 and E7 oncoproteins, but clinical trials of immunotherapy in this disease have thus far been disappointing.
The goal with vaccines against HPV is to reduce the future incidence of cervical cancer. But new therapies for advanced-stage disease are desperately needed because chemotherapy is not curative and rarely provides durable palliation, he said during a press briefing at the annual meeting of the American Society of Clinical Oncology.
He noted that one of the patients with a complete response had been previously treated with three different combination cytotoxic chemotherapy regimens for her HPV-16–positive squamous cell carcinoma, while the other had aggressive HPV-18–positive adenocarcinoma that had spread to the pelvis and distant sites despite chemoradiation. Both women were only 36 years old.
The best treatment we have commits women to chemotherapy and/or a biologic for the rest of their lives, which is no more than 2 years for most of the young women being treated, commented Dr. Don S. Dizon, director of the Oncology Sexual Health Clinic at the Massachusetts General Hospital Cancer Center, Boston.
"If all the academic centers can standardize this approach and identify the patients most likely to benefit, we could really reduce the deaths from this disease," he said.
Method
Research using adoptive T-cell therapy (ACT) in epithelial cancers, however, has been limited. ACT has been shown to induce dramatic, complete durable regression of melanoma and certain B-cell malignancies through use of T cells genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARS).
"The difference here is that these are not genetically engineered cells," Dr. Hinrichs said in an interview. "These are naturally occurring T cells that are present in the tumors, grown out, and selected out for their reactivity against tumor antigens [HPV-E6 and -E7]."
The HPV-targeted tumor-infiltrating lymphocytes (TILs) are grown in the laboratory until they number in the billions and then are infused back into the patient. The women are pretreated with a lymphocyte-depleting conditioning regimen of cyclophosphamide and fludarabine (Fludara), and given aldesleukin (Proleukin), dosed to tolerance, after cell infusion.
All patients had HPV-positive cervical cancer and received a median of 81 x 10-9 T cells (range 33-159 x 10-9), Dr. Hinrichs reported.
The two women with complete responses by RECIST criteria demonstrated prolonged repopulation with the HPV-reactive T cells, detectable after 13 months in one and 6 months in the other. Two patients showed no repopulation of T cells and did not respond to treatment.
The most common severe adverse events seen with the therapy were the hematologic toxicities of the conditioning regimen, which occurred in all nine patients, Dr. Hinrichs said in an interview. Five patients had febrile neutropenia and six had infections, primarily positive blood cultures that were treated with antibiotics. All toxicities were completely reversible, and since it’s a one-time therapy, they were better tolerated than if they were repeated in cycles like traditional chemotherapy infusions, he observed.
Though encouraging, Dr. Hinrichs and others urged caution in interpreting these early data. Dr. Steven O’Day, with the University of Southern California, Los Angeles, said it’s costly and labor intensive to gather and manipulate cells and that questions remain about how to make the process more efficient, the therapy less toxic, and to determine whether cells could possibly be manipulated in vivo.
"There’re many questions, but the science is exciting, and it’s giving us an opportunity to direct the immune system against a cancer that traditionally isn’t seen by the immune system very well at all," he said. "So there are lots more to come."
Dr. Hinrichs said they plan to expand the study to 35 women to better define the response rate and that HPV-TIL is also being tested in a separate cohort of patients with noncervical HPV-positive cancers like oropharyngeal, anal, vulvar, and vaginal cancer. Physicians interested in enrolling patients should contact the National Institutes of Health. Patient referrals should be directed to June Kryk ([email protected], 301-451-1929) or Linda Williams ([email protected], 301-402-4124).
The study was supported by the National Cancer Institute, National Institutes of Health. The authors and Dr. Dizon reported no financial disclosures.
CHICAGO – A small study with just nine patients is sparking enormous hope after demonstrating for the first time that immunotherapy using adoptive T-cell therapy can induce complete remission in metastatic cervical cancer.
A single infusion of human papillomavirus (HPV)-targeted T-cell therapy induced complete responses in two women. A third woman had a partial response, with tumor shrinkage of 39% lasting 3 months.
Follow-up performed during the last week of the two women with complete responses showed no sign of disease 15 and 22 months after treatment.
"This study provides proof of principle that an immunotherapy can induce regression of cervical cancer, and that adoptive T-cell therapy can mediate regression of an epithelial cancer," said lead study author Dr. Christian S. Hinrichs, an investigator with the National Cancer Institute.
Cervical cancer harbors attractive targets for immunotherapy in the HPV E6 and E7 oncoproteins, but clinical trials of immunotherapy in this disease have thus far been disappointing.
The goal with vaccines against HPV is to reduce the future incidence of cervical cancer. But new therapies for advanced-stage disease are desperately needed because chemotherapy is not curative and rarely provides durable palliation, he said during a press briefing at the annual meeting of the American Society of Clinical Oncology.
He noted that one of the patients with a complete response had been previously treated with three different combination cytotoxic chemotherapy regimens for her HPV-16–positive squamous cell carcinoma, while the other had aggressive HPV-18–positive adenocarcinoma that had spread to the pelvis and distant sites despite chemoradiation. Both women were only 36 years old.
The best treatment we have commits women to chemotherapy and/or a biologic for the rest of their lives, which is no more than 2 years for most of the young women being treated, commented Dr. Don S. Dizon, director of the Oncology Sexual Health Clinic at the Massachusetts General Hospital Cancer Center, Boston.
"If all the academic centers can standardize this approach and identify the patients most likely to benefit, we could really reduce the deaths from this disease," he said.
Method
Research using adoptive T-cell therapy (ACT) in epithelial cancers, however, has been limited. ACT has been shown to induce dramatic, complete durable regression of melanoma and certain B-cell malignancies through use of T cells genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARS).
"The difference here is that these are not genetically engineered cells," Dr. Hinrichs said in an interview. "These are naturally occurring T cells that are present in the tumors, grown out, and selected out for their reactivity against tumor antigens [HPV-E6 and -E7]."
The HPV-targeted tumor-infiltrating lymphocytes (TILs) are grown in the laboratory until they number in the billions and then are infused back into the patient. The women are pretreated with a lymphocyte-depleting conditioning regimen of cyclophosphamide and fludarabine (Fludara), and given aldesleukin (Proleukin), dosed to tolerance, after cell infusion.
All patients had HPV-positive cervical cancer and received a median of 81 x 10-9 T cells (range 33-159 x 10-9), Dr. Hinrichs reported.
The two women with complete responses by RECIST criteria demonstrated prolonged repopulation with the HPV-reactive T cells, detectable after 13 months in one and 6 months in the other. Two patients showed no repopulation of T cells and did not respond to treatment.
The most common severe adverse events seen with the therapy were the hematologic toxicities of the conditioning regimen, which occurred in all nine patients, Dr. Hinrichs said in an interview. Five patients had febrile neutropenia and six had infections, primarily positive blood cultures that were treated with antibiotics. All toxicities were completely reversible, and since it’s a one-time therapy, they were better tolerated than if they were repeated in cycles like traditional chemotherapy infusions, he observed.
Though encouraging, Dr. Hinrichs and others urged caution in interpreting these early data. Dr. Steven O’Day, with the University of Southern California, Los Angeles, said it’s costly and labor intensive to gather and manipulate cells and that questions remain about how to make the process more efficient, the therapy less toxic, and to determine whether cells could possibly be manipulated in vivo.
"There’re many questions, but the science is exciting, and it’s giving us an opportunity to direct the immune system against a cancer that traditionally isn’t seen by the immune system very well at all," he said. "So there are lots more to come."
Dr. Hinrichs said they plan to expand the study to 35 women to better define the response rate and that HPV-TIL is also being tested in a separate cohort of patients with noncervical HPV-positive cancers like oropharyngeal, anal, vulvar, and vaginal cancer. Physicians interested in enrolling patients should contact the National Institutes of Health. Patient referrals should be directed to June Kryk ([email protected], 301-451-1929) or Linda Williams ([email protected], 301-402-4124).
The study was supported by the National Cancer Institute, National Institutes of Health. The authors and Dr. Dizon reported no financial disclosures.
CHICAGO – A small study with just nine patients is sparking enormous hope after demonstrating for the first time that immunotherapy using adoptive T-cell therapy can induce complete remission in metastatic cervical cancer.
A single infusion of human papillomavirus (HPV)-targeted T-cell therapy induced complete responses in two women. A third woman had a partial response, with tumor shrinkage of 39% lasting 3 months.
Follow-up performed during the last week of the two women with complete responses showed no sign of disease 15 and 22 months after treatment.
"This study provides proof of principle that an immunotherapy can induce regression of cervical cancer, and that adoptive T-cell therapy can mediate regression of an epithelial cancer," said lead study author Dr. Christian S. Hinrichs, an investigator with the National Cancer Institute.
Cervical cancer harbors attractive targets for immunotherapy in the HPV E6 and E7 oncoproteins, but clinical trials of immunotherapy in this disease have thus far been disappointing.
The goal with vaccines against HPV is to reduce the future incidence of cervical cancer. But new therapies for advanced-stage disease are desperately needed because chemotherapy is not curative and rarely provides durable palliation, he said during a press briefing at the annual meeting of the American Society of Clinical Oncology.
He noted that one of the patients with a complete response had been previously treated with three different combination cytotoxic chemotherapy regimens for her HPV-16–positive squamous cell carcinoma, while the other had aggressive HPV-18–positive adenocarcinoma that had spread to the pelvis and distant sites despite chemoradiation. Both women were only 36 years old.
The best treatment we have commits women to chemotherapy and/or a biologic for the rest of their lives, which is no more than 2 years for most of the young women being treated, commented Dr. Don S. Dizon, director of the Oncology Sexual Health Clinic at the Massachusetts General Hospital Cancer Center, Boston.
"If all the academic centers can standardize this approach and identify the patients most likely to benefit, we could really reduce the deaths from this disease," he said.
Method
Research using adoptive T-cell therapy (ACT) in epithelial cancers, however, has been limited. ACT has been shown to induce dramatic, complete durable regression of melanoma and certain B-cell malignancies through use of T cells genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARS).
"The difference here is that these are not genetically engineered cells," Dr. Hinrichs said in an interview. "These are naturally occurring T cells that are present in the tumors, grown out, and selected out for their reactivity against tumor antigens [HPV-E6 and -E7]."
The HPV-targeted tumor-infiltrating lymphocytes (TILs) are grown in the laboratory until they number in the billions and then are infused back into the patient. The women are pretreated with a lymphocyte-depleting conditioning regimen of cyclophosphamide and fludarabine (Fludara), and given aldesleukin (Proleukin), dosed to tolerance, after cell infusion.
All patients had HPV-positive cervical cancer and received a median of 81 x 10-9 T cells (range 33-159 x 10-9), Dr. Hinrichs reported.
The two women with complete responses by RECIST criteria demonstrated prolonged repopulation with the HPV-reactive T cells, detectable after 13 months in one and 6 months in the other. Two patients showed no repopulation of T cells and did not respond to treatment.
The most common severe adverse events seen with the therapy were the hematologic toxicities of the conditioning regimen, which occurred in all nine patients, Dr. Hinrichs said in an interview. Five patients had febrile neutropenia and six had infections, primarily positive blood cultures that were treated with antibiotics. All toxicities were completely reversible, and since it’s a one-time therapy, they were better tolerated than if they were repeated in cycles like traditional chemotherapy infusions, he observed.
Though encouraging, Dr. Hinrichs and others urged caution in interpreting these early data. Dr. Steven O’Day, with the University of Southern California, Los Angeles, said it’s costly and labor intensive to gather and manipulate cells and that questions remain about how to make the process more efficient, the therapy less toxic, and to determine whether cells could possibly be manipulated in vivo.
"There’re many questions, but the science is exciting, and it’s giving us an opportunity to direct the immune system against a cancer that traditionally isn’t seen by the immune system very well at all," he said. "So there are lots more to come."
Dr. Hinrichs said they plan to expand the study to 35 women to better define the response rate and that HPV-TIL is also being tested in a separate cohort of patients with noncervical HPV-positive cancers like oropharyngeal, anal, vulvar, and vaginal cancer. Physicians interested in enrolling patients should contact the National Institutes of Health. Patient referrals should be directed to June Kryk ([email protected], 301-451-1929) or Linda Williams ([email protected], 301-402-4124).
The study was supported by the National Cancer Institute, National Institutes of Health. The authors and Dr. Dizon reported no financial disclosures.
AT THE ASCO ANNUAL MEETING 2014
Key clinical point: Immunotherapy using adoptive T-cell therapy can induce complete remission in metastatic cervical cancer.
Major finding: An infusion of HPV-targeted T-cell therapy induced two complete responses and one partial response.
Data source: A phase II study in nine women with metastatic cervical cancer.
Disclosures: The study was supported by the National Cancer Institute, the National Institutes of Health. The authors and Dr. Dizon reported no financial disclosures.
VIDEO: New option arises for young women with hormone-sensitive breast cancer
CHICAGO – The aromatase inhibitor exemestane is more effective than tamoxifen in preventing breast cancer recurrence in premenopausal women also receiving ovarian function suppression as adjuvant treatment for hormone-sensitive early breast cancer.
These results, taken from a combined analysis of the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) studies, were presented in a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology.
Click here for our interview with study cochair Dr. Olivia Pagani, breast unit clinical director at the Oncology Institute of Southern Switzerland in Bellinzona.
The trials were supported by the International Breast Cancer Study Group, Pfizer, Ipsen, and the National Cancer Institute. Dr. Pagani reports research support from Ipsen and Pfizer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The aromatase inhibitor exemestane is more effective than tamoxifen in preventing breast cancer recurrence in premenopausal women also receiving ovarian function suppression as adjuvant treatment for hormone-sensitive early breast cancer.
These results, taken from a combined analysis of the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) studies, were presented in a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology.
Click here for our interview with study cochair Dr. Olivia Pagani, breast unit clinical director at the Oncology Institute of Southern Switzerland in Bellinzona.
The trials were supported by the International Breast Cancer Study Group, Pfizer, Ipsen, and the National Cancer Institute. Dr. Pagani reports research support from Ipsen and Pfizer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The aromatase inhibitor exemestane is more effective than tamoxifen in preventing breast cancer recurrence in premenopausal women also receiving ovarian function suppression as adjuvant treatment for hormone-sensitive early breast cancer.
These results, taken from a combined analysis of the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) studies, were presented in a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology.
Click here for our interview with study cochair Dr. Olivia Pagani, breast unit clinical director at the Oncology Institute of Southern Switzerland in Bellinzona.
The trials were supported by the International Breast Cancer Study Group, Pfizer, Ipsen, and the National Cancer Institute. Dr. Pagani reports research support from Ipsen and Pfizer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASCO ANNUAL MEETING 2014
Goserelin improves fertility in HR-negative breast cancer
CHICAGO – Use of the gonadotropin-releasing hormone agonist goserelin during chemotherapy for early hormone receptor–negative breast cancer was associated with lower rates of ovarian failure and more pregnancies in the phase III POEMS study.
At 2 years, 22% of women receiving standard neoadjuvant or adjuvant chemotherapy alone and 8% of those receiving chemotherapy plus goserelin (Zoladex) experienced ovarian failure, defined as amenorrhea for the prior 6 months and follicle-stimulating hormone (FSH) in the postmenopausal range.
In logistic regression analysis that accounted for age and chemotherapy regimen, the risk of ovarian failure was reduced 70% with goserelin (odds ratio, 0.30; two-sided P = .04), Dr. Halle Moore reported at the annual meeting of the American Society of Clinical Oncology.
Risk was further reduced using the less stringent definition of ovarian failure of amenorrhea for the prior 6 months or FSH in the postmenopausal range (45% vs. 20%; OR, 0.29; P = .006).
The 2-year ovarian dysfunction rate was 33% with standard chemotherapy and 14% with chemotherapy plus goserelin (OR, 0.35; P = .03). Dysfunction was defined as amenorrhea for the prior 3 months and FSH, estradiol, and/or inhibin B levels in the postmenopausal range.
"For the 25 percent or so of women with breast cancer who are diagnosed under the age of 50, the induction of early menopause is a common and potentially devastating side effect of treatment," said Dr. Moore of the Cleveland Clinic.
Small studies have shown high rates of ovarian preservation in women with hematologic malignancies with the use of a luteinizing hormone release hormone (LHRH) analogue. Results of randomized trials in breast cancer have been mixed; the studies commonly used only return of menses as an endpoint, and few provided data on pregnancy outcomes, she said.
The intergroup POEMS/S0230 (Prevention of Early Menopause Study) randomly assigned 257 premenopausal women, aged 18-49 years, with operable stage I-IIIA estrogen or progesterone receptor–negative breast cancer to curative-intent standard cyclophosphamide containing neoadjuvant or adjuvant chemotherapy alone or with subcutaneous injections of goserelin 3.6 mg every 4 weeks starting at least 1 week prior to the first chemotherapy dose and ending within 2 weeks of the final dose. The average age of the groups was 38.7 and 37.6 years, respectively.
The study was closed prior to full accrual of the target 416 patients, with 218 women evaluable for pregnancy and survival outcomes and 135 for ovarian failure.
In all, 18 of 113 evaluable controls and 25 of evaluable 105 women given goserelin reported attempting pregnancy, with 12 and 22 women, respectively, becoming pregnant over the 5-year study period (OR, 2.45; P = .03), Dr. Moore said.
Compared with controls, women given goserelin were twice as likely to have a successful delivery (8 vs. 16; OR, 2.51; P = .05) and to have a successful delivery or an ongoing pregnancy at the time of the analysis (10 vs. 19; OR, 2.45; P = .04).
Twelve babies were born to women on chemotherapy alone and 18 to those given goserelin, with 3 and 5 pregnancies, respectively, ongoing.
Importantly, there was no evidence goserelin increased adverse pregnancy events such as miscarriage (5 controls vs. 4 goserelin), elective termination (3 vs. 2), and delivery complications (2 vs. 2), she said.
Grade II-IV endocrine toxicity was reported in 24% of the chemotherapy-alone arm and 48% of the goserelin arm (P = .006). One grade IV thromboembolic event occurred with goserelin, Dr. Moore said. The most common added toxicities with goserelin were hot flashes, mood changes, vaginal dryness, and headache.
A planned exploratory analysis revealed that 89% of women on goserelin versus 78% on chemotherapy alone were disease-free at 4 years, with a hazard ratio of 0.47 after controlling for age and regimen (P = .04) and 0.49 after further adjusting for cancer stage (P = .04).
Overall survival at 4 years was 92% with goserelin and 82% with chemotherapy alone, with hazard ratios of 0.45 (P = .06) and 0.43 (P = .05), respectively.
The favorable survival outcomes with the addition of goserelin are intriguing and reassuring regarding the safety of the approach, Dr. Moore said. One possible explanation for the finding is that there are a high number of LHRH receptors on hormone receptor–negative breast cancers.
"Premenopausal women beginning curative-intent chemotherapy should consider this new option to prevent premature ovarian failure," she concluded.
Discussant Dr. Sharon Giordano, chair of health services research at the University of Texas MD Anderson Cancer Center in Houston, praised POEMS for providing pregnancy information and reassuring outcome data, but said there were several limitations. The most worrisome of these was missing endpoint data for 38% of participants. The study was also hampered by early close and low accrual, and excluded women with more than 10% estrogen or progesterone receptor positivity.
"I don’t think we can consider these results definitive," she said. "Having said that, and with these caveats and recognizing the uncertainty, I would be comfortable offering goserelin to my young patients with estrogen receptor–negative breast cancer who desire to preserve fertility or prevent premature menopause."
The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, maker of goserelin. Dr. Giordano reported no relevant disclosures.
CHICAGO – Use of the gonadotropin-releasing hormone agonist goserelin during chemotherapy for early hormone receptor–negative breast cancer was associated with lower rates of ovarian failure and more pregnancies in the phase III POEMS study.
At 2 years, 22% of women receiving standard neoadjuvant or adjuvant chemotherapy alone and 8% of those receiving chemotherapy plus goserelin (Zoladex) experienced ovarian failure, defined as amenorrhea for the prior 6 months and follicle-stimulating hormone (FSH) in the postmenopausal range.
In logistic regression analysis that accounted for age and chemotherapy regimen, the risk of ovarian failure was reduced 70% with goserelin (odds ratio, 0.30; two-sided P = .04), Dr. Halle Moore reported at the annual meeting of the American Society of Clinical Oncology.
Risk was further reduced using the less stringent definition of ovarian failure of amenorrhea for the prior 6 months or FSH in the postmenopausal range (45% vs. 20%; OR, 0.29; P = .006).
The 2-year ovarian dysfunction rate was 33% with standard chemotherapy and 14% with chemotherapy plus goserelin (OR, 0.35; P = .03). Dysfunction was defined as amenorrhea for the prior 3 months and FSH, estradiol, and/or inhibin B levels in the postmenopausal range.
"For the 25 percent or so of women with breast cancer who are diagnosed under the age of 50, the induction of early menopause is a common and potentially devastating side effect of treatment," said Dr. Moore of the Cleveland Clinic.
Small studies have shown high rates of ovarian preservation in women with hematologic malignancies with the use of a luteinizing hormone release hormone (LHRH) analogue. Results of randomized trials in breast cancer have been mixed; the studies commonly used only return of menses as an endpoint, and few provided data on pregnancy outcomes, she said.
The intergroup POEMS/S0230 (Prevention of Early Menopause Study) randomly assigned 257 premenopausal women, aged 18-49 years, with operable stage I-IIIA estrogen or progesterone receptor–negative breast cancer to curative-intent standard cyclophosphamide containing neoadjuvant or adjuvant chemotherapy alone or with subcutaneous injections of goserelin 3.6 mg every 4 weeks starting at least 1 week prior to the first chemotherapy dose and ending within 2 weeks of the final dose. The average age of the groups was 38.7 and 37.6 years, respectively.
The study was closed prior to full accrual of the target 416 patients, with 218 women evaluable for pregnancy and survival outcomes and 135 for ovarian failure.
In all, 18 of 113 evaluable controls and 25 of evaluable 105 women given goserelin reported attempting pregnancy, with 12 and 22 women, respectively, becoming pregnant over the 5-year study period (OR, 2.45; P = .03), Dr. Moore said.
Compared with controls, women given goserelin were twice as likely to have a successful delivery (8 vs. 16; OR, 2.51; P = .05) and to have a successful delivery or an ongoing pregnancy at the time of the analysis (10 vs. 19; OR, 2.45; P = .04).
Twelve babies were born to women on chemotherapy alone and 18 to those given goserelin, with 3 and 5 pregnancies, respectively, ongoing.
Importantly, there was no evidence goserelin increased adverse pregnancy events such as miscarriage (5 controls vs. 4 goserelin), elective termination (3 vs. 2), and delivery complications (2 vs. 2), she said.
Grade II-IV endocrine toxicity was reported in 24% of the chemotherapy-alone arm and 48% of the goserelin arm (P = .006). One grade IV thromboembolic event occurred with goserelin, Dr. Moore said. The most common added toxicities with goserelin were hot flashes, mood changes, vaginal dryness, and headache.
A planned exploratory analysis revealed that 89% of women on goserelin versus 78% on chemotherapy alone were disease-free at 4 years, with a hazard ratio of 0.47 after controlling for age and regimen (P = .04) and 0.49 after further adjusting for cancer stage (P = .04).
Overall survival at 4 years was 92% with goserelin and 82% with chemotherapy alone, with hazard ratios of 0.45 (P = .06) and 0.43 (P = .05), respectively.
The favorable survival outcomes with the addition of goserelin are intriguing and reassuring regarding the safety of the approach, Dr. Moore said. One possible explanation for the finding is that there are a high number of LHRH receptors on hormone receptor–negative breast cancers.
"Premenopausal women beginning curative-intent chemotherapy should consider this new option to prevent premature ovarian failure," she concluded.
Discussant Dr. Sharon Giordano, chair of health services research at the University of Texas MD Anderson Cancer Center in Houston, praised POEMS for providing pregnancy information and reassuring outcome data, but said there were several limitations. The most worrisome of these was missing endpoint data for 38% of participants. The study was also hampered by early close and low accrual, and excluded women with more than 10% estrogen or progesterone receptor positivity.
"I don’t think we can consider these results definitive," she said. "Having said that, and with these caveats and recognizing the uncertainty, I would be comfortable offering goserelin to my young patients with estrogen receptor–negative breast cancer who desire to preserve fertility or prevent premature menopause."
The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, maker of goserelin. Dr. Giordano reported no relevant disclosures.
CHICAGO – Use of the gonadotropin-releasing hormone agonist goserelin during chemotherapy for early hormone receptor–negative breast cancer was associated with lower rates of ovarian failure and more pregnancies in the phase III POEMS study.
At 2 years, 22% of women receiving standard neoadjuvant or adjuvant chemotherapy alone and 8% of those receiving chemotherapy plus goserelin (Zoladex) experienced ovarian failure, defined as amenorrhea for the prior 6 months and follicle-stimulating hormone (FSH) in the postmenopausal range.
In logistic regression analysis that accounted for age and chemotherapy regimen, the risk of ovarian failure was reduced 70% with goserelin (odds ratio, 0.30; two-sided P = .04), Dr. Halle Moore reported at the annual meeting of the American Society of Clinical Oncology.
Risk was further reduced using the less stringent definition of ovarian failure of amenorrhea for the prior 6 months or FSH in the postmenopausal range (45% vs. 20%; OR, 0.29; P = .006).
The 2-year ovarian dysfunction rate was 33% with standard chemotherapy and 14% with chemotherapy plus goserelin (OR, 0.35; P = .03). Dysfunction was defined as amenorrhea for the prior 3 months and FSH, estradiol, and/or inhibin B levels in the postmenopausal range.
"For the 25 percent or so of women with breast cancer who are diagnosed under the age of 50, the induction of early menopause is a common and potentially devastating side effect of treatment," said Dr. Moore of the Cleveland Clinic.
Small studies have shown high rates of ovarian preservation in women with hematologic malignancies with the use of a luteinizing hormone release hormone (LHRH) analogue. Results of randomized trials in breast cancer have been mixed; the studies commonly used only return of menses as an endpoint, and few provided data on pregnancy outcomes, she said.
The intergroup POEMS/S0230 (Prevention of Early Menopause Study) randomly assigned 257 premenopausal women, aged 18-49 years, with operable stage I-IIIA estrogen or progesterone receptor–negative breast cancer to curative-intent standard cyclophosphamide containing neoadjuvant or adjuvant chemotherapy alone or with subcutaneous injections of goserelin 3.6 mg every 4 weeks starting at least 1 week prior to the first chemotherapy dose and ending within 2 weeks of the final dose. The average age of the groups was 38.7 and 37.6 years, respectively.
The study was closed prior to full accrual of the target 416 patients, with 218 women evaluable for pregnancy and survival outcomes and 135 for ovarian failure.
In all, 18 of 113 evaluable controls and 25 of evaluable 105 women given goserelin reported attempting pregnancy, with 12 and 22 women, respectively, becoming pregnant over the 5-year study period (OR, 2.45; P = .03), Dr. Moore said.
Compared with controls, women given goserelin were twice as likely to have a successful delivery (8 vs. 16; OR, 2.51; P = .05) and to have a successful delivery or an ongoing pregnancy at the time of the analysis (10 vs. 19; OR, 2.45; P = .04).
Twelve babies were born to women on chemotherapy alone and 18 to those given goserelin, with 3 and 5 pregnancies, respectively, ongoing.
Importantly, there was no evidence goserelin increased adverse pregnancy events such as miscarriage (5 controls vs. 4 goserelin), elective termination (3 vs. 2), and delivery complications (2 vs. 2), she said.
Grade II-IV endocrine toxicity was reported in 24% of the chemotherapy-alone arm and 48% of the goserelin arm (P = .006). One grade IV thromboembolic event occurred with goserelin, Dr. Moore said. The most common added toxicities with goserelin were hot flashes, mood changes, vaginal dryness, and headache.
A planned exploratory analysis revealed that 89% of women on goserelin versus 78% on chemotherapy alone were disease-free at 4 years, with a hazard ratio of 0.47 after controlling for age and regimen (P = .04) and 0.49 after further adjusting for cancer stage (P = .04).
Overall survival at 4 years was 92% with goserelin and 82% with chemotherapy alone, with hazard ratios of 0.45 (P = .06) and 0.43 (P = .05), respectively.
The favorable survival outcomes with the addition of goserelin are intriguing and reassuring regarding the safety of the approach, Dr. Moore said. One possible explanation for the finding is that there are a high number of LHRH receptors on hormone receptor–negative breast cancers.
"Premenopausal women beginning curative-intent chemotherapy should consider this new option to prevent premature ovarian failure," she concluded.
Discussant Dr. Sharon Giordano, chair of health services research at the University of Texas MD Anderson Cancer Center in Houston, praised POEMS for providing pregnancy information and reassuring outcome data, but said there were several limitations. The most worrisome of these was missing endpoint data for 38% of participants. The study was also hampered by early close and low accrual, and excluded women with more than 10% estrogen or progesterone receptor positivity.
"I don’t think we can consider these results definitive," she said. "Having said that, and with these caveats and recognizing the uncertainty, I would be comfortable offering goserelin to my young patients with estrogen receptor–negative breast cancer who desire to preserve fertility or prevent premature menopause."
The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, maker of goserelin. Dr. Giordano reported no relevant disclosures.
AT THE ASCO ANNUAL MEETING 2014
Key clinical point: Goserelin may be offered to young patients with hormone receptor–negative breast cancer who desire to preserve fertility or prevent premature menopause.
Major finding: The risk of ovarian failure was reduced 70% with goserelin (odds ratio, 0.30; two-sided P = .04).
Data source: A phase III randomized trial in 257 premenopausal women with hormone receptor–negative breast cancer.
Disclosures: The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, maker of goserelin. Dr. Giordano reported no relevant disclosures.
VIDEO: Ramucirumab helps prolong advanced lung cancer survival
CHICAGO – Adding the recently approved stomach cancer drug, ramucirumab (Cyramza) to docetaxel reduced the risk of death in second-line, non–small cell lung cancer by 14% in the phase III REVEL study.
This is the first therapy in roughly a decade to improve the outcome of lung cancer patients in the second-line setting, according to study author Dr. Maurice Perol, head of thoracic oncology at Cancer Research Center of Lyon, France.
In addition, the recombinant human monoclonal antibody showed benefits in nonsquamous carcinoma as well as the squamous subtype, where treatments are limited.
Still, the median survival gain of just 1.4 months did not impress all at the annual meeting of the American Society of Clinical Oncology, where the study was highlighted in a press briefing before its formal presentation Monday June 2.
To hear Dr. Perol wade through the data and controversy, listen to our interview here.
The study was supported by ImClone, a subsidiary of Eli Lilly, which markets ramucirumab. Dr. Perol reported serving as a consultant or advisor with Lilly, Pfizer, Roche, Boehringer Ingelheim, and Genentech.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Adding the recently approved stomach cancer drug, ramucirumab (Cyramza) to docetaxel reduced the risk of death in second-line, non–small cell lung cancer by 14% in the phase III REVEL study.
This is the first therapy in roughly a decade to improve the outcome of lung cancer patients in the second-line setting, according to study author Dr. Maurice Perol, head of thoracic oncology at Cancer Research Center of Lyon, France.
In addition, the recombinant human monoclonal antibody showed benefits in nonsquamous carcinoma as well as the squamous subtype, where treatments are limited.
Still, the median survival gain of just 1.4 months did not impress all at the annual meeting of the American Society of Clinical Oncology, where the study was highlighted in a press briefing before its formal presentation Monday June 2.
To hear Dr. Perol wade through the data and controversy, listen to our interview here.
The study was supported by ImClone, a subsidiary of Eli Lilly, which markets ramucirumab. Dr. Perol reported serving as a consultant or advisor with Lilly, Pfizer, Roche, Boehringer Ingelheim, and Genentech.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Adding the recently approved stomach cancer drug, ramucirumab (Cyramza) to docetaxel reduced the risk of death in second-line, non–small cell lung cancer by 14% in the phase III REVEL study.
This is the first therapy in roughly a decade to improve the outcome of lung cancer patients in the second-line setting, according to study author Dr. Maurice Perol, head of thoracic oncology at Cancer Research Center of Lyon, France.
In addition, the recombinant human monoclonal antibody showed benefits in nonsquamous carcinoma as well as the squamous subtype, where treatments are limited.
Still, the median survival gain of just 1.4 months did not impress all at the annual meeting of the American Society of Clinical Oncology, where the study was highlighted in a press briefing before its formal presentation Monday June 2.
To hear Dr. Perol wade through the data and controversy, listen to our interview here.
The study was supported by ImClone, a subsidiary of Eli Lilly, which markets ramucirumab. Dr. Perol reported serving as a consultant or advisor with Lilly, Pfizer, Roche, Boehringer Ingelheim, and Genentech.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ASCO ANNUAL MEETING 2014
VIDEO: Investigational combo stalls progression in recurrent ovarian cancer
CHICAGO – Combining two oral investigational agents, cediranib and olaparib, significantly delayed progression in recurrent ovarian cancer from 9 months with olaparib alone to 17.7 months in a phase II study.
This is the first time this strategy of coupling a PARP (poly ADP ribose polymerase) inhibitor (olaparib) with an antiangiogenesis drug (cediranib) has ever been tested in a clinical trial for ovarian cancer.
If validated, the targeted drug combination could potentially provide women with recurrent ovarian cancer an alternative to standard chemotherapy, according to lead author Dr. Joyce F. Liu of Dana-Farber Cancer Institute, Boston.
We caught up with Dr. Liu at this year’s annual meeting of the American Society of Clinical Oncology, where the study was formally presented.
Dr. Liu reported having no financial disclosures. The study was supported by the National Cancer Institute and National Institutes of Health.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Combining two oral investigational agents, cediranib and olaparib, significantly delayed progression in recurrent ovarian cancer from 9 months with olaparib alone to 17.7 months in a phase II study.
This is the first time this strategy of coupling a PARP (poly ADP ribose polymerase) inhibitor (olaparib) with an antiangiogenesis drug (cediranib) has ever been tested in a clinical trial for ovarian cancer.
If validated, the targeted drug combination could potentially provide women with recurrent ovarian cancer an alternative to standard chemotherapy, according to lead author Dr. Joyce F. Liu of Dana-Farber Cancer Institute, Boston.
We caught up with Dr. Liu at this year’s annual meeting of the American Society of Clinical Oncology, where the study was formally presented.
Dr. Liu reported having no financial disclosures. The study was supported by the National Cancer Institute and National Institutes of Health.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Combining two oral investigational agents, cediranib and olaparib, significantly delayed progression in recurrent ovarian cancer from 9 months with olaparib alone to 17.7 months in a phase II study.
This is the first time this strategy of coupling a PARP (poly ADP ribose polymerase) inhibitor (olaparib) with an antiangiogenesis drug (cediranib) has ever been tested in a clinical trial for ovarian cancer.
If validated, the targeted drug combination could potentially provide women with recurrent ovarian cancer an alternative to standard chemotherapy, according to lead author Dr. Joyce F. Liu of Dana-Farber Cancer Institute, Boston.
We caught up with Dr. Liu at this year’s annual meeting of the American Society of Clinical Oncology, where the study was formally presented.
Dr. Liu reported having no financial disclosures. The study was supported by the National Cancer Institute and National Institutes of Health.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ASCO ANNUAL MEETING 2014
VIDEO: Less frequent zoledronic acid is safe, retains efficacy
CHICAGO – Women with breast cancer and bone metastasis can safely scale back the frequency of their zoledronic acid infusions from every 4 weeks to every 12 weeks without a loss in efficacy*, according to results of the phase III OPTIMIZE 2 trial.
Notably, the dreaded bisphosphonate side effect of osteonecrosis of the jaw was seen in two patients in the monthly arm, but none of those in the every-3-month treatment arm.
The findings apply only to breast cancer patients who’ve completed at least 1 year of monthly zoledronic acid therapy, according to study author Dr. Gabriel N. Hortobagyi, a professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston.
In an interview with us at the 50th anniversary of the American Society of Clinical Oncology, this past ASCO president said that the findings from this late-breaking abstract study will have implications for the costs of cancer care and possibly for patients with other cancers.
Dr. Hortobagyi reported consultant or advisory roles and research funding with Novartis, the study sponsor. Several coauthors are employees of or have leadership positions with Novartis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Correction, 5/31/2014: An earlier version of this article misstated the duration of their zoledronic acid infusion treatments.
CHICAGO – Women with breast cancer and bone metastasis can safely scale back the frequency of their zoledronic acid infusions from every 4 weeks to every 12 weeks without a loss in efficacy*, according to results of the phase III OPTIMIZE 2 trial.
Notably, the dreaded bisphosphonate side effect of osteonecrosis of the jaw was seen in two patients in the monthly arm, but none of those in the every-3-month treatment arm.
The findings apply only to breast cancer patients who’ve completed at least 1 year of monthly zoledronic acid therapy, according to study author Dr. Gabriel N. Hortobagyi, a professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston.
In an interview with us at the 50th anniversary of the American Society of Clinical Oncology, this past ASCO president said that the findings from this late-breaking abstract study will have implications for the costs of cancer care and possibly for patients with other cancers.
Dr. Hortobagyi reported consultant or advisory roles and research funding with Novartis, the study sponsor. Several coauthors are employees of or have leadership positions with Novartis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Correction, 5/31/2014: An earlier version of this article misstated the duration of their zoledronic acid infusion treatments.
CHICAGO – Women with breast cancer and bone metastasis can safely scale back the frequency of their zoledronic acid infusions from every 4 weeks to every 12 weeks without a loss in efficacy*, according to results of the phase III OPTIMIZE 2 trial.
Notably, the dreaded bisphosphonate side effect of osteonecrosis of the jaw was seen in two patients in the monthly arm, but none of those in the every-3-month treatment arm.
The findings apply only to breast cancer patients who’ve completed at least 1 year of monthly zoledronic acid therapy, according to study author Dr. Gabriel N. Hortobagyi, a professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston.
In an interview with us at the 50th anniversary of the American Society of Clinical Oncology, this past ASCO president said that the findings from this late-breaking abstract study will have implications for the costs of cancer care and possibly for patients with other cancers.
Dr. Hortobagyi reported consultant or advisory roles and research funding with Novartis, the study sponsor. Several coauthors are employees of or have leadership positions with Novartis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Correction, 5/31/2014: An earlier version of this article misstated the duration of their zoledronic acid infusion treatments.
AT THE ASCO ANNUAL MEETING 2014
VIDEO: Goserelin helps dodge ovarian failure in HR-negative breast cancer
CHICAGO – Adding the gonadotropin-releasing hormone agonist goserelin (Zoladex) to adjuvant or neoadjuvant chemotherapy boosted fertility prospects in premenopausal women with early-stage hormone-receptor–negative breast cancer.
Not only did goserelin reduce by 70% the risk of ovarian failure, a common consequence of chemotherapy, but the monthly injections also offered an intriguing boost in disease-free and overall survival.
Lead author of the intergroup POEMS (Prevention of Early Menopause Study) Dr. Halle Moore of the Cleveland Clinic spoke with us about the late-breaking trial at the annual meeting of the American Society of Clinical Oncology.
Click here to hear more about these practice-changing results.
The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, the maker of goserelin.
Correction 5/31/14: An earlier version of this article carried a headline that misstated the cancer type.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Adding the gonadotropin-releasing hormone agonist goserelin (Zoladex) to adjuvant or neoadjuvant chemotherapy boosted fertility prospects in premenopausal women with early-stage hormone-receptor–negative breast cancer.
Not only did goserelin reduce by 70% the risk of ovarian failure, a common consequence of chemotherapy, but the monthly injections also offered an intriguing boost in disease-free and overall survival.
Lead author of the intergroup POEMS (Prevention of Early Menopause Study) Dr. Halle Moore of the Cleveland Clinic spoke with us about the late-breaking trial at the annual meeting of the American Society of Clinical Oncology.
Click here to hear more about these practice-changing results.
The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, the maker of goserelin.
Correction 5/31/14: An earlier version of this article carried a headline that misstated the cancer type.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Adding the gonadotropin-releasing hormone agonist goserelin (Zoladex) to adjuvant or neoadjuvant chemotherapy boosted fertility prospects in premenopausal women with early-stage hormone-receptor–negative breast cancer.
Not only did goserelin reduce by 70% the risk of ovarian failure, a common consequence of chemotherapy, but the monthly injections also offered an intriguing boost in disease-free and overall survival.
Lead author of the intergroup POEMS (Prevention of Early Menopause Study) Dr. Halle Moore of the Cleveland Clinic spoke with us about the late-breaking trial at the annual meeting of the American Society of Clinical Oncology.
Click here to hear more about these practice-changing results.
The study was supported by the National Institutes of Health. Dr. Moore reported no disclosures; three coauthors have financial ties with AstraZeneca, the maker of goserelin.
Correction 5/31/14: An earlier version of this article carried a headline that misstated the cancer type.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASCO 2014
Liver cancer without cirrhosis surprisingly common: Is NAFLD the cause?
CHICAGO – A full 13% of patients diagnosed with hepatocellular carcinoma did not have underlying cirrhosis in a national sample of 1,500 veterans.
Although hepatocellular carcinoma (HCC) in patients with cirrhosis typically arises against a background of alcohol abuse or hepatitis C virus infection, this entity was strongly associated with nonalcoholic fatty liver disease (NAFLD) and idiopathic HCC.
"While this represents a small proportion, this poses a logistical problem for HCC surveillance, given the large population with NAFLD and no real identifying features of who is going to develop HCC," Dr. Sahil Mittal said at the annual Digestive Disease Week.
Despite a threefold increase in HCC in the United States over the last 3 decades and emerging evidence for NAFLD presenting in the absence of cirrhosis, this is the first study to assess the prevalence and risk factors for HCC without cirrhosis in a national sample of HCC patients, he said.
The investigators, led by Dr. Hashem B. El-Serag, section chief, gastroenterology and hepatology, Baylor College of Medicine, Houston, performed a chart review of 1,500 veterans with a confirmed diagnosis of HCC randomly selected between 2005 and 2011. Of these, cirrhosis was absent in 43 (3%), highly improbable in 151 (10%), and definite in 1,201 (80%), with the diagnosis unclear because of insufficient data in 105 (7%).
As expected, HCC patients with cirrhosis were significantly more likely than those with no or probable no cirrhosis to abuse alcohol (84% vs. 67.4% vs. 63.6%; P less than .01) and to have hepatitis C infection (72.2% vs. 42% vs. 44.4%; P less than .01), said Dr. Mittal, also with Baylor’s College of Medicine.
Hepatitis B infection was similar in all three groups (5% vs. 4.7% vs. 2%).
In contrast, NAFLD was more common in patients with no or probably no cirrhosis than in those with cirrhosis (14% vs. 20.5% vs. 5.8%; P less than .01), as was idiopathic HCC (18.6% vs. 27.8% vs. 8.2%; P less than .01), he said.
"NAFLD is associated with a significantly increased risk of HCC in the absence of cirrhosis, compared with hepatitis C or alcohol," he said.
With regard to clinical factors, sex and race did not differ between groups. However, the no and probably no cirrhosis patients were significantly older than were those with HCC accompanied by cirrhosis (65.5 years, vs. 69.7 years vs. 62.6 years) and significantly more likely to have comorbidities associated with metabolic syndrome, such as hypertension (88.4% vs. 86.8% vs. 72.6%), myocardial infarction (11.6% vs. 18.5% vs. 7.5%), and peripheral vascular disease (11.6% vs. 20% vs. 9.5%), Dr. Mittal reported. The differences among groups were statistically significant with P values of less than .01.
The investigators then performed logistic regression analysis to examine predictors of HCC without cirrhosis. After adjustment for confounders, they found NAFLD was more than threefold likely (odds ratio, 3.1) and idiopathic HCC more than twofold likely (OR, 2.8) in patients with HCC without cirrhosis, compared with patients with hepatitis C–related HCC.
This entity of HCC in the absence of cirrhosis was also associated with the metabolic syndrome–related comorbidities of hypertension (OR, 1.8) and myocardial infarction (OR, 1.8).
The findings suggest that the risk of HCC in patients with NAFLD is increased not only because of progression to cirrhosis, but possibly through other alternative noncirrhosis pathways, Dr. Mittal said in an interview. This has important implications for understanding the pathogenesis of HCC, as well as for HCC screening in NAFLD patients.
"Due to the high prevalence of NAFLD in the general population, conventional screening by ultrasonography may not be a feasible strategy, especially if one cannot rely on cirrhosis as the main predisposing lesion to HCC," he said. "Studies are needed to identify risk factors and biomarkers that can identify NAFLD patients at higher risk of developing HCC. Future research is also needed to investigate the role of chemoprevention."
Dr. Mittal reported no conflicting interests. Lead author Dr. El-Serag reported consulting fees and grant/research support from Gilead Sciences.
CHICAGO – A full 13% of patients diagnosed with hepatocellular carcinoma did not have underlying cirrhosis in a national sample of 1,500 veterans.
Although hepatocellular carcinoma (HCC) in patients with cirrhosis typically arises against a background of alcohol abuse or hepatitis C virus infection, this entity was strongly associated with nonalcoholic fatty liver disease (NAFLD) and idiopathic HCC.
"While this represents a small proportion, this poses a logistical problem for HCC surveillance, given the large population with NAFLD and no real identifying features of who is going to develop HCC," Dr. Sahil Mittal said at the annual Digestive Disease Week.
Despite a threefold increase in HCC in the United States over the last 3 decades and emerging evidence for NAFLD presenting in the absence of cirrhosis, this is the first study to assess the prevalence and risk factors for HCC without cirrhosis in a national sample of HCC patients, he said.
The investigators, led by Dr. Hashem B. El-Serag, section chief, gastroenterology and hepatology, Baylor College of Medicine, Houston, performed a chart review of 1,500 veterans with a confirmed diagnosis of HCC randomly selected between 2005 and 2011. Of these, cirrhosis was absent in 43 (3%), highly improbable in 151 (10%), and definite in 1,201 (80%), with the diagnosis unclear because of insufficient data in 105 (7%).
As expected, HCC patients with cirrhosis were significantly more likely than those with no or probable no cirrhosis to abuse alcohol (84% vs. 67.4% vs. 63.6%; P less than .01) and to have hepatitis C infection (72.2% vs. 42% vs. 44.4%; P less than .01), said Dr. Mittal, also with Baylor’s College of Medicine.
Hepatitis B infection was similar in all three groups (5% vs. 4.7% vs. 2%).
In contrast, NAFLD was more common in patients with no or probably no cirrhosis than in those with cirrhosis (14% vs. 20.5% vs. 5.8%; P less than .01), as was idiopathic HCC (18.6% vs. 27.8% vs. 8.2%; P less than .01), he said.
"NAFLD is associated with a significantly increased risk of HCC in the absence of cirrhosis, compared with hepatitis C or alcohol," he said.
With regard to clinical factors, sex and race did not differ between groups. However, the no and probably no cirrhosis patients were significantly older than were those with HCC accompanied by cirrhosis (65.5 years, vs. 69.7 years vs. 62.6 years) and significantly more likely to have comorbidities associated with metabolic syndrome, such as hypertension (88.4% vs. 86.8% vs. 72.6%), myocardial infarction (11.6% vs. 18.5% vs. 7.5%), and peripheral vascular disease (11.6% vs. 20% vs. 9.5%), Dr. Mittal reported. The differences among groups were statistically significant with P values of less than .01.
The investigators then performed logistic regression analysis to examine predictors of HCC without cirrhosis. After adjustment for confounders, they found NAFLD was more than threefold likely (odds ratio, 3.1) and idiopathic HCC more than twofold likely (OR, 2.8) in patients with HCC without cirrhosis, compared with patients with hepatitis C–related HCC.
This entity of HCC in the absence of cirrhosis was also associated with the metabolic syndrome–related comorbidities of hypertension (OR, 1.8) and myocardial infarction (OR, 1.8).
The findings suggest that the risk of HCC in patients with NAFLD is increased not only because of progression to cirrhosis, but possibly through other alternative noncirrhosis pathways, Dr. Mittal said in an interview. This has important implications for understanding the pathogenesis of HCC, as well as for HCC screening in NAFLD patients.
"Due to the high prevalence of NAFLD in the general population, conventional screening by ultrasonography may not be a feasible strategy, especially if one cannot rely on cirrhosis as the main predisposing lesion to HCC," he said. "Studies are needed to identify risk factors and biomarkers that can identify NAFLD patients at higher risk of developing HCC. Future research is also needed to investigate the role of chemoprevention."
Dr. Mittal reported no conflicting interests. Lead author Dr. El-Serag reported consulting fees and grant/research support from Gilead Sciences.
CHICAGO – A full 13% of patients diagnosed with hepatocellular carcinoma did not have underlying cirrhosis in a national sample of 1,500 veterans.
Although hepatocellular carcinoma (HCC) in patients with cirrhosis typically arises against a background of alcohol abuse or hepatitis C virus infection, this entity was strongly associated with nonalcoholic fatty liver disease (NAFLD) and idiopathic HCC.
"While this represents a small proportion, this poses a logistical problem for HCC surveillance, given the large population with NAFLD and no real identifying features of who is going to develop HCC," Dr. Sahil Mittal said at the annual Digestive Disease Week.
Despite a threefold increase in HCC in the United States over the last 3 decades and emerging evidence for NAFLD presenting in the absence of cirrhosis, this is the first study to assess the prevalence and risk factors for HCC without cirrhosis in a national sample of HCC patients, he said.
The investigators, led by Dr. Hashem B. El-Serag, section chief, gastroenterology and hepatology, Baylor College of Medicine, Houston, performed a chart review of 1,500 veterans with a confirmed diagnosis of HCC randomly selected between 2005 and 2011. Of these, cirrhosis was absent in 43 (3%), highly improbable in 151 (10%), and definite in 1,201 (80%), with the diagnosis unclear because of insufficient data in 105 (7%).
As expected, HCC patients with cirrhosis were significantly more likely than those with no or probable no cirrhosis to abuse alcohol (84% vs. 67.4% vs. 63.6%; P less than .01) and to have hepatitis C infection (72.2% vs. 42% vs. 44.4%; P less than .01), said Dr. Mittal, also with Baylor’s College of Medicine.
Hepatitis B infection was similar in all three groups (5% vs. 4.7% vs. 2%).
In contrast, NAFLD was more common in patients with no or probably no cirrhosis than in those with cirrhosis (14% vs. 20.5% vs. 5.8%; P less than .01), as was idiopathic HCC (18.6% vs. 27.8% vs. 8.2%; P less than .01), he said.
"NAFLD is associated with a significantly increased risk of HCC in the absence of cirrhosis, compared with hepatitis C or alcohol," he said.
With regard to clinical factors, sex and race did not differ between groups. However, the no and probably no cirrhosis patients were significantly older than were those with HCC accompanied by cirrhosis (65.5 years, vs. 69.7 years vs. 62.6 years) and significantly more likely to have comorbidities associated with metabolic syndrome, such as hypertension (88.4% vs. 86.8% vs. 72.6%), myocardial infarction (11.6% vs. 18.5% vs. 7.5%), and peripheral vascular disease (11.6% vs. 20% vs. 9.5%), Dr. Mittal reported. The differences among groups were statistically significant with P values of less than .01.
The investigators then performed logistic regression analysis to examine predictors of HCC without cirrhosis. After adjustment for confounders, they found NAFLD was more than threefold likely (odds ratio, 3.1) and idiopathic HCC more than twofold likely (OR, 2.8) in patients with HCC without cirrhosis, compared with patients with hepatitis C–related HCC.
This entity of HCC in the absence of cirrhosis was also associated with the metabolic syndrome–related comorbidities of hypertension (OR, 1.8) and myocardial infarction (OR, 1.8).
The findings suggest that the risk of HCC in patients with NAFLD is increased not only because of progression to cirrhosis, but possibly through other alternative noncirrhosis pathways, Dr. Mittal said in an interview. This has important implications for understanding the pathogenesis of HCC, as well as for HCC screening in NAFLD patients.
"Due to the high prevalence of NAFLD in the general population, conventional screening by ultrasonography may not be a feasible strategy, especially if one cannot rely on cirrhosis as the main predisposing lesion to HCC," he said. "Studies are needed to identify risk factors and biomarkers that can identify NAFLD patients at higher risk of developing HCC. Future research is also needed to investigate the role of chemoprevention."
Dr. Mittal reported no conflicting interests. Lead author Dr. El-Serag reported consulting fees and grant/research support from Gilead Sciences.
AT DDW 2014
Key clinical point: A significant proportion of NAFLD-related HCC patients have no cirrhosis at presentation, so clinicians need to maintain a high index of suspicion.
Major finding: Up to 13% of patients with HCC in the United States may not have underlying cirrhosis.
Data source: A retrospective cohort study of 1,500 veterans with HCC.
Disclosures: Dr. Mittal reported no conflicting interests. Lead author Dr. El-Serag reported consulting fees and grant/research support from Gilead Sciences.
Glucosamine, chondroitin combo found equal to celecoxib for severe knee OA pain
PARIS – A fixed-dose combination of glucosamine and chondroitin sulfate was as good as the cyclo-oxygenase-2 inhibitor celecoxib in relieving moderate to severe knee pain in patients with knee osteoarthritis in the double-blind, noninferiority MOVES trial.
Side effect profiles and tolerability were also similar with glucosamine/chondroitin (Droglican) and celecoxib (Celebrex), with 51% of patients overall experiencing treatment-emergent adverse events, Dr. Marc Hochberg reported at the World Congress on Osteoarthritis.
"In a group that is either contraindicated or relatively contraindicated to celecoxib, you get similar efficacy [with Droglican] at 6 months," he said in an interview.
Dr. Hochberg noted that the phase IV (MOVES) Multicentric Osteoarthritis Intervention Study enrolled patients who were consistent with the European label for celecoxib, meaning that those with prior coronary artery disease or peripheral artery disease were excluded, as were those with unstable diabetes or uncontrolled hypertension.
MOVES was designed to extend the findings of the GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial), which suggested in exploratory analyses that combination 1,500 mg daily glucosamine and 1,200 mg daily chondroitin sulfate was effective in the subgroup with moderate to severe knee osteoarthritis pain, but that either agent alone or in combination was not effective in reducing osteoarthritis knee pain in the overall cohort (N. Engl. J. Med. 2006;354:795-808).
MOVES randomly assigned 606 patients in a double-blind, double-dummy fashion to receive either two capsules of Droglican (250 mg glucosamine and 200 mg chondroitin sulfate) three times daily or celecoxib 200 mg plus five placebo capsules per day. Two-thirds of patients (62.6%) had Kellgren-Lawrence grade 2 radiological changes, and 84% were female. Their mean age was 62.7 years.
At 180 days, the mean WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores in the Droglican and celecoxib groups improved from 372 and 370.6, respectively, to 185.8 and 184.7.
This corresponds to a mean difference of 1.11 units (95% confidence interval, –21.99-19.76; P = .917), which met the noninferiority margin, according to Dr. Hochberg, head of rheumatology and clinical immunology, University of Maryland, Baltimore.The results remained robust in sensitivity analyses.
There also were no significant differences between the two groups in the absolute improvement in the WOMAC stiffness and function scales and the five individual items of the WOMAC pain scale at 6 months, Dr. Hochberg reported at the meeting, sponsored by the Osteoarthritis Research Society International.
Dr. Hochberg reported no conflicts. His coauthors were employees or on the steering committee for Bioiberica, the study sponsor and maker of Droglican.
PARIS – A fixed-dose combination of glucosamine and chondroitin sulfate was as good as the cyclo-oxygenase-2 inhibitor celecoxib in relieving moderate to severe knee pain in patients with knee osteoarthritis in the double-blind, noninferiority MOVES trial.
Side effect profiles and tolerability were also similar with glucosamine/chondroitin (Droglican) and celecoxib (Celebrex), with 51% of patients overall experiencing treatment-emergent adverse events, Dr. Marc Hochberg reported at the World Congress on Osteoarthritis.
"In a group that is either contraindicated or relatively contraindicated to celecoxib, you get similar efficacy [with Droglican] at 6 months," he said in an interview.
Dr. Hochberg noted that the phase IV (MOVES) Multicentric Osteoarthritis Intervention Study enrolled patients who were consistent with the European label for celecoxib, meaning that those with prior coronary artery disease or peripheral artery disease were excluded, as were those with unstable diabetes or uncontrolled hypertension.
MOVES was designed to extend the findings of the GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial), which suggested in exploratory analyses that combination 1,500 mg daily glucosamine and 1,200 mg daily chondroitin sulfate was effective in the subgroup with moderate to severe knee osteoarthritis pain, but that either agent alone or in combination was not effective in reducing osteoarthritis knee pain in the overall cohort (N. Engl. J. Med. 2006;354:795-808).
MOVES randomly assigned 606 patients in a double-blind, double-dummy fashion to receive either two capsules of Droglican (250 mg glucosamine and 200 mg chondroitin sulfate) three times daily or celecoxib 200 mg plus five placebo capsules per day. Two-thirds of patients (62.6%) had Kellgren-Lawrence grade 2 radiological changes, and 84% were female. Their mean age was 62.7 years.
At 180 days, the mean WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores in the Droglican and celecoxib groups improved from 372 and 370.6, respectively, to 185.8 and 184.7.
This corresponds to a mean difference of 1.11 units (95% confidence interval, –21.99-19.76; P = .917), which met the noninferiority margin, according to Dr. Hochberg, head of rheumatology and clinical immunology, University of Maryland, Baltimore.The results remained robust in sensitivity analyses.
There also were no significant differences between the two groups in the absolute improvement in the WOMAC stiffness and function scales and the five individual items of the WOMAC pain scale at 6 months, Dr. Hochberg reported at the meeting, sponsored by the Osteoarthritis Research Society International.
Dr. Hochberg reported no conflicts. His coauthors were employees or on the steering committee for Bioiberica, the study sponsor and maker of Droglican.
PARIS – A fixed-dose combination of glucosamine and chondroitin sulfate was as good as the cyclo-oxygenase-2 inhibitor celecoxib in relieving moderate to severe knee pain in patients with knee osteoarthritis in the double-blind, noninferiority MOVES trial.
Side effect profiles and tolerability were also similar with glucosamine/chondroitin (Droglican) and celecoxib (Celebrex), with 51% of patients overall experiencing treatment-emergent adverse events, Dr. Marc Hochberg reported at the World Congress on Osteoarthritis.
"In a group that is either contraindicated or relatively contraindicated to celecoxib, you get similar efficacy [with Droglican] at 6 months," he said in an interview.
Dr. Hochberg noted that the phase IV (MOVES) Multicentric Osteoarthritis Intervention Study enrolled patients who were consistent with the European label for celecoxib, meaning that those with prior coronary artery disease or peripheral artery disease were excluded, as were those with unstable diabetes or uncontrolled hypertension.
MOVES was designed to extend the findings of the GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial), which suggested in exploratory analyses that combination 1,500 mg daily glucosamine and 1,200 mg daily chondroitin sulfate was effective in the subgroup with moderate to severe knee osteoarthritis pain, but that either agent alone or in combination was not effective in reducing osteoarthritis knee pain in the overall cohort (N. Engl. J. Med. 2006;354:795-808).
MOVES randomly assigned 606 patients in a double-blind, double-dummy fashion to receive either two capsules of Droglican (250 mg glucosamine and 200 mg chondroitin sulfate) three times daily or celecoxib 200 mg plus five placebo capsules per day. Two-thirds of patients (62.6%) had Kellgren-Lawrence grade 2 radiological changes, and 84% were female. Their mean age was 62.7 years.
At 180 days, the mean WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores in the Droglican and celecoxib groups improved from 372 and 370.6, respectively, to 185.8 and 184.7.
This corresponds to a mean difference of 1.11 units (95% confidence interval, –21.99-19.76; P = .917), which met the noninferiority margin, according to Dr. Hochberg, head of rheumatology and clinical immunology, University of Maryland, Baltimore.The results remained robust in sensitivity analyses.
There also were no significant differences between the two groups in the absolute improvement in the WOMAC stiffness and function scales and the five individual items of the WOMAC pain scale at 6 months, Dr. Hochberg reported at the meeting, sponsored by the Osteoarthritis Research Society International.
Dr. Hochberg reported no conflicts. His coauthors were employees or on the steering committee for Bioiberica, the study sponsor and maker of Droglican.
AT OARSI 2014
Key clinical point: Patients with moderate to severe knee OA pain who do not have prior coronary artery disease or peripheral artery disease or unstable diabetes or uncontrolled hypertension have similar reductions in pain with either celecoxib 200 mg daily or a combination of 250 mg glucosamine and 200 mg chondroitin sulfate three times daily.
Major finding: Mean WOMAC scores improved in the Droglican and celecoxib groups from 372 and 370.6 at baseline to 185.8 and 184.7 at 180 days.
Data source: A prospective, double-blind, double-dummy trial in 606 patients with moderate to severe knee OA pain.
Disclosures: Dr. Hochberg reported no conflicts. His coauthors were employees or on the steering committee for Bioiberica, the study sponsor and maker of Droglican.
FISH panel may improve Barrett’s surveillance
CHICAGO – Fluorescence in situ hybridization testing for aneuploidy and loss of the tumor suppressor gene P16 can be useful in predicting progression to high-grade dysplasia and adenocarcinoma in patients with nondysplastic Barrett’s esophagus.
Adding these genetic biomarkers to the clinical risk factors of age and Barrett’s esophagus (BE) segment length provides for an even more robust prediction tool, Dr. Margriet R. Timmer said at the annual Digestive Disease Week.
This conclusion is based on a prospective, multicenter cohort study involving 428 patients with nondysplastic BE. The average age of the patients was 59 years and maximum BE length 3 cm.
Fluorescence in situ hybridization (FISH) analysis was used to detect genetic abnormalities on endoscopic cytology brushes from all patients. The FISH panel included probes for six candidate biomarkers: the tumor suppressor genes P16 and P53, the oncogenes MYC, HER-2/neu, and 20q, as well as aneuploidy.
After a median follow-up of 45 months, 22 patients had histologic progression after review by two expert pathologists: 13 cases of high-grade dysplasia (HGD) and 9 cases of esophageal adenocarcinoma (EAC).
The rate of progression to HGD/EAC was 1.09% per patient-year and 0.65% per patient-year for EAC, said Dr. Timmer of the Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Univariable analysis revealed that P16 loss (hazard ratio, 2.56; P = .03) and aneuploidy (HR, 2.66; P = .04) significantly predicted progression, as did increasing age (HR, 1.06; P = .008) and longer BE length (HR, 1.15; P = .017).
None of the other biomarkers or clinical factors such as male sex, body mass index, tobacco use, family history of BE or EAC, or years of BE were significant.
A prediction model was then created using the significant predictors. The C statistic, which takes into account specificity and sensitivity, was 0.68 for the basic model that included only age and BE length, but this improved significantly to 0.73 when the biomarkers were added, she said.
Based on the prediction model, 236 patients were considered high risk and 192 patients were low risk.
Importantly, 5-year progression-free survival was significantly lower in the high-risk group than in the low-risk group (93.6% vs. 98.4%; P = .001), Dr. Timmer noted.
Session cochair Roy Wong of Walter Reed Army Medical Center, Washington, said in an interview that "intellectually, the concept is terrific," but that clinicians will need a specific risk cutoff to apply the findings to an individual patient in the community setting and that overall survival data would strengthen the results.
The study authors acknowledged that FISH testing is still costly and that they have yet to use it in the clinical setting. One major advantage of FISH, however, is that it can be applied to cytology specimens that can be easily obtained during upper endoscopy by brushing the entire Barrett’s segment, thereby overcoming the potential problem of biopsy sampling error, Dr. Timmer said.
The study was funded by grants from KWF Kanderbestrijding (the Dutch Cancer Society), NOW (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek), Fonds NutsOhra, Gut Club, and Abbott Molecular. Dr. Timmer and her coauthors reported no financial disclosures.
CHICAGO – Fluorescence in situ hybridization testing for aneuploidy and loss of the tumor suppressor gene P16 can be useful in predicting progression to high-grade dysplasia and adenocarcinoma in patients with nondysplastic Barrett’s esophagus.
Adding these genetic biomarkers to the clinical risk factors of age and Barrett’s esophagus (BE) segment length provides for an even more robust prediction tool, Dr. Margriet R. Timmer said at the annual Digestive Disease Week.
This conclusion is based on a prospective, multicenter cohort study involving 428 patients with nondysplastic BE. The average age of the patients was 59 years and maximum BE length 3 cm.
Fluorescence in situ hybridization (FISH) analysis was used to detect genetic abnormalities on endoscopic cytology brushes from all patients. The FISH panel included probes for six candidate biomarkers: the tumor suppressor genes P16 and P53, the oncogenes MYC, HER-2/neu, and 20q, as well as aneuploidy.
After a median follow-up of 45 months, 22 patients had histologic progression after review by two expert pathologists: 13 cases of high-grade dysplasia (HGD) and 9 cases of esophageal adenocarcinoma (EAC).
The rate of progression to HGD/EAC was 1.09% per patient-year and 0.65% per patient-year for EAC, said Dr. Timmer of the Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Univariable analysis revealed that P16 loss (hazard ratio, 2.56; P = .03) and aneuploidy (HR, 2.66; P = .04) significantly predicted progression, as did increasing age (HR, 1.06; P = .008) and longer BE length (HR, 1.15; P = .017).
None of the other biomarkers or clinical factors such as male sex, body mass index, tobacco use, family history of BE or EAC, or years of BE were significant.
A prediction model was then created using the significant predictors. The C statistic, which takes into account specificity and sensitivity, was 0.68 for the basic model that included only age and BE length, but this improved significantly to 0.73 when the biomarkers were added, she said.
Based on the prediction model, 236 patients were considered high risk and 192 patients were low risk.
Importantly, 5-year progression-free survival was significantly lower in the high-risk group than in the low-risk group (93.6% vs. 98.4%; P = .001), Dr. Timmer noted.
Session cochair Roy Wong of Walter Reed Army Medical Center, Washington, said in an interview that "intellectually, the concept is terrific," but that clinicians will need a specific risk cutoff to apply the findings to an individual patient in the community setting and that overall survival data would strengthen the results.
The study authors acknowledged that FISH testing is still costly and that they have yet to use it in the clinical setting. One major advantage of FISH, however, is that it can be applied to cytology specimens that can be easily obtained during upper endoscopy by brushing the entire Barrett’s segment, thereby overcoming the potential problem of biopsy sampling error, Dr. Timmer said.
The study was funded by grants from KWF Kanderbestrijding (the Dutch Cancer Society), NOW (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek), Fonds NutsOhra, Gut Club, and Abbott Molecular. Dr. Timmer and her coauthors reported no financial disclosures.
CHICAGO – Fluorescence in situ hybridization testing for aneuploidy and loss of the tumor suppressor gene P16 can be useful in predicting progression to high-grade dysplasia and adenocarcinoma in patients with nondysplastic Barrett’s esophagus.
Adding these genetic biomarkers to the clinical risk factors of age and Barrett’s esophagus (BE) segment length provides for an even more robust prediction tool, Dr. Margriet R. Timmer said at the annual Digestive Disease Week.
This conclusion is based on a prospective, multicenter cohort study involving 428 patients with nondysplastic BE. The average age of the patients was 59 years and maximum BE length 3 cm.
Fluorescence in situ hybridization (FISH) analysis was used to detect genetic abnormalities on endoscopic cytology brushes from all patients. The FISH panel included probes for six candidate biomarkers: the tumor suppressor genes P16 and P53, the oncogenes MYC, HER-2/neu, and 20q, as well as aneuploidy.
After a median follow-up of 45 months, 22 patients had histologic progression after review by two expert pathologists: 13 cases of high-grade dysplasia (HGD) and 9 cases of esophageal adenocarcinoma (EAC).
The rate of progression to HGD/EAC was 1.09% per patient-year and 0.65% per patient-year for EAC, said Dr. Timmer of the Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Univariable analysis revealed that P16 loss (hazard ratio, 2.56; P = .03) and aneuploidy (HR, 2.66; P = .04) significantly predicted progression, as did increasing age (HR, 1.06; P = .008) and longer BE length (HR, 1.15; P = .017).
None of the other biomarkers or clinical factors such as male sex, body mass index, tobacco use, family history of BE or EAC, or years of BE were significant.
A prediction model was then created using the significant predictors. The C statistic, which takes into account specificity and sensitivity, was 0.68 for the basic model that included only age and BE length, but this improved significantly to 0.73 when the biomarkers were added, she said.
Based on the prediction model, 236 patients were considered high risk and 192 patients were low risk.
Importantly, 5-year progression-free survival was significantly lower in the high-risk group than in the low-risk group (93.6% vs. 98.4%; P = .001), Dr. Timmer noted.
Session cochair Roy Wong of Walter Reed Army Medical Center, Washington, said in an interview that "intellectually, the concept is terrific," but that clinicians will need a specific risk cutoff to apply the findings to an individual patient in the community setting and that overall survival data would strengthen the results.
The study authors acknowledged that FISH testing is still costly and that they have yet to use it in the clinical setting. One major advantage of FISH, however, is that it can be applied to cytology specimens that can be easily obtained during upper endoscopy by brushing the entire Barrett’s segment, thereby overcoming the potential problem of biopsy sampling error, Dr. Timmer said.
The study was funded by grants from KWF Kanderbestrijding (the Dutch Cancer Society), NOW (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek), Fonds NutsOhra, Gut Club, and Abbott Molecular. Dr. Timmer and her coauthors reported no financial disclosures.
AT DDW 2014
Key clinical point: Assessing aneuploidy and P16 as well as age and BE length can be useful in stratifying patients with Barrett’s esophagus into high- and low-risk disease categories to improve the efficacy of surveillance programs.
Major finding: P16 loss (hazard ratio, 2.56; P = .03) and aneuploidy (HR, 2.66; P = .04), increasing age (HR, 1.06; P = .008), and longer BE length (HR, 1.15; P = .017) predicted progression.
Data source: A prospective study of 428 patients with nondysplastic Barrett’s esophagus.
Disclosures: The study was funded by grants from KWF Kanderbestrijding (the Dutch Cancer Society), NOW (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek), Fonds NutsOhra, Gut Club, and Abbott Molecular. Dr. Timmer and her coauthors reported no financial disclosures.
