Roxanne Nelson

Stereotactic radiosurgery (SRS) is being used increasingly for brain metastases to prevent central nervous system (CNS) toxicity, and new findings published in Clinical Genitourinary Cancer demonstrate that it is a highly effective procedure for brain metastases from renal cell carcinoma (RCC).

In this study, the 1-year local control rate was more than 90% and durability of control was up to 2 years. SRS appears to be the most efficacious for smaller metastases, while escalated dosing or fractionation are needed to effectively treat larger lesions.

In metastatic RCC, the incidence of brain metastases is as high as 15%, and while surgical resection is associated with an improved survival compared with whole brain radiotherapy alone, for patients who are not candidates for resection, SRS is an alternative option. For this study, the authors sought to determine outcomes after treatment with SRS for brain metastases in 268 patients with metastatic RCC who were treated between 2006 and 2015 at a single institution.

Of this group, 38 patients were identified with brain metastases and a total of 243 lesions were treated with SRS, reported Zabi Wardak, MD, and his associates.

The median lesion size was 0.6 cm (0.2-3.1) and patients received a median SRS treatment dose of 18 Gy (12-24). The median age of patients was 65 years and the most common histology was clear cell RCC. Three quarters (74%) of patients received only one GammaKnife session, with a median number of two lesions treated at each session. The most common intracranial location for metastases was the frontal lobe (39% of lesions) followed by the parietal and temporal lobes (15% of lesions). The median size of treated metastases was 0.6 cm (0.2-3.1), reported Dr. Wardak, of the University of Texas UT Southwestern Medical Center, Dallas, and his associates.

At 1 year, local control rates were 91.8% (95% confidence interval, 85.7-95.4) and at 2 years, 86.1% (77.1-91.7). The median overall survival after a diagnosis of brain metastases was 13.8 months (95% CI, 8.1-28.0), with a 1-year survival of 57.5% (95% CI, 40.2-71.4). For patients with a single brain metastasis, 1-year overall survival was 56.3% (95% CI, 29.5-76.2) and for those with multiple lesions, 59.1% (95% CI, 36.1-76.2).

“Patients with multiple brain metastases (greater than five lesions) from RCC did not have a worse survival and should be considered for SRS to achieve intracranial tumor control while avoiding neurological decline,” wrote Dr. Wardak and his associates.

Coauthor James Brugarolas is supported by a grant from the National Institutes of Health. No other study funding was disclosed. The other authors have no disclosures.

SOURCE: Wardak Z et al. Clin Genitourin Cancer. 2018 Nov 20. doi: 10.1016/j.clgc.2018.11.006.

Stereotactic radiosurgery (SRS) is being used increasingly for brain metastases to prevent central nervous system (CNS) toxicity, and new findings published in Clinical Genitourinary Cancer demonstrate that it is a highly effective procedure for brain metastases from renal cell carcinoma (RCC).

In this study, the 1-year local control rate was more than 90% and durability of control was up to 2 years. SRS appears to be the most efficacious for smaller metastases, while escalated dosing or fractionation are needed to effectively treat larger lesions.

In metastatic RCC, the incidence of brain metastases is as high as 15%, and while surgical resection is associated with an improved survival compared with whole brain radiotherapy alone, for patients who are not candidates for resection, SRS is an alternative option. For this study, the authors sought to determine outcomes after treatment with SRS for brain metastases in 268 patients with metastatic RCC who were treated between 2006 and 2015 at a single institution.

Of this group, 38 patients were identified with brain metastases and a total of 243 lesions were treated with SRS, reported Zabi Wardak, MD, and his associates.

The median lesion size was 0.6 cm (0.2-3.1) and patients received a median SRS treatment dose of 18 Gy (12-24). The median age of patients was 65 years and the most common histology was clear cell RCC. Three quarters (74%) of patients received only one GammaKnife session, with a median number of two lesions treated at each session. The most common intracranial location for metastases was the frontal lobe (39% of lesions) followed by the parietal and temporal lobes (15% of lesions). The median size of treated metastases was 0.6 cm (0.2-3.1), reported Dr. Wardak, of the University of Texas UT Southwestern Medical Center, Dallas, and his associates.

At 1 year, local control rates were 91.8% (95% confidence interval, 85.7-95.4) and at 2 years, 86.1% (77.1-91.7). The median overall survival after a diagnosis of brain metastases was 13.8 months (95% CI, 8.1-28.0), with a 1-year survival of 57.5% (95% CI, 40.2-71.4). For patients with a single brain metastasis, 1-year overall survival was 56.3% (95% CI, 29.5-76.2) and for those with multiple lesions, 59.1% (95% CI, 36.1-76.2).

“Patients with multiple brain metastases (greater than five lesions) from RCC did not have a worse survival and should be considered for SRS to achieve intracranial tumor control while avoiding neurological decline,” wrote Dr. Wardak and his associates.

Coauthor James Brugarolas is supported by a grant from the National Institutes of Health. No other study funding was disclosed. The other authors have no disclosures.

SOURCE: Wardak Z et al. Clin Genitourin Cancer. 2018 Nov 20. doi: 10.1016/j.clgc.2018.11.006.

Stereotactic radiosurgery (SRS) is being used increasingly for brain metastases to prevent central nervous system (CNS) toxicity, and new findings published in Clinical Genitourinary Cancer demonstrate that it is a highly effective procedure for brain metastases from renal cell carcinoma (RCC).

In this study, the 1-year local control rate was more than 90% and durability of control was up to 2 years. SRS appears to be the most efficacious for smaller metastases, while escalated dosing or fractionation are needed to effectively treat larger lesions.

In metastatic RCC, the incidence of brain metastases is as high as 15%, and while surgical resection is associated with an improved survival compared with whole brain radiotherapy alone, for patients who are not candidates for resection, SRS is an alternative option. For this study, the authors sought to determine outcomes after treatment with SRS for brain metastases in 268 patients with metastatic RCC who were treated between 2006 and 2015 at a single institution.

Of this group, 38 patients were identified with brain metastases and a total of 243 lesions were treated with SRS, reported Zabi Wardak, MD, and his associates.

The median lesion size was 0.6 cm (0.2-3.1) and patients received a median SRS treatment dose of 18 Gy (12-24). The median age of patients was 65 years and the most common histology was clear cell RCC. Three quarters (74%) of patients received only one GammaKnife session, with a median number of two lesions treated at each session. The most common intracranial location for metastases was the frontal lobe (39% of lesions) followed by the parietal and temporal lobes (15% of lesions). The median size of treated metastases was 0.6 cm (0.2-3.1), reported Dr. Wardak, of the University of Texas UT Southwestern Medical Center, Dallas, and his associates.

At 1 year, local control rates were 91.8% (95% confidence interval, 85.7-95.4) and at 2 years, 86.1% (77.1-91.7). The median overall survival after a diagnosis of brain metastases was 13.8 months (95% CI, 8.1-28.0), with a 1-year survival of 57.5% (95% CI, 40.2-71.4). For patients with a single brain metastasis, 1-year overall survival was 56.3% (95% CI, 29.5-76.2) and for those with multiple lesions, 59.1% (95% CI, 36.1-76.2).

“Patients with multiple brain metastases (greater than five lesions) from RCC did not have a worse survival and should be considered for SRS to achieve intracranial tumor control while avoiding neurological decline,” wrote Dr. Wardak and his associates.

Coauthor James Brugarolas is supported by a grant from the National Institutes of Health. No other study funding was disclosed. The other authors have no disclosures.

SOURCE: Wardak Z et al. Clin Genitourin Cancer. 2018 Nov 20. doi: 10.1016/j.clgc.2018.11.006.

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

Alveolar soft part sarcoma (ASPS) has often proven to be resistant to conventional doxorubicin-based chemotherapy, but tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) may provide new treatment strategies for this rare type of sarcoma, according to a literature review.

A rare, translocation-driven sarcoma of the soft tissues, ASPS often affects young adults and is characterized by indolent behavior and early metastasis. Despite its resistance to chemotherapy, studies indicate that survival is often prolonged in patients with metastatic disease. The literature has shown 5-year survival rates at about 60%, and this percentage has remained fairly consistent for the past 3 decades.

Luca Paoluzzi, MD, of New York University, and Robert G. Maki, MD, PhD, of Hofstra University, Hempstead, N.Y., reviewed the literature from 1952 to March 2018, in order to gain a better understanding of ASPS and the opportunities “for the translation of such knowledge into clinical practice,” they wrote in JAMA.

From a therapeutic standpoint, ASPS is characterized by sensitivity to vascular endothelial growth factor receptor–predominant TKIs, compared with other soft tissue sarcomas (STS), and recent data have emphasized that it is responsive to new immunotherapy regimens including ICIs. Pazopanib is currently the only agent that has received regulatory approval for use in STS refractory to other treatments and it appears to have consistent activity in metastatic ASPS. Management of ASPS generally also involves surgical resection and/or systemic treatment for metastatic disease. Conventional agents such as anthracycline-based chemotherapy have demonstrated a poor response rate lower than 10%, and while a complete resection may be curative, metastases are common and can occur years after resection of the primary tumor.

Conversely, ICIs “represent a promising area of drug development in ASPS; the data to date are limited but encouraging,” wrote Dr. Paoluzzi and Dr. Maki.

They pointed to one study that included 50 patients with sarcoma with 14 different subtypes of STS who were enrolled in immunotherapy trials conducted at the University of Texas MD Anderson Cancer Center, Houston. There were two pretreated patients with ASPS (two to four prior lines) in the cohort who received antiprogrammed death-ligand 1–based therapy, and achieved a partial response bordering on a complete response that lasted 8 and 12 months. An additional two patients achieved stable disease.

Another paper, presented at the 2017 Connective Tissue Oncology Society annual meeting, presented preliminary data from a phase 2 study that showed four of nine evaluable patients with ASPS treated with the TKI axitinib, combined with pembrolizumab, achieved a partial response. Three others had stable disease.

“Pathway-driven basket trials facilitate the enrollment of patients with such uncommon cancers and should provide valuable information regarding a second type of immune responsiveness to ICIs, one that is not a function of high tumor mutational burden,” the authors concluded.

No outside funding sources were reported. Dr. Maki reported receiving consultant fees from numerous sources and research support to New York University from Immune Design, Immunocore, Eli Lilly, Presage Biosciences, TRACON Pharmaceuticals, SARC, Regeneron, and Genentech. No other conflicts were reported.

SOURCE: Paoluzzi L et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4490.

Alveolar soft part sarcoma (ASPS) has often proven to be resistant to conventional doxorubicin-based chemotherapy, but tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) may provide new treatment strategies for this rare type of sarcoma, according to a literature review.

A rare, translocation-driven sarcoma of the soft tissues, ASPS often affects young adults and is characterized by indolent behavior and early metastasis. Despite its resistance to chemotherapy, studies indicate that survival is often prolonged in patients with metastatic disease. The literature has shown 5-year survival rates at about 60%, and this percentage has remained fairly consistent for the past 3 decades.

Luca Paoluzzi, MD, of New York University, and Robert G. Maki, MD, PhD, of Hofstra University, Hempstead, N.Y., reviewed the literature from 1952 to March 2018, in order to gain a better understanding of ASPS and the opportunities “for the translation of such knowledge into clinical practice,” they wrote in JAMA.

From a therapeutic standpoint, ASPS is characterized by sensitivity to vascular endothelial growth factor receptor–predominant TKIs, compared with other soft tissue sarcomas (STS), and recent data have emphasized that it is responsive to new immunotherapy regimens including ICIs. Pazopanib is currently the only agent that has received regulatory approval for use in STS refractory to other treatments and it appears to have consistent activity in metastatic ASPS. Management of ASPS generally also involves surgical resection and/or systemic treatment for metastatic disease. Conventional agents such as anthracycline-based chemotherapy have demonstrated a poor response rate lower than 10%, and while a complete resection may be curative, metastases are common and can occur years after resection of the primary tumor.

Conversely, ICIs “represent a promising area of drug development in ASPS; the data to date are limited but encouraging,” wrote Dr. Paoluzzi and Dr. Maki.

They pointed to one study that included 50 patients with sarcoma with 14 different subtypes of STS who were enrolled in immunotherapy trials conducted at the University of Texas MD Anderson Cancer Center, Houston. There were two pretreated patients with ASPS (two to four prior lines) in the cohort who received antiprogrammed death-ligand 1–based therapy, and achieved a partial response bordering on a complete response that lasted 8 and 12 months. An additional two patients achieved stable disease.

Another paper, presented at the 2017 Connective Tissue Oncology Society annual meeting, presented preliminary data from a phase 2 study that showed four of nine evaluable patients with ASPS treated with the TKI axitinib, combined with pembrolizumab, achieved a partial response. Three others had stable disease.

“Pathway-driven basket trials facilitate the enrollment of patients with such uncommon cancers and should provide valuable information regarding a second type of immune responsiveness to ICIs, one that is not a function of high tumor mutational burden,” the authors concluded.

No outside funding sources were reported. Dr. Maki reported receiving consultant fees from numerous sources and research support to New York University from Immune Design, Immunocore, Eli Lilly, Presage Biosciences, TRACON Pharmaceuticals, SARC, Regeneron, and Genentech. No other conflicts were reported.

SOURCE: Paoluzzi L et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4490.

Alveolar soft part sarcoma (ASPS) has often proven to be resistant to conventional doxorubicin-based chemotherapy, but tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) may provide new treatment strategies for this rare type of sarcoma, according to a literature review.

A rare, translocation-driven sarcoma of the soft tissues, ASPS often affects young adults and is characterized by indolent behavior and early metastasis. Despite its resistance to chemotherapy, studies indicate that survival is often prolonged in patients with metastatic disease. The literature has shown 5-year survival rates at about 60%, and this percentage has remained fairly consistent for the past 3 decades.

Luca Paoluzzi, MD, of New York University, and Robert G. Maki, MD, PhD, of Hofstra University, Hempstead, N.Y., reviewed the literature from 1952 to March 2018, in order to gain a better understanding of ASPS and the opportunities “for the translation of such knowledge into clinical practice,” they wrote in JAMA.

From a therapeutic standpoint, ASPS is characterized by sensitivity to vascular endothelial growth factor receptor–predominant TKIs, compared with other soft tissue sarcomas (STS), and recent data have emphasized that it is responsive to new immunotherapy regimens including ICIs. Pazopanib is currently the only agent that has received regulatory approval for use in STS refractory to other treatments and it appears to have consistent activity in metastatic ASPS. Management of ASPS generally also involves surgical resection and/or systemic treatment for metastatic disease. Conventional agents such as anthracycline-based chemotherapy have demonstrated a poor response rate lower than 10%, and while a complete resection may be curative, metastases are common and can occur years after resection of the primary tumor.

Conversely, ICIs “represent a promising area of drug development in ASPS; the data to date are limited but encouraging,” wrote Dr. Paoluzzi and Dr. Maki.

They pointed to one study that included 50 patients with sarcoma with 14 different subtypes of STS who were enrolled in immunotherapy trials conducted at the University of Texas MD Anderson Cancer Center, Houston. There were two pretreated patients with ASPS (two to four prior lines) in the cohort who received antiprogrammed death-ligand 1–based therapy, and achieved a partial response bordering on a complete response that lasted 8 and 12 months. An additional two patients achieved stable disease.

Another paper, presented at the 2017 Connective Tissue Oncology Society annual meeting, presented preliminary data from a phase 2 study that showed four of nine evaluable patients with ASPS treated with the TKI axitinib, combined with pembrolizumab, achieved a partial response. Three others had stable disease.

“Pathway-driven basket trials facilitate the enrollment of patients with such uncommon cancers and should provide valuable information regarding a second type of immune responsiveness to ICIs, one that is not a function of high tumor mutational burden,” the authors concluded.

No outside funding sources were reported. Dr. Maki reported receiving consultant fees from numerous sources and research support to New York University from Immune Design, Immunocore, Eli Lilly, Presage Biosciences, TRACON Pharmaceuticals, SARC, Regeneron, and Genentech. No other conflicts were reported.

SOURCE: Paoluzzi L et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4490.

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.

Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.

In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.

For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).

The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.

In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.

The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.

There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).

In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.

“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”

The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.

SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.

Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).

“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.

Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.

To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.

A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.

The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).

The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).

When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.

“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.

There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.

SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.

Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.

Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).

“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.

Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.

To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.

A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.

The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).

The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).

When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.

“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.

There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.

SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.

Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.

Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).

“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.

Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.

To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.

A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.

The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).

The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).

When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.

“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.

There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.

SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.

Tailored frequency-escalated prophylaxis produced good outcomes with little arthropathy among boys with hemophilia A, according to findings from a prospective study.

The potential to use smaller amounts of clotting factor concentrates (CFCs) also offers a possible cost savings, Brian M. Feldman, MD, of the Hospital for Sick Children, Toronto, and his colleagues reported in the Lancet Haematology.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Prophylactic treatment to prevent bleeding episodes and avoid long term complications using regular CFCs is very effective but also very expensive. The Canadian Hemophilia Prophylaxis Study (CHPS) began 2 decades ago with the premise that, since CFC use accounts for most of the financial burden in severe hemophilia and because primary prophylaxis is started at a very young age, the burden on both the patient and the health care system could potentially be reduced by starting prophylaxis with CFC infusions at reduced frequency intervals. The individual’s subsequent bleeding episodes would then determine how the dose and frequency could be tailored.

In the study, 56 boys between the ages of 1 and 2.5 years with severe hemophilia A from 12 Canadian centers were enrolled in the CHPS, with a median time in the study of 10.2 years. Treatment was with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once weekly prophylaxis with 50 IU/kg and then escalating in frequency with appropriate dose adjustments as needed (step 1). The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores at completion of the study.

Participants were able to stay on once a week prophylaxis, without unacceptable bleeding, until a median age of 4.5 years. At this time, boys who developed unacceptable bleeding were escalated to twice-weekly prophylaxis at 30 IU/kg (step 2). The median age for beginning alternate day prophylaxis at 25 IU/kg (step 3) was 9.9 years of age.

The median annual SHL-rFVIII use was 3,582 IU/kg at age 2 years (n = 56), 4,041 IU/kg at age 6 years (n = 53), 3,638 IU/kg at age 10 years (n = 40), and 3,663 IU/kg at 14 years of age (n = 18). Overall adherence to the tailored regimen was a median of 86%, and no treatment-related safety events were observed during the study, including central venous catheter infections.

The median use of SHL-rFVIII on the tailored frequency-escalated prophylaxis is considerably less than the 6,000 IU/kg per year used in standard prophylaxis regimens, the researchers noted.

“We have previously shown, with a formal cost-benefit analysis using the value-of-information approach, that tailored frequency escalated prophylaxis provides substantial cost-benefit in a variety of scenarios. Our results from this study lend further support to these findings,” they wrote.

The median annualized index joint bleeding rate was 0.95 per year, but 30% of the boys in the study experienced “unacceptable breakthrough bleeding” during the study.

Overall joint health was “well preserved,” according to the researchers. The median Colorado Child Physical Examination Score at the end of the CHPS was 1 (range 0-12) for the left ankle and 1 for the right ankle, with all other joints having a median score of 0.

Activities of daily living and physical function, as well as health-related quality of life were generally good, the researchers reported.

The study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and by the Bayer/Canadian Blood Services/Héma-Québec Partnership Fund. Subsequent renewals were funded by Bayer. Dr. Feldman reported grants from Bayer during the conduct of the study and grants from Baxter/Baxalta/Shire outside the submitted work. Several coauthors also report multiple relationships with industry.

SOURCE: Feldman BM et al. Lancet Haematol. 2018 May 3. doi: 10.1016/S2352-3026(18)30048-6.

Tailored frequency-escalated prophylaxis produced good outcomes with little arthropathy among boys with hemophilia A, according to findings from a prospective study.

The potential to use smaller amounts of clotting factor concentrates (CFCs) also offers a possible cost savings, Brian M. Feldman, MD, of the Hospital for Sick Children, Toronto, and his colleagues reported in the Lancet Haematology.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Prophylactic treatment to prevent bleeding episodes and avoid long term complications using regular CFCs is very effective but also very expensive. The Canadian Hemophilia Prophylaxis Study (CHPS) began 2 decades ago with the premise that, since CFC use accounts for most of the financial burden in severe hemophilia and because primary prophylaxis is started at a very young age, the burden on both the patient and the health care system could potentially be reduced by starting prophylaxis with CFC infusions at reduced frequency intervals. The individual’s subsequent bleeding episodes would then determine how the dose and frequency could be tailored.

In the study, 56 boys between the ages of 1 and 2.5 years with severe hemophilia A from 12 Canadian centers were enrolled in the CHPS, with a median time in the study of 10.2 years. Treatment was with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once weekly prophylaxis with 50 IU/kg and then escalating in frequency with appropriate dose adjustments as needed (step 1). The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores at completion of the study.

Participants were able to stay on once a week prophylaxis, without unacceptable bleeding, until a median age of 4.5 years. At this time, boys who developed unacceptable bleeding were escalated to twice-weekly prophylaxis at 30 IU/kg (step 2). The median age for beginning alternate day prophylaxis at 25 IU/kg (step 3) was 9.9 years of age.

The median annual SHL-rFVIII use was 3,582 IU/kg at age 2 years (n = 56), 4,041 IU/kg at age 6 years (n = 53), 3,638 IU/kg at age 10 years (n = 40), and 3,663 IU/kg at 14 years of age (n = 18). Overall adherence to the tailored regimen was a median of 86%, and no treatment-related safety events were observed during the study, including central venous catheter infections.

The median use of SHL-rFVIII on the tailored frequency-escalated prophylaxis is considerably less than the 6,000 IU/kg per year used in standard prophylaxis regimens, the researchers noted.

“We have previously shown, with a formal cost-benefit analysis using the value-of-information approach, that tailored frequency escalated prophylaxis provides substantial cost-benefit in a variety of scenarios. Our results from this study lend further support to these findings,” they wrote.

The median annualized index joint bleeding rate was 0.95 per year, but 30% of the boys in the study experienced “unacceptable breakthrough bleeding” during the study.

Overall joint health was “well preserved,” according to the researchers. The median Colorado Child Physical Examination Score at the end of the CHPS was 1 (range 0-12) for the left ankle and 1 for the right ankle, with all other joints having a median score of 0.

Activities of daily living and physical function, as well as health-related quality of life were generally good, the researchers reported.

The study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and by the Bayer/Canadian Blood Services/Héma-Québec Partnership Fund. Subsequent renewals were funded by Bayer. Dr. Feldman reported grants from Bayer during the conduct of the study and grants from Baxter/Baxalta/Shire outside the submitted work. Several coauthors also report multiple relationships with industry.

SOURCE: Feldman BM et al. Lancet Haematol. 2018 May 3. doi: 10.1016/S2352-3026(18)30048-6.

Tailored frequency-escalated prophylaxis produced good outcomes with little arthropathy among boys with hemophilia A, according to findings from a prospective study.

The potential to use smaller amounts of clotting factor concentrates (CFCs) also offers a possible cost savings, Brian M. Feldman, MD, of the Hospital for Sick Children, Toronto, and his colleagues reported in the Lancet Haematology.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Prophylactic treatment to prevent bleeding episodes and avoid long term complications using regular CFCs is very effective but also very expensive. The Canadian Hemophilia Prophylaxis Study (CHPS) began 2 decades ago with the premise that, since CFC use accounts for most of the financial burden in severe hemophilia and because primary prophylaxis is started at a very young age, the burden on both the patient and the health care system could potentially be reduced by starting prophylaxis with CFC infusions at reduced frequency intervals. The individual’s subsequent bleeding episodes would then determine how the dose and frequency could be tailored.

In the study, 56 boys between the ages of 1 and 2.5 years with severe hemophilia A from 12 Canadian centers were enrolled in the CHPS, with a median time in the study of 10.2 years. Treatment was with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once weekly prophylaxis with 50 IU/kg and then escalating in frequency with appropriate dose adjustments as needed (step 1). The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores at completion of the study.

Participants were able to stay on once a week prophylaxis, without unacceptable bleeding, until a median age of 4.5 years. At this time, boys who developed unacceptable bleeding were escalated to twice-weekly prophylaxis at 30 IU/kg (step 2). The median age for beginning alternate day prophylaxis at 25 IU/kg (step 3) was 9.9 years of age.

The median annual SHL-rFVIII use was 3,582 IU/kg at age 2 years (n = 56), 4,041 IU/kg at age 6 years (n = 53), 3,638 IU/kg at age 10 years (n = 40), and 3,663 IU/kg at 14 years of age (n = 18). Overall adherence to the tailored regimen was a median of 86%, and no treatment-related safety events were observed during the study, including central venous catheter infections.

The median use of SHL-rFVIII on the tailored frequency-escalated prophylaxis is considerably less than the 6,000 IU/kg per year used in standard prophylaxis regimens, the researchers noted.

“We have previously shown, with a formal cost-benefit analysis using the value-of-information approach, that tailored frequency escalated prophylaxis provides substantial cost-benefit in a variety of scenarios. Our results from this study lend further support to these findings,” they wrote.

The median annualized index joint bleeding rate was 0.95 per year, but 30% of the boys in the study experienced “unacceptable breakthrough bleeding” during the study.

Overall joint health was “well preserved,” according to the researchers. The median Colorado Child Physical Examination Score at the end of the CHPS was 1 (range 0-12) for the left ankle and 1 for the right ankle, with all other joints having a median score of 0.

Activities of daily living and physical function, as well as health-related quality of life were generally good, the researchers reported.

The study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and by the Bayer/Canadian Blood Services/Héma-Québec Partnership Fund. Subsequent renewals were funded by Bayer. Dr. Feldman reported grants from Bayer during the conduct of the study and grants from Baxter/Baxalta/Shire outside the submitted work. Several coauthors also report multiple relationships with industry.

SOURCE: Feldman BM et al. Lancet Haematol. 2018 May 3. doi: 10.1016/S2352-3026(18)30048-6.

Oral bisphosphonates may confer a protective effect against lung cancer, according to an observational study.

However, this effect was only observed among never-smokers, as there was no significant difference in lung cancer incidence between oral bisphosphonate use and nonuse in the overall study cohort, Meng-Hua Tao, PhD, of the University of North Texas Health Science Center, Fort Worth, and associates reported in Annals of Oncology.

While bisphosphonates are commonly prescribed to prevent and treat osteoporosis, research suggests that they may have a range of other benefits, such as inhibition of tumor angiogenesis and cellular proliferation, prevention of tumor-cell adhesion and invasion, and induction of tumor-cell apoptosis. Recent studies have also investigated the association between bisphosphonate use and the risk of several cancers including breast, gastrointestinal tract, endometrial, and ovarian. Additionally, a few studies have looked at the relationship between oral bisphosphonates and lung cancer risk, but results have been inconsistent.

However, previous studies had very limited information on lung cancer risk factors, such as tobacco use, and none had analyzed the potential associations between bisphosphonate use and lung cancer and how it might vary by smoking status, the authors noted.

In the current study, the relationship between oral bisphosphonates use and lung cancer risk, and its potential interaction with smoking status on lung cancer risk, was examined using a prospective cohort of 151,432 postmenopausal women enrolled in the Women’s Health Initiative during 1993-1998. At baseline and follow-up, an inventory of regularly used medications including bisphosphonates was completed.

After a mean cumulative follow-up of 13.3 years, there were 2,257 nonusers and 254 ever-users of oral bisphosphonates, and 2,511 women were diagnosed with incident lung cancer. On multivariable-adjusted analysis, the hazard ratio for lung cancer incidence after use of any type of oral bisphosphonate, compared with never-use, was not significantly different (HR = 0.91; 95% confidence interval, 0.80-1.04; P = .16).

In a subgroup analysis, the authors found that the association patterns differed between never-smokers and ever-smokers (P = .02). Among women who never smoked, oral bisphosphonate use was inversely associated with lung cancer risk in the multivariate adjusted models (HR = 0.57; 95% CI, 0.39-0.84; P less than .01), and this association was stronger when the duration of bisphosphonate usage was 1.5 years or longer (HR, 0.36; 95% CI, 0.18-0.73).

For ever-smokers, there was no association between bisphosphonate use and lung cancer risk.

When looking at lung cancer subtype, the incidences of small cell lung cancer and non–small cell lung cancer were similar in bisphosphonate users, but for never-smokers, bisphosphonate use was also associated with a lower non–small cell lung cancer risk (HR = 0.62; 95% CI, 0.41-0.92; P = .02).

“These observational study findings need to be confirmed. As the U.S. Food and Drug Administration issued safety announcements related to potential risk of long-term bisphosphonate use further studies are warranted to investigate how duration of bisphosphonate use may influence risk of lung cancer and evaluate optimal dose of oral bisphosphonates for lung cancer prevention in older women,” wrote Dr. Tao and her associates.

The study was primarily supported by a grant from the National Cancer Institute at the National Institutes of Health. Dr. Tao has no disclosures.

SOURCE: Tao MH et al. Ann Oncol. 2018 Mar 29. doi:10.1093/annonc/mdy097.

Oral bisphosphonates may confer a protective effect against lung cancer, according to an observational study.

However, this effect was only observed among never-smokers, as there was no significant difference in lung cancer incidence between oral bisphosphonate use and nonuse in the overall study cohort, Meng-Hua Tao, PhD, of the University of North Texas Health Science Center, Fort Worth, and associates reported in Annals of Oncology.

While bisphosphonates are commonly prescribed to prevent and treat osteoporosis, research suggests that they may have a range of other benefits, such as inhibition of tumor angiogenesis and cellular proliferation, prevention of tumor-cell adhesion and invasion, and induction of tumor-cell apoptosis. Recent studies have also investigated the association between bisphosphonate use and the risk of several cancers including breast, gastrointestinal tract, endometrial, and ovarian. Additionally, a few studies have looked at the relationship between oral bisphosphonates and lung cancer risk, but results have been inconsistent.

However, previous studies had very limited information on lung cancer risk factors, such as tobacco use, and none had analyzed the potential associations between bisphosphonate use and lung cancer and how it might vary by smoking status, the authors noted.

In the current study, the relationship between oral bisphosphonates use and lung cancer risk, and its potential interaction with smoking status on lung cancer risk, was examined using a prospective cohort of 151,432 postmenopausal women enrolled in the Women’s Health Initiative during 1993-1998. At baseline and follow-up, an inventory of regularly used medications including bisphosphonates was completed.

After a mean cumulative follow-up of 13.3 years, there were 2,257 nonusers and 254 ever-users of oral bisphosphonates, and 2,511 women were diagnosed with incident lung cancer. On multivariable-adjusted analysis, the hazard ratio for lung cancer incidence after use of any type of oral bisphosphonate, compared with never-use, was not significantly different (HR = 0.91; 95% confidence interval, 0.80-1.04; P = .16).

In a subgroup analysis, the authors found that the association patterns differed between never-smokers and ever-smokers (P = .02). Among women who never smoked, oral bisphosphonate use was inversely associated with lung cancer risk in the multivariate adjusted models (HR = 0.57; 95% CI, 0.39-0.84; P less than .01), and this association was stronger when the duration of bisphosphonate usage was 1.5 years or longer (HR, 0.36; 95% CI, 0.18-0.73).

For ever-smokers, there was no association between bisphosphonate use and lung cancer risk.

When looking at lung cancer subtype, the incidences of small cell lung cancer and non–small cell lung cancer were similar in bisphosphonate users, but for never-smokers, bisphosphonate use was also associated with a lower non–small cell lung cancer risk (HR = 0.62; 95% CI, 0.41-0.92; P = .02).

“These observational study findings need to be confirmed. As the U.S. Food and Drug Administration issued safety announcements related to potential risk of long-term bisphosphonate use further studies are warranted to investigate how duration of bisphosphonate use may influence risk of lung cancer and evaluate optimal dose of oral bisphosphonates for lung cancer prevention in older women,” wrote Dr. Tao and her associates.

The study was primarily supported by a grant from the National Cancer Institute at the National Institutes of Health. Dr. Tao has no disclosures.

SOURCE: Tao MH et al. Ann Oncol. 2018 Mar 29. doi:10.1093/annonc/mdy097.

Oral bisphosphonates may confer a protective effect against lung cancer, according to an observational study.

However, this effect was only observed among never-smokers, as there was no significant difference in lung cancer incidence between oral bisphosphonate use and nonuse in the overall study cohort, Meng-Hua Tao, PhD, of the University of North Texas Health Science Center, Fort Worth, and associates reported in Annals of Oncology.

While bisphosphonates are commonly prescribed to prevent and treat osteoporosis, research suggests that they may have a range of other benefits, such as inhibition of tumor angiogenesis and cellular proliferation, prevention of tumor-cell adhesion and invasion, and induction of tumor-cell apoptosis. Recent studies have also investigated the association between bisphosphonate use and the risk of several cancers including breast, gastrointestinal tract, endometrial, and ovarian. Additionally, a few studies have looked at the relationship between oral bisphosphonates and lung cancer risk, but results have been inconsistent.

However, previous studies had very limited information on lung cancer risk factors, such as tobacco use, and none had analyzed the potential associations between bisphosphonate use and lung cancer and how it might vary by smoking status, the authors noted.

In the current study, the relationship between oral bisphosphonates use and lung cancer risk, and its potential interaction with smoking status on lung cancer risk, was examined using a prospective cohort of 151,432 postmenopausal women enrolled in the Women’s Health Initiative during 1993-1998. At baseline and follow-up, an inventory of regularly used medications including bisphosphonates was completed.

After a mean cumulative follow-up of 13.3 years, there were 2,257 nonusers and 254 ever-users of oral bisphosphonates, and 2,511 women were diagnosed with incident lung cancer. On multivariable-adjusted analysis, the hazard ratio for lung cancer incidence after use of any type of oral bisphosphonate, compared with never-use, was not significantly different (HR = 0.91; 95% confidence interval, 0.80-1.04; P = .16).

In a subgroup analysis, the authors found that the association patterns differed between never-smokers and ever-smokers (P = .02). Among women who never smoked, oral bisphosphonate use was inversely associated with lung cancer risk in the multivariate adjusted models (HR = 0.57; 95% CI, 0.39-0.84; P less than .01), and this association was stronger when the duration of bisphosphonate usage was 1.5 years or longer (HR, 0.36; 95% CI, 0.18-0.73).

For ever-smokers, there was no association between bisphosphonate use and lung cancer risk.

When looking at lung cancer subtype, the incidences of small cell lung cancer and non–small cell lung cancer were similar in bisphosphonate users, but for never-smokers, bisphosphonate use was also associated with a lower non–small cell lung cancer risk (HR = 0.62; 95% CI, 0.41-0.92; P = .02).

“These observational study findings need to be confirmed. As the U.S. Food and Drug Administration issued safety announcements related to potential risk of long-term bisphosphonate use further studies are warranted to investigate how duration of bisphosphonate use may influence risk of lung cancer and evaluate optimal dose of oral bisphosphonates for lung cancer prevention in older women,” wrote Dr. Tao and her associates.

The study was primarily supported by a grant from the National Cancer Institute at the National Institutes of Health. Dr. Tao has no disclosures.

SOURCE: Tao MH et al. Ann Oncol. 2018 Mar 29. doi:10.1093/annonc/mdy097.