Will Pass

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.

In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.

An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in JAMA Oncology.

To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.

Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.

However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.

The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.

“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.

“[T]he utility of oxaliplatin in stage II CRC remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis,” the investigators concluded.

The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.


SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi: 10.1001/jamaoncol.2019.6486.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force (USMSTF) on Colorectal Cancer recently published recommendations for endoscopic removal of precancerous colorectal lesions.

According to lead author Tonya Kaltenbach, MD, of the University of California, San Francisco, and fellow panelists, the publication aims to improve complete resection rates, which can vary widely between endoscopists; almost one out of four lesions (22.7%) may be incompletely removed by some practitioners, leading to higher rates of colorectal cancer.

“[A]lthough the majority (50%) of postcolonoscopy colon cancers [are] likely due to missed lesions, close to one-fifth of incident cancers [are] related to incomplete resection,” the panelists wrote in Gastroenterology, referring to a pooled analysis of eight surveillance studies.

The panelists’ recommendations, which were based on both evidence and clinical experience, range from specific polyp removal techniques to guidance for institution-wide quality assurance of polypectomies. Each statement is described by both strength of recommendation and level of evidence, the latter of which was determined by Grading of Recommendations, Assessment, Development, and Evaluation Ratings of Evidence (GRADE) criteria. Recommendations were written by a panel of nine experts and approved by the governing boards of the three societies they represented – the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy. 

Central to the publication are recommended polypectomy techniques for specific types of lesions.

“Polypectomy techniques vary widely in clinical practice,” the panelists wrote. “They are often driven by physician preference based on how they were taught and on trial and error, due to the lack of standardized training and the paucity of published evidence. In the past decade, evidence has evolved on the superiority of specific methods.”

“Optimal techniques encompass effectiveness, safety, and efficiency,” they wrote. “Colorectal lesion characteristics, including location, size, morphology, and histology, influence the optimal removal method.”

For lesions up to 9 mm, the panelists recommended cold snare polypectomy “due to high complete resection rates and safety profile.” In contrast, they recommended against both cold and hot biopsy forceps, which have been associated with higher rates of incomplete resection. Furthermore, they cautioned that hot biopsy forceps may increase risks of complications and produce inadequate tissue samples for histopathology.

For nonpedunculated lesions between 10 and 19 mm, guidance is minimal. The panelists recommended cold or hot snare polypectomy, although this statement was conditional and based on low-quality evidence.

Recommendations were more extensive for large nonpedunculated lesions (at least 20 mm). For such lesions, the panelists strongly recommended endoscopic mucosal resection (EMR). They emphasized that large lesions should be removed in the fewest possible pieces by an appropriately experienced endoscopist during a single colonoscopy session. The panelists recommended the use of a viscous injection solution with a contrast agent and adjuvant thermal ablation of the post-EMR margin. They recommended against the use of tattoo as a submucosal injection solution, and ablation of residual lesion tissue that is endoscopically visible. Additional recommendations for large lesions, including prophylactic closure of resection defects and coagulation techniques, were based on low-quality evidence.

For pedunculated lesions greater than 10 mm, the panelists recommended hot snare polypectomy. For pedunculated lesions with a head greater than 20 mm or a stalk thickness greater than 5 mm, they recommended prophylactic mechanical ligation.

Beyond lesion assessment and removal, recommendations addressed lesion marking, equipment, surveillance, and quality of polypectomy.

Concerning quality, the panelists recommended that endoscopists participate in a quality assurance program that documents adverse events, and that institutions use standardized polypectomy competency assessments, such as Cold Snare Polypectomy Competency Assessment Tool and/or Direct Observation of Polypectomy Skills.

“Focused teaching is needed to ensure the optimal endoscopic management of colorectal lesions,” the panelists wrote. They went on to suggest that “development and implementation of polypectomy quality metrics may be necessary to optimize practice and outcomes.”

“For example, the type of resection method used for the colorectal lesion removal in the procedure report should be documented, and the inclusion of adequate resection technique as a quality indicator in colorectal cancer screening programs should be considered,” they wrote. “Adverse events, including bleeding, perforation, hospital admissions, and the number of benign colorectal lesions referred for surgical management, should be measured and reported. Finally, standards for pathology preparation and reporting of lesions suspicious for submucosal invasion should be in place to provide accurate staging and management.”

The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Kaltenbach T et al. Gastroenterology. 2020 Jan 18. doi: 10.1053/j.gastro.2019.12.018.

The U.S. Multi-Society Task Force (USMSTF) on Colorectal Cancer recently published recommendations for endoscopic removal of precancerous colorectal lesions.

According to lead author Tonya Kaltenbach, MD, of the University of California, San Francisco, and fellow panelists, the publication aims to improve complete resection rates, which can vary widely between endoscopists; almost one out of four lesions (22.7%) may be incompletely removed by some practitioners, leading to higher rates of colorectal cancer.

“[A]lthough the majority (50%) of postcolonoscopy colon cancers [are] likely due to missed lesions, close to one-fifth of incident cancers [are] related to incomplete resection,” the panelists wrote in Gastroenterology, referring to a pooled analysis of eight surveillance studies.

The panelists’ recommendations, which were based on both evidence and clinical experience, range from specific polyp removal techniques to guidance for institution-wide quality assurance of polypectomies. Each statement is described by both strength of recommendation and level of evidence, the latter of which was determined by Grading of Recommendations, Assessment, Development, and Evaluation Ratings of Evidence (GRADE) criteria. Recommendations were written by a panel of nine experts and approved by the governing boards of the three societies they represented – the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy. 

Central to the publication are recommended polypectomy techniques for specific types of lesions.

“Polypectomy techniques vary widely in clinical practice,” the panelists wrote. “They are often driven by physician preference based on how they were taught and on trial and error, due to the lack of standardized training and the paucity of published evidence. In the past decade, evidence has evolved on the superiority of specific methods.”

“Optimal techniques encompass effectiveness, safety, and efficiency,” they wrote. “Colorectal lesion characteristics, including location, size, morphology, and histology, influence the optimal removal method.”

For lesions up to 9 mm, the panelists recommended cold snare polypectomy “due to high complete resection rates and safety profile.” In contrast, they recommended against both cold and hot biopsy forceps, which have been associated with higher rates of incomplete resection. Furthermore, they cautioned that hot biopsy forceps may increase risks of complications and produce inadequate tissue samples for histopathology.

For nonpedunculated lesions between 10 and 19 mm, guidance is minimal. The panelists recommended cold or hot snare polypectomy, although this statement was conditional and based on low-quality evidence.

Recommendations were more extensive for large nonpedunculated lesions (at least 20 mm). For such lesions, the panelists strongly recommended endoscopic mucosal resection (EMR). They emphasized that large lesions should be removed in the fewest possible pieces by an appropriately experienced endoscopist during a single colonoscopy session. The panelists recommended the use of a viscous injection solution with a contrast agent and adjuvant thermal ablation of the post-EMR margin. They recommended against the use of tattoo as a submucosal injection solution, and ablation of residual lesion tissue that is endoscopically visible. Additional recommendations for large lesions, including prophylactic closure of resection defects and coagulation techniques, were based on low-quality evidence.

For pedunculated lesions greater than 10 mm, the panelists recommended hot snare polypectomy. For pedunculated lesions with a head greater than 20 mm or a stalk thickness greater than 5 mm, they recommended prophylactic mechanical ligation.

Beyond lesion assessment and removal, recommendations addressed lesion marking, equipment, surveillance, and quality of polypectomy.

Concerning quality, the panelists recommended that endoscopists participate in a quality assurance program that documents adverse events, and that institutions use standardized polypectomy competency assessments, such as Cold Snare Polypectomy Competency Assessment Tool and/or Direct Observation of Polypectomy Skills.

“Focused teaching is needed to ensure the optimal endoscopic management of colorectal lesions,” the panelists wrote. They went on to suggest that “development and implementation of polypectomy quality metrics may be necessary to optimize practice and outcomes.”

“For example, the type of resection method used for the colorectal lesion removal in the procedure report should be documented, and the inclusion of adequate resection technique as a quality indicator in colorectal cancer screening programs should be considered,” they wrote. “Adverse events, including bleeding, perforation, hospital admissions, and the number of benign colorectal lesions referred for surgical management, should be measured and reported. Finally, standards for pathology preparation and reporting of lesions suspicious for submucosal invasion should be in place to provide accurate staging and management.”

The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Kaltenbach T et al. Gastroenterology. 2020 Jan 18. doi: 10.1053/j.gastro.2019.12.018.

The U.S. Multi-Society Task Force (USMSTF) on Colorectal Cancer recently published recommendations for endoscopic removal of precancerous colorectal lesions.

According to lead author Tonya Kaltenbach, MD, of the University of California, San Francisco, and fellow panelists, the publication aims to improve complete resection rates, which can vary widely between endoscopists; almost one out of four lesions (22.7%) may be incompletely removed by some practitioners, leading to higher rates of colorectal cancer.

“[A]lthough the majority (50%) of postcolonoscopy colon cancers [are] likely due to missed lesions, close to one-fifth of incident cancers [are] related to incomplete resection,” the panelists wrote in Gastroenterology, referring to a pooled analysis of eight surveillance studies.

The panelists’ recommendations, which were based on both evidence and clinical experience, range from specific polyp removal techniques to guidance for institution-wide quality assurance of polypectomies. Each statement is described by both strength of recommendation and level of evidence, the latter of which was determined by Grading of Recommendations, Assessment, Development, and Evaluation Ratings of Evidence (GRADE) criteria. Recommendations were written by a panel of nine experts and approved by the governing boards of the three societies they represented – the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy. 

Central to the publication are recommended polypectomy techniques for specific types of lesions.

“Polypectomy techniques vary widely in clinical practice,” the panelists wrote. “They are often driven by physician preference based on how they were taught and on trial and error, due to the lack of standardized training and the paucity of published evidence. In the past decade, evidence has evolved on the superiority of specific methods.”

“Optimal techniques encompass effectiveness, safety, and efficiency,” they wrote. “Colorectal lesion characteristics, including location, size, morphology, and histology, influence the optimal removal method.”

For lesions up to 9 mm, the panelists recommended cold snare polypectomy “due to high complete resection rates and safety profile.” In contrast, they recommended against both cold and hot biopsy forceps, which have been associated with higher rates of incomplete resection. Furthermore, they cautioned that hot biopsy forceps may increase risks of complications and produce inadequate tissue samples for histopathology.

For nonpedunculated lesions between 10 and 19 mm, guidance is minimal. The panelists recommended cold or hot snare polypectomy, although this statement was conditional and based on low-quality evidence.

Recommendations were more extensive for large nonpedunculated lesions (at least 20 mm). For such lesions, the panelists strongly recommended endoscopic mucosal resection (EMR). They emphasized that large lesions should be removed in the fewest possible pieces by an appropriately experienced endoscopist during a single colonoscopy session. The panelists recommended the use of a viscous injection solution with a contrast agent and adjuvant thermal ablation of the post-EMR margin. They recommended against the use of tattoo as a submucosal injection solution, and ablation of residual lesion tissue that is endoscopically visible. Additional recommendations for large lesions, including prophylactic closure of resection defects and coagulation techniques, were based on low-quality evidence.

For pedunculated lesions greater than 10 mm, the panelists recommended hot snare polypectomy. For pedunculated lesions with a head greater than 20 mm or a stalk thickness greater than 5 mm, they recommended prophylactic mechanical ligation.

Beyond lesion assessment and removal, recommendations addressed lesion marking, equipment, surveillance, and quality of polypectomy.

Concerning quality, the panelists recommended that endoscopists participate in a quality assurance program that documents adverse events, and that institutions use standardized polypectomy competency assessments, such as Cold Snare Polypectomy Competency Assessment Tool and/or Direct Observation of Polypectomy Skills.

“Focused teaching is needed to ensure the optimal endoscopic management of colorectal lesions,” the panelists wrote. They went on to suggest that “development and implementation of polypectomy quality metrics may be necessary to optimize practice and outcomes.”

“For example, the type of resection method used for the colorectal lesion removal in the procedure report should be documented, and the inclusion of adequate resection technique as a quality indicator in colorectal cancer screening programs should be considered,” they wrote. “Adverse events, including bleeding, perforation, hospital admissions, and the number of benign colorectal lesions referred for surgical management, should be measured and reported. Finally, standards for pathology preparation and reporting of lesions suspicious for submucosal invasion should be in place to provide accurate staging and management.”

The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Kaltenbach T et al. Gastroenterology. 2020 Jan 18. doi: 10.1053/j.gastro.2019.12.018.

Women with breast cancer may be receiving treatments that are discordant with guideline recommendations for genetic subtypes of disease, based on a retrospective analysis of more than 20,000 patients.

Radiotherapy and chemotherapy practices were particularly out of alignment with guidelines, reported lead author Allison W. Kurian, MD, of Stanford (Calif.) University, and colleagues.

“Integrating genetic testing into breast cancer care has been complex and challenging,” the investigators wrote in JAMA Oncology. “There is wide variability in which clinicians order testing and disclose results, in the clinical significance of results, and in how clinicians interpret results to patients.”

According to the investigators, while germline testing is on the rise, little is known about how these test results are translating to clinical care.

To learn more, the investigators evaluated data from 20,568 women with stage 0-III breast cancer who entered the Surveillance, Epidemiology, and End Results registries of Georgia and California between 2014 and 2016.

Three treatment types were evaluated: surgery (bilateral vs. unilateral mastectomy), radiotherapy after lumpectomy, and chemotherapy. Treatment selection was compared with test results for breast cancer–associated genes, such as BRCA1/2, TP53, PTEN, and others. Associations were then compared with guideline recommendations.

Data analysis suggested that many clinicians were correctly using genetic test results to guide surgical decisions. For example, almost two-thirds (61.7%) of women with a BRCA mutation underwent bilateral mastectomy, compared with one-quarter (24.3%) who were BRCA negative (odds ratio, 5.52). For other pathogenic variants, the rate of bilateral mastectomy was still elevated, albeit to a lesser degree (OR, 2.41).

Generally, these practices align with recommendations, the investigators wrote, noting that research supports bilateral mastectomy with BRCA1/2, TP53, and PTEN variants, while data are lacking for other genetic subtypes.

Radiotherapy and chemotherapy practices were more discordant with guidelines. For example, women with a BRCA mutation were 78% less likely to receive radiotherapy after lumpectomy (OR, 0.22) and 76% more likely to receive chemotherapy for early-stage, hormone-positive disease (OR, 1.76). According to investigators, these findings suggest possible trends in undertreatment and overtreatment, respectively.

“We believe more research is needed to confirm our results and to evaluate long-term outcomes of pathogenic variant carriers to understand treatment decision making and consequences,” the investigators concluded.

The study was funded by the National Institutes of Health and the California Department of Public Health. The investigators reported relationships with Myriad Genetics, Genomic Health, Roche, and other companies.

SOURCE: Kurian AW et al. JAMA Oncol. 2020 Feb 6. doi: 10.1001/jamaoncol.2019.6400.

Women with breast cancer may be receiving treatments that are discordant with guideline recommendations for genetic subtypes of disease, based on a retrospective analysis of more than 20,000 patients.

Radiotherapy and chemotherapy practices were particularly out of alignment with guidelines, reported lead author Allison W. Kurian, MD, of Stanford (Calif.) University, and colleagues.

“Integrating genetic testing into breast cancer care has been complex and challenging,” the investigators wrote in JAMA Oncology. “There is wide variability in which clinicians order testing and disclose results, in the clinical significance of results, and in how clinicians interpret results to patients.”

According to the investigators, while germline testing is on the rise, little is known about how these test results are translating to clinical care.

To learn more, the investigators evaluated data from 20,568 women with stage 0-III breast cancer who entered the Surveillance, Epidemiology, and End Results registries of Georgia and California between 2014 and 2016.

Three treatment types were evaluated: surgery (bilateral vs. unilateral mastectomy), radiotherapy after lumpectomy, and chemotherapy. Treatment selection was compared with test results for breast cancer–associated genes, such as BRCA1/2, TP53, PTEN, and others. Associations were then compared with guideline recommendations.

Data analysis suggested that many clinicians were correctly using genetic test results to guide surgical decisions. For example, almost two-thirds (61.7%) of women with a BRCA mutation underwent bilateral mastectomy, compared with one-quarter (24.3%) who were BRCA negative (odds ratio, 5.52). For other pathogenic variants, the rate of bilateral mastectomy was still elevated, albeit to a lesser degree (OR, 2.41).

Generally, these practices align with recommendations, the investigators wrote, noting that research supports bilateral mastectomy with BRCA1/2, TP53, and PTEN variants, while data are lacking for other genetic subtypes.

Radiotherapy and chemotherapy practices were more discordant with guidelines. For example, women with a BRCA mutation were 78% less likely to receive radiotherapy after lumpectomy (OR, 0.22) and 76% more likely to receive chemotherapy for early-stage, hormone-positive disease (OR, 1.76). According to investigators, these findings suggest possible trends in undertreatment and overtreatment, respectively.

“We believe more research is needed to confirm our results and to evaluate long-term outcomes of pathogenic variant carriers to understand treatment decision making and consequences,” the investigators concluded.

The study was funded by the National Institutes of Health and the California Department of Public Health. The investigators reported relationships with Myriad Genetics, Genomic Health, Roche, and other companies.

SOURCE: Kurian AW et al. JAMA Oncol. 2020 Feb 6. doi: 10.1001/jamaoncol.2019.6400.

Women with breast cancer may be receiving treatments that are discordant with guideline recommendations for genetic subtypes of disease, based on a retrospective analysis of more than 20,000 patients.

Radiotherapy and chemotherapy practices were particularly out of alignment with guidelines, reported lead author Allison W. Kurian, MD, of Stanford (Calif.) University, and colleagues.

“Integrating genetic testing into breast cancer care has been complex and challenging,” the investigators wrote in JAMA Oncology. “There is wide variability in which clinicians order testing and disclose results, in the clinical significance of results, and in how clinicians interpret results to patients.”

According to the investigators, while germline testing is on the rise, little is known about how these test results are translating to clinical care.

To learn more, the investigators evaluated data from 20,568 women with stage 0-III breast cancer who entered the Surveillance, Epidemiology, and End Results registries of Georgia and California between 2014 and 2016.

Three treatment types were evaluated: surgery (bilateral vs. unilateral mastectomy), radiotherapy after lumpectomy, and chemotherapy. Treatment selection was compared with test results for breast cancer–associated genes, such as BRCA1/2, TP53, PTEN, and others. Associations were then compared with guideline recommendations.

Data analysis suggested that many clinicians were correctly using genetic test results to guide surgical decisions. For example, almost two-thirds (61.7%) of women with a BRCA mutation underwent bilateral mastectomy, compared with one-quarter (24.3%) who were BRCA negative (odds ratio, 5.52). For other pathogenic variants, the rate of bilateral mastectomy was still elevated, albeit to a lesser degree (OR, 2.41).

Generally, these practices align with recommendations, the investigators wrote, noting that research supports bilateral mastectomy with BRCA1/2, TP53, and PTEN variants, while data are lacking for other genetic subtypes.

Radiotherapy and chemotherapy practices were more discordant with guidelines. For example, women with a BRCA mutation were 78% less likely to receive radiotherapy after lumpectomy (OR, 0.22) and 76% more likely to receive chemotherapy for early-stage, hormone-positive disease (OR, 1.76). According to investigators, these findings suggest possible trends in undertreatment and overtreatment, respectively.

“We believe more research is needed to confirm our results and to evaluate long-term outcomes of pathogenic variant carriers to understand treatment decision making and consequences,” the investigators concluded.

The study was funded by the National Institutes of Health and the California Department of Public Health. The investigators reported relationships with Myriad Genetics, Genomic Health, Roche, and other companies.

SOURCE: Kurian AW et al. JAMA Oncol. 2020 Feb 6. doi: 10.1001/jamaoncol.2019.6400.

Apolipoprotein E epsilon 4 (APOE4) directly and independently exacerbates accumulation of alpha-synuclein in patients with Lewy body dementia, whereas APOE2 may have a protective effect, based on two recent studies involving mouse models and human patients.

These insights confirm the importance of APOE in synucleinopathies, and may lead to new treatments, according to Eliezer Masliah, MD, director of the division of neuroscience at the National Institute on Aging.

“These [studies] definitely implicate a role of APOE4,” Dr. Masliah said in an interview.

According to Dr. Masliah, previous studies linked the APOE4 genotype with cognitive decline in synucleinopathies, but underlying molecular mechanisms remained unknown.

“We [now] have more direct confirmation [based on] different experimental animal models,” Dr. Masliah said. “It also means that APOE4 could be a therapeutic target for dementia with Lewy bodies.”

The two studies were published simultaneously in Science Translational Medicine. The first study was conducted by Albert A. Davis, MD, PhD, of Washington University, St. Louis, and colleagues; the second was led by Na Zhao, MD, PhD, of the Mayo Clinic in Jacksonville, Fla.

“The studies are very synergistic, but used different techniques,” said Dr. Masliah, who was not involved in the studies.

Both studies involved mice that expressed a human variant of APOE: APOE2, APOE3, or APOE4. Three independent techniques were used to concurrently overexpress alpha-synuclein; Dr. Davis and colleagues used a transgenic approach, as well as striatal injection of alpha-synuclein preformed fibrils, whereas Dr. Zhao and colleagues turned to a viral vector. Regardless of technique, each APOE variant had a distinct impact on the level of alpha-synuclein accumulation.

“In a nutshell, [Dr. Davis and colleagues] found that those mice that have synuclein and APOE4 have a much more rapid progression of the disease,” Dr. Masliah said. “They become Parkinsonian much faster, but also, they become cognitively impaired much faster, and they have more synuclein in the brain. Remarkably, on the opposite side, those that were expressing APOE2, which we know is a protective allele, actually were far less impaired. So that’s really a remarkable finding.”

The study at the Mayo Clinic echoed these findings.

“Essentially, [Dr. Zhao and colleagues] had very similar results,” Dr. Masliah said. “[In mice expressing] APOE4, synuclein accumulation was worse and pathology was worse, and with APOE2, there was relative protection.”

Both studies found that the exacerbating effect of APOE4 translated to human patients.

Dr. Davis and colleagues evaluated data from 251 patients in the Parkinson’s Progression Markers Initiative. A multivariate model showed that patients with the APOE4 genotype had faster cognitive decline, an impact that was independent of other variables, including cerebrospinal fluid concentrations of amyloid beta and tau protein (P = .0119). This finding was further supported by additional analyses involving 177 patients with Parkinson’s disease from the Washington University Movement Disorders Center, and another 1,030 patients enrolled in the NeuroGenetics Research Consortium study.

Dr. Zhao and colleagues evaluated postmortem samples from patients with Lewy body dementia who had minimal amyloid pathology. Comparing 22 APOE4 carriers versus 22 age- and sex-matched noncarriers, they found that carriers had significantly greater accumulations of alpha-synuclein (P less than .05).

According to the investigators, these findings could have both prognostic and therapeutic implications.

“[I]t is intriguing to speculate whether APOE and other potential genetic risk or resilience genes could be useful as screening tools to stratify risk for individual patients,” Dr. Davis and colleagues wrote in their paper. They went on to suggest that APOE genotyping may one day be used to personalize treatments for patients with neurodegenerative disease.

According to Dr. Masliah, several treatment strategies are under investigation.

“There are some pharmaceutical companies and also some academic groups that have been developing antibodies against APOE4 for Alzheimer’s disease, but certainly that could also be used for dementia with Lewy bodies,” he said. “There are other ways. One could [be] to suppress the expression of APOE4 with antisense or other technologies.

“There is also a very innovative technology that has been developed by the group at the Gladstone Institutes in San Francisco, which is to switch APOE4 to APOE3.” This technique, Dr. Masliah explained, is accomplished by breaking a disulfide bond in APOE4, which opens the structure into an isoform that mimics APOE3. “They have developed small molecules that actually can break that bond and essentially chemically switch APOE4 to APOE3,” he said.

Although multiple techniques are feasible, Dr. Masliah stressed that these therapeutic efforts are still in their infancy.

“We need to better understand the mechanisms as to how APOE4 and alpha-synuclein interact,” he said. “I think we need a lot more work in this area.”

The Davis study was funded by the American Academy of Neurology/American Brain Foundation, the BrightFocus Foundation, the Mary E. Groff Charitable Trust, and others; the investigators reported additional relationships with Biogen, Alector, Parabon, and others. The Zhao study was funded by the National Institutes of Health and the Lewy Body Dementia Center Without Walls; the investigators reported no competing interests. Dr. Masliah reported no conflicts of interest.

SOURCES: Davis AA et al. Sci Transl Med. 2020 Feb 5. doi: 10.1126/scitranslmed.aay3069; Zhao N et al. Sci Transl Med. 2020 Feb 5. doi: 10.1126/scitranslmed.aay1809.

Apolipoprotein E epsilon 4 (APOE4) directly and independently exacerbates accumulation of alpha-synuclein in patients with Lewy body dementia, whereas APOE2 may have a protective effect, based on two recent studies involving mouse models and human patients.

These insights confirm the importance of APOE in synucleinopathies, and may lead to new treatments, according to Eliezer Masliah, MD, director of the division of neuroscience at the National Institute on Aging.

“These [studies] definitely implicate a role of APOE4,” Dr. Masliah said in an interview.

According to Dr. Masliah, previous studies linked the APOE4 genotype with cognitive decline in synucleinopathies, but underlying molecular mechanisms remained unknown.

“We [now] have more direct confirmation [based on] different experimental animal models,” Dr. Masliah said. “It also means that APOE4 could be a therapeutic target for dementia with Lewy bodies.”

The two studies were published simultaneously in Science Translational Medicine. The first study was conducted by Albert A. Davis, MD, PhD, of Washington University, St. Louis, and colleagues; the second was led by Na Zhao, MD, PhD, of the Mayo Clinic in Jacksonville, Fla.

“The studies are very synergistic, but used different techniques,” said Dr. Masliah, who was not involved in the studies.

Both studies involved mice that expressed a human variant of APOE: APOE2, APOE3, or APOE4. Three independent techniques were used to concurrently overexpress alpha-synuclein; Dr. Davis and colleagues used a transgenic approach, as well as striatal injection of alpha-synuclein preformed fibrils, whereas Dr. Zhao and colleagues turned to a viral vector. Regardless of technique, each APOE variant had a distinct impact on the level of alpha-synuclein accumulation.

“In a nutshell, [Dr. Davis and colleagues] found that those mice that have synuclein and APOE4 have a much more rapid progression of the disease,” Dr. Masliah said. “They become Parkinsonian much faster, but also, they become cognitively impaired much faster, and they have more synuclein in the brain. Remarkably, on the opposite side, those that were expressing APOE2, which we know is a protective allele, actually were far less impaired. So that’s really a remarkable finding.”

The study at the Mayo Clinic echoed these findings.

“Essentially, [Dr. Zhao and colleagues] had very similar results,” Dr. Masliah said. “[In mice expressing] APOE4, synuclein accumulation was worse and pathology was worse, and with APOE2, there was relative protection.”

Both studies found that the exacerbating effect of APOE4 translated to human patients.

Dr. Davis and colleagues evaluated data from 251 patients in the Parkinson’s Progression Markers Initiative. A multivariate model showed that patients with the APOE4 genotype had faster cognitive decline, an impact that was independent of other variables, including cerebrospinal fluid concentrations of amyloid beta and tau protein (P = .0119). This finding was further supported by additional analyses involving 177 patients with Parkinson’s disease from the Washington University Movement Disorders Center, and another 1,030 patients enrolled in the NeuroGenetics Research Consortium study.

Dr. Zhao and colleagues evaluated postmortem samples from patients with Lewy body dementia who had minimal amyloid pathology. Comparing 22 APOE4 carriers versus 22 age- and sex-matched noncarriers, they found that carriers had significantly greater accumulations of alpha-synuclein (P less than .05).

According to the investigators, these findings could have both prognostic and therapeutic implications.

“[I]t is intriguing to speculate whether APOE and other potential genetic risk or resilience genes could be useful as screening tools to stratify risk for individual patients,” Dr. Davis and colleagues wrote in their paper. They went on to suggest that APOE genotyping may one day be used to personalize treatments for patients with neurodegenerative disease.

According to Dr. Masliah, several treatment strategies are under investigation.

“There are some pharmaceutical companies and also some academic groups that have been developing antibodies against APOE4 for Alzheimer’s disease, but certainly that could also be used for dementia with Lewy bodies,” he said. “There are other ways. One could [be] to suppress the expression of APOE4 with antisense or other technologies.

“There is also a very innovative technology that has been developed by the group at the Gladstone Institutes in San Francisco, which is to switch APOE4 to APOE3.” This technique, Dr. Masliah explained, is accomplished by breaking a disulfide bond in APOE4, which opens the structure into an isoform that mimics APOE3. “They have developed small molecules that actually can break that bond and essentially chemically switch APOE4 to APOE3,” he said.

Although multiple techniques are feasible, Dr. Masliah stressed that these therapeutic efforts are still in their infancy.

“We need to better understand the mechanisms as to how APOE4 and alpha-synuclein interact,” he said. “I think we need a lot more work in this area.”

The Davis study was funded by the American Academy of Neurology/American Brain Foundation, the BrightFocus Foundation, the Mary E. Groff Charitable Trust, and others; the investigators reported additional relationships with Biogen, Alector, Parabon, and others. The Zhao study was funded by the National Institutes of Health and the Lewy Body Dementia Center Without Walls; the investigators reported no competing interests. Dr. Masliah reported no conflicts of interest.

SOURCES: Davis AA et al. Sci Transl Med. 2020 Feb 5. doi: 10.1126/scitranslmed.aay3069; Zhao N et al. Sci Transl Med. 2020 Feb 5. doi: 10.1126/scitranslmed.aay1809.

Apolipoprotein E epsilon 4 (APOE4) directly and independently exacerbates accumulation of alpha-synuclein in patients with Lewy body dementia, whereas APOE2 may have a protective effect, based on two recent studies involving mouse models and human patients.

These insights confirm the importance of APOE in synucleinopathies, and may lead to new treatments, according to Eliezer Masliah, MD, director of the division of neuroscience at the National Institute on Aging.

“These [studies] definitely implicate a role of APOE4,” Dr. Masliah said in an interview.

According to Dr. Masliah, previous studies linked the APOE4 genotype with cognitive decline in synucleinopathies, but underlying molecular mechanisms remained unknown.

“We [now] have more direct confirmation [based on] different experimental animal models,” Dr. Masliah said. “It also means that APOE4 could be a therapeutic target for dementia with Lewy bodies.”

The two studies were published simultaneously in Science Translational Medicine. The first study was conducted by Albert A. Davis, MD, PhD, of Washington University, St. Louis, and colleagues; the second was led by Na Zhao, MD, PhD, of the Mayo Clinic in Jacksonville, Fla.

“The studies are very synergistic, but used different techniques,” said Dr. Masliah, who was not involved in the studies.

Both studies involved mice that expressed a human variant of APOE: APOE2, APOE3, or APOE4. Three independent techniques were used to concurrently overexpress alpha-synuclein; Dr. Davis and colleagues used a transgenic approach, as well as striatal injection of alpha-synuclein preformed fibrils, whereas Dr. Zhao and colleagues turned to a viral vector. Regardless of technique, each APOE variant had a distinct impact on the level of alpha-synuclein accumulation.

“In a nutshell, [Dr. Davis and colleagues] found that those mice that have synuclein and APOE4 have a much more rapid progression of the disease,” Dr. Masliah said. “They become Parkinsonian much faster, but also, they become cognitively impaired much faster, and they have more synuclein in the brain. Remarkably, on the opposite side, those that were expressing APOE2, which we know is a protective allele, actually were far less impaired. So that’s really a remarkable finding.”

The study at the Mayo Clinic echoed these findings.

“Essentially, [Dr. Zhao and colleagues] had very similar results,” Dr. Masliah said. “[In mice expressing] APOE4, synuclein accumulation was worse and pathology was worse, and with APOE2, there was relative protection.”

Both studies found that the exacerbating effect of APOE4 translated to human patients.

Dr. Davis and colleagues evaluated data from 251 patients in the Parkinson’s Progression Markers Initiative. A multivariate model showed that patients with the APOE4 genotype had faster cognitive decline, an impact that was independent of other variables, including cerebrospinal fluid concentrations of amyloid beta and tau protein (P = .0119). This finding was further supported by additional analyses involving 177 patients with Parkinson’s disease from the Washington University Movement Disorders Center, and another 1,030 patients enrolled in the NeuroGenetics Research Consortium study.

Dr. Zhao and colleagues evaluated postmortem samples from patients with Lewy body dementia who had minimal amyloid pathology. Comparing 22 APOE4 carriers versus 22 age- and sex-matched noncarriers, they found that carriers had significantly greater accumulations of alpha-synuclein (P less than .05).

According to the investigators, these findings could have both prognostic and therapeutic implications.

“[I]t is intriguing to speculate whether APOE and other potential genetic risk or resilience genes could be useful as screening tools to stratify risk for individual patients,” Dr. Davis and colleagues wrote in their paper. They went on to suggest that APOE genotyping may one day be used to personalize treatments for patients with neurodegenerative disease.

According to Dr. Masliah, several treatment strategies are under investigation.

“There are some pharmaceutical companies and also some academic groups that have been developing antibodies against APOE4 for Alzheimer’s disease, but certainly that could also be used for dementia with Lewy bodies,” he said. “There are other ways. One could [be] to suppress the expression of APOE4 with antisense or other technologies.

“There is also a very innovative technology that has been developed by the group at the Gladstone Institutes in San Francisco, which is to switch APOE4 to APOE3.” This technique, Dr. Masliah explained, is accomplished by breaking a disulfide bond in APOE4, which opens the structure into an isoform that mimics APOE3. “They have developed small molecules that actually can break that bond and essentially chemically switch APOE4 to APOE3,” he said.

Although multiple techniques are feasible, Dr. Masliah stressed that these therapeutic efforts are still in their infancy.

“We need to better understand the mechanisms as to how APOE4 and alpha-synuclein interact,” he said. “I think we need a lot more work in this area.”

The Davis study was funded by the American Academy of Neurology/American Brain Foundation, the BrightFocus Foundation, the Mary E. Groff Charitable Trust, and others; the investigators reported additional relationships with Biogen, Alector, Parabon, and others. The Zhao study was funded by the National Institutes of Health and the Lewy Body Dementia Center Without Walls; the investigators reported no competing interests. Dr. Masliah reported no conflicts of interest.

SOURCES: Davis AA et al. Sci Transl Med. 2020 Feb 5. doi: 10.1126/scitranslmed.aay3069; Zhao N et al. Sci Transl Med. 2020 Feb 5. doi: 10.1126/scitranslmed.aay1809.

Sonographic flow-mediated dilation (FMD) of the brachial artery predicts renal dysfunction in patients with sickle cell disease (SCD), according to investigators.

Mohammed Haneefa Nizamudeen/Getty Images

This is the first study to show that FMD – a surrogate biomarker for endothelial dysfunction – inversely correlates with renal artery resistivity index (RARI) and serum cystatin C, reported lead author Oluwagbemiga Oluwole Ayoola, MBChB, of Obafemi Awolowo University in Ile-Ife, Nigeria, and colleagues.

“[B]rachial artery FMD is an essential test in the management of SCD patients for noninvasive assessment of the vascular endothelium,” the investigators wrote in Kidney360. They went on to suggest that FMD could be used to detect early renal impairment in sickle cell disease.

The study involved 44 patients with steady-state, homozygous SCD (HbSS) and 33 age- and sex-matched controls (HbAA). Eligibility criteria excluded individuals with risk factors for endothelial dysfunction, such as obesity, diabetes, and hypertension, as well as those with thalassemia carrier traits.

For each participant, various data were gathered, including demographic and clinical characteristics, serum assays, FMD measurement of the brachial artery, and RARI.

Results showed that patients with sickle cell disease had a significantly lower median FMD value than that of healthy controls (3.44 vs. 5.35; P = .043).

Among patients with SCD, FMD was negatively and independently correlated with RARI (r = -.307; P = .042) and serum cystatin C (r = -.372; P = .013), correlations that the investigators described as “modest.” FMD was not associated with any other biomarkers of SCD severity, such as homocysteine, fetal hemoglobin, or soluble platelet selectin.

Patients in the SCD cohort were further subdivided into two groups based on an FMD cut-off value of 5.35, which was the median measurement among healthy controls. This revealed that median cystatin C level was significantly higher in patients with an FMD value less than 5.35, compared with those who had an FMD value of 5.35 or more.

“[The study] findings suggest that SCD patients with impaired FMD are more likely to have impaired renal function,” the investigators wrote. The results support previous research, they added.

“Even though our findings show relationships rather than causation, we believe it is still a step forward in the ongoing quest to unravel the mysteries of this genetic disease,” they concluded. “Determining the exact age at which FMD impairment [begins] in children with sickle cell disease could be the subject of a future study.”

The study was funded by the Obafemi Awolowo University Teaching Hospital. The investigators reported no conflicts of interest.

SOURCE: Ayoola et al. Kidney360. 2020 Jan 30. doi: 10.34067/KID.0000142019.

Sonographic flow-mediated dilation (FMD) of the brachial artery predicts renal dysfunction in patients with sickle cell disease (SCD), according to investigators.

Mohammed Haneefa Nizamudeen/Getty Images

This is the first study to show that FMD – a surrogate biomarker for endothelial dysfunction – inversely correlates with renal artery resistivity index (RARI) and serum cystatin C, reported lead author Oluwagbemiga Oluwole Ayoola, MBChB, of Obafemi Awolowo University in Ile-Ife, Nigeria, and colleagues.

“[B]rachial artery FMD is an essential test in the management of SCD patients for noninvasive assessment of the vascular endothelium,” the investigators wrote in Kidney360. They went on to suggest that FMD could be used to detect early renal impairment in sickle cell disease.

The study involved 44 patients with steady-state, homozygous SCD (HbSS) and 33 age- and sex-matched controls (HbAA). Eligibility criteria excluded individuals with risk factors for endothelial dysfunction, such as obesity, diabetes, and hypertension, as well as those with thalassemia carrier traits.

For each participant, various data were gathered, including demographic and clinical characteristics, serum assays, FMD measurement of the brachial artery, and RARI.

Results showed that patients with sickle cell disease had a significantly lower median FMD value than that of healthy controls (3.44 vs. 5.35; P = .043).

Among patients with SCD, FMD was negatively and independently correlated with RARI (r = -.307; P = .042) and serum cystatin C (r = -.372; P = .013), correlations that the investigators described as “modest.” FMD was not associated with any other biomarkers of SCD severity, such as homocysteine, fetal hemoglobin, or soluble platelet selectin.

Patients in the SCD cohort were further subdivided into two groups based on an FMD cut-off value of 5.35, which was the median measurement among healthy controls. This revealed that median cystatin C level was significantly higher in patients with an FMD value less than 5.35, compared with those who had an FMD value of 5.35 or more.

“[The study] findings suggest that SCD patients with impaired FMD are more likely to have impaired renal function,” the investigators wrote. The results support previous research, they added.

“Even though our findings show relationships rather than causation, we believe it is still a step forward in the ongoing quest to unravel the mysteries of this genetic disease,” they concluded. “Determining the exact age at which FMD impairment [begins] in children with sickle cell disease could be the subject of a future study.”

The study was funded by the Obafemi Awolowo University Teaching Hospital. The investigators reported no conflicts of interest.

SOURCE: Ayoola et al. Kidney360. 2020 Jan 30. doi: 10.34067/KID.0000142019.

Sonographic flow-mediated dilation (FMD) of the brachial artery predicts renal dysfunction in patients with sickle cell disease (SCD), according to investigators.

Mohammed Haneefa Nizamudeen/Getty Images

This is the first study to show that FMD – a surrogate biomarker for endothelial dysfunction – inversely correlates with renal artery resistivity index (RARI) and serum cystatin C, reported lead author Oluwagbemiga Oluwole Ayoola, MBChB, of Obafemi Awolowo University in Ile-Ife, Nigeria, and colleagues.

“[B]rachial artery FMD is an essential test in the management of SCD patients for noninvasive assessment of the vascular endothelium,” the investigators wrote in Kidney360. They went on to suggest that FMD could be used to detect early renal impairment in sickle cell disease.

The study involved 44 patients with steady-state, homozygous SCD (HbSS) and 33 age- and sex-matched controls (HbAA). Eligibility criteria excluded individuals with risk factors for endothelial dysfunction, such as obesity, diabetes, and hypertension, as well as those with thalassemia carrier traits.

For each participant, various data were gathered, including demographic and clinical characteristics, serum assays, FMD measurement of the brachial artery, and RARI.

Results showed that patients with sickle cell disease had a significantly lower median FMD value than that of healthy controls (3.44 vs. 5.35; P = .043).

Among patients with SCD, FMD was negatively and independently correlated with RARI (r = -.307; P = .042) and serum cystatin C (r = -.372; P = .013), correlations that the investigators described as “modest.” FMD was not associated with any other biomarkers of SCD severity, such as homocysteine, fetal hemoglobin, or soluble platelet selectin.

Patients in the SCD cohort were further subdivided into two groups based on an FMD cut-off value of 5.35, which was the median measurement among healthy controls. This revealed that median cystatin C level was significantly higher in patients with an FMD value less than 5.35, compared with those who had an FMD value of 5.35 or more.

“[The study] findings suggest that SCD patients with impaired FMD are more likely to have impaired renal function,” the investigators wrote. The results support previous research, they added.

“Even though our findings show relationships rather than causation, we believe it is still a step forward in the ongoing quest to unravel the mysteries of this genetic disease,” they concluded. “Determining the exact age at which FMD impairment [begins] in children with sickle cell disease could be the subject of a future study.”

The study was funded by the Obafemi Awolowo University Teaching Hospital. The investigators reported no conflicts of interest.

SOURCE: Ayoola et al. Kidney360. 2020 Jan 30. doi: 10.34067/KID.0000142019.

Compared with patients who have normal baseline colonoscopy findings, those with low-risk adenomas may not have elevated risks of colorectal cancer (CRC) or CRC-related death, based on a retrospective analysis of more than 64,000 patients.

In contrast, patients with high-risk adenomas at baseline had significantly elevated rates of both CRC and CRC-related death, reported lead author Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco and colleagues.

With additional research, these findings may influence colonoscopy surveillance intervals, the investigators wrote in Gastroenterology.

“Current guidelines recommend that patients with a low-risk adenoma finding ... receive surveillance colonoscopy in 5-10 years, although in practice, clinicians often use even more frequent surveillance ... in this low-risk group,” they wrote. “The rationale for continued support of shorter-than-recommended surveillance intervals for patients with low-risk adenomas is unclear, but could stem from a lack of long-term population-based studies assessing colorectal cancer incidence and related deaths following low-risk adenoma removal or randomized trials evaluating optimal postpolypectomy surveillance intervals.”

To alleviate this knowledge gap, the investigators began by screening data from 186,046 patients who underwent baseline colonoscopy between 2004 and 2010 at 21 medical centers in California. Following exclusions based on family history, confounding gastrointestinal diseases, and incomplete data, 64,422 patients remained. Among these patients, the mean age was 61.6 years, with a slight female majority (54.3%). Almost three out of four patients (71.2%) had normal colonoscopy findings, followed by smaller proportions who were diagnosed with low-risk adenoma (17.0%) or high-risk adenoma (11.7%), based on United States Multi-Society Task Force guidelines.

After a median follow-up of 8.1 years, 117 patients who had normal colonoscopy findings developed CRC, 22 of whom died from the disease. In comparison, the low-risk adenoma group had 37 cases of CRC and 3 instances of CRC-related death, whereas the high-risk adenoma group had 60 cases of CRC and 13 instances of CRC-related death.

In the no-adenoma and low-risk groups, trends in age-adjusted CRC incidence rates were similar; in both cohorts, CRC incidence increased gradually over the decade following colonoscopy, with each group reaching approximately 50 cases per 100,000 person-years by year 10. In contrast, CRC incidence climbed rapidly in the high-risk adenoma group, ultimately peaking a decade later at almost 220 cases per 100,000 person-years. Average incidence rates per 100,000 person-years were similar among patients with no adenoma (31.1) and low-risk adenoma (38.8), but markedly higher among those with high-risk adenoma (90.8). At the end of the 14-year follow-up period, absolute risks of CRC among patients with no adenoma, low-risk adenoma, and high-risk adenoma were 0.51%, 0.57%, and 2.03%, respectively.

Based on covariate-adjusted Cox regression models, patients with low-risk adenoma did not have a significantly higher risk of CRC or CRC-related death than did patients with no adenoma. In contrast, patients with high-risk adenoma had significantly higher risks of CRC (hazard ratio, 2.61) and CRC-related death (HR, 3.94).

“These findings support guideline recommendations for intensive colonoscopy surveillance in [patients with high-risk adenomas at baseline],” the investigators wrote.

Considering similar risks between patients with low-risk adenomas and those with normal findings, the investigators suggested that longer surveillance intervals may be acceptable for both of these patient populations.

“Guidelines recommending comparable follow-up for low-risk adenomas and normal examinations, such as lengthening the surveillance interval to more than 5 years and possibly 10 years, may provide comparable cancer incidence and mortality benefits for these two groups,” they wrote.

Still, the investigators noted that study limitations – such as disparate rates of subsequent colonoscopy between groups – make it difficult to draw definitive, practice-changing conclusions.

“Additional studies, potentially including randomized trials, on the natural history of low-risk adenoma and normal findings without intervening surveillance exams before 10 years are needed to help guide future surveillance practices,” they concluded.

The study was supported by the National Cancer Institute and the American Gastroenterological Association. The investigators disclosed no conflicts of interest.

SOURCE: Lee JK et al. Gastroenterology. 2019 Oct 4. doi: 10.1053/j.gastro.2019.09.039.

Compared with patients who have normal baseline colonoscopy findings, those with low-risk adenomas may not have elevated risks of colorectal cancer (CRC) or CRC-related death, based on a retrospective analysis of more than 64,000 patients.

In contrast, patients with high-risk adenomas at baseline had significantly elevated rates of both CRC and CRC-related death, reported lead author Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco and colleagues.

With additional research, these findings may influence colonoscopy surveillance intervals, the investigators wrote in Gastroenterology.

“Current guidelines recommend that patients with a low-risk adenoma finding ... receive surveillance colonoscopy in 5-10 years, although in practice, clinicians often use even more frequent surveillance ... in this low-risk group,” they wrote. “The rationale for continued support of shorter-than-recommended surveillance intervals for patients with low-risk adenomas is unclear, but could stem from a lack of long-term population-based studies assessing colorectal cancer incidence and related deaths following low-risk adenoma removal or randomized trials evaluating optimal postpolypectomy surveillance intervals.”

To alleviate this knowledge gap, the investigators began by screening data from 186,046 patients who underwent baseline colonoscopy between 2004 and 2010 at 21 medical centers in California. Following exclusions based on family history, confounding gastrointestinal diseases, and incomplete data, 64,422 patients remained. Among these patients, the mean age was 61.6 years, with a slight female majority (54.3%). Almost three out of four patients (71.2%) had normal colonoscopy findings, followed by smaller proportions who were diagnosed with low-risk adenoma (17.0%) or high-risk adenoma (11.7%), based on United States Multi-Society Task Force guidelines.

After a median follow-up of 8.1 years, 117 patients who had normal colonoscopy findings developed CRC, 22 of whom died from the disease. In comparison, the low-risk adenoma group had 37 cases of CRC and 3 instances of CRC-related death, whereas the high-risk adenoma group had 60 cases of CRC and 13 instances of CRC-related death.

In the no-adenoma and low-risk groups, trends in age-adjusted CRC incidence rates were similar; in both cohorts, CRC incidence increased gradually over the decade following colonoscopy, with each group reaching approximately 50 cases per 100,000 person-years by year 10. In contrast, CRC incidence climbed rapidly in the high-risk adenoma group, ultimately peaking a decade later at almost 220 cases per 100,000 person-years. Average incidence rates per 100,000 person-years were similar among patients with no adenoma (31.1) and low-risk adenoma (38.8), but markedly higher among those with high-risk adenoma (90.8). At the end of the 14-year follow-up period, absolute risks of CRC among patients with no adenoma, low-risk adenoma, and high-risk adenoma were 0.51%, 0.57%, and 2.03%, respectively.

Based on covariate-adjusted Cox regression models, patients with low-risk adenoma did not have a significantly higher risk of CRC or CRC-related death than did patients with no adenoma. In contrast, patients with high-risk adenoma had significantly higher risks of CRC (hazard ratio, 2.61) and CRC-related death (HR, 3.94).

“These findings support guideline recommendations for intensive colonoscopy surveillance in [patients with high-risk adenomas at baseline],” the investigators wrote.

Considering similar risks between patients with low-risk adenomas and those with normal findings, the investigators suggested that longer surveillance intervals may be acceptable for both of these patient populations.

“Guidelines recommending comparable follow-up for low-risk adenomas and normal examinations, such as lengthening the surveillance interval to more than 5 years and possibly 10 years, may provide comparable cancer incidence and mortality benefits for these two groups,” they wrote.

Still, the investigators noted that study limitations – such as disparate rates of subsequent colonoscopy between groups – make it difficult to draw definitive, practice-changing conclusions.

“Additional studies, potentially including randomized trials, on the natural history of low-risk adenoma and normal findings without intervening surveillance exams before 10 years are needed to help guide future surveillance practices,” they concluded.

The study was supported by the National Cancer Institute and the American Gastroenterological Association. The investigators disclosed no conflicts of interest.

SOURCE: Lee JK et al. Gastroenterology. 2019 Oct 4. doi: 10.1053/j.gastro.2019.09.039.

Compared with patients who have normal baseline colonoscopy findings, those with low-risk adenomas may not have elevated risks of colorectal cancer (CRC) or CRC-related death, based on a retrospective analysis of more than 64,000 patients.

In contrast, patients with high-risk adenomas at baseline had significantly elevated rates of both CRC and CRC-related death, reported lead author Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco and colleagues.

With additional research, these findings may influence colonoscopy surveillance intervals, the investigators wrote in Gastroenterology.

“Current guidelines recommend that patients with a low-risk adenoma finding ... receive surveillance colonoscopy in 5-10 years, although in practice, clinicians often use even more frequent surveillance ... in this low-risk group,” they wrote. “The rationale for continued support of shorter-than-recommended surveillance intervals for patients with low-risk adenomas is unclear, but could stem from a lack of long-term population-based studies assessing colorectal cancer incidence and related deaths following low-risk adenoma removal or randomized trials evaluating optimal postpolypectomy surveillance intervals.”

To alleviate this knowledge gap, the investigators began by screening data from 186,046 patients who underwent baseline colonoscopy between 2004 and 2010 at 21 medical centers in California. Following exclusions based on family history, confounding gastrointestinal diseases, and incomplete data, 64,422 patients remained. Among these patients, the mean age was 61.6 years, with a slight female majority (54.3%). Almost three out of four patients (71.2%) had normal colonoscopy findings, followed by smaller proportions who were diagnosed with low-risk adenoma (17.0%) or high-risk adenoma (11.7%), based on United States Multi-Society Task Force guidelines.

After a median follow-up of 8.1 years, 117 patients who had normal colonoscopy findings developed CRC, 22 of whom died from the disease. In comparison, the low-risk adenoma group had 37 cases of CRC and 3 instances of CRC-related death, whereas the high-risk adenoma group had 60 cases of CRC and 13 instances of CRC-related death.

In the no-adenoma and low-risk groups, trends in age-adjusted CRC incidence rates were similar; in both cohorts, CRC incidence increased gradually over the decade following colonoscopy, with each group reaching approximately 50 cases per 100,000 person-years by year 10. In contrast, CRC incidence climbed rapidly in the high-risk adenoma group, ultimately peaking a decade later at almost 220 cases per 100,000 person-years. Average incidence rates per 100,000 person-years were similar among patients with no adenoma (31.1) and low-risk adenoma (38.8), but markedly higher among those with high-risk adenoma (90.8). At the end of the 14-year follow-up period, absolute risks of CRC among patients with no adenoma, low-risk adenoma, and high-risk adenoma were 0.51%, 0.57%, and 2.03%, respectively.

Based on covariate-adjusted Cox regression models, patients with low-risk adenoma did not have a significantly higher risk of CRC or CRC-related death than did patients with no adenoma. In contrast, patients with high-risk adenoma had significantly higher risks of CRC (hazard ratio, 2.61) and CRC-related death (HR, 3.94).

“These findings support guideline recommendations for intensive colonoscopy surveillance in [patients with high-risk adenomas at baseline],” the investigators wrote.

Considering similar risks between patients with low-risk adenomas and those with normal findings, the investigators suggested that longer surveillance intervals may be acceptable for both of these patient populations.

“Guidelines recommending comparable follow-up for low-risk adenomas and normal examinations, such as lengthening the surveillance interval to more than 5 years and possibly 10 years, may provide comparable cancer incidence and mortality benefits for these two groups,” they wrote.

Still, the investigators noted that study limitations – such as disparate rates of subsequent colonoscopy between groups – make it difficult to draw definitive, practice-changing conclusions.

“Additional studies, potentially including randomized trials, on the natural history of low-risk adenoma and normal findings without intervening surveillance exams before 10 years are needed to help guide future surveillance practices,” they concluded.

The study was supported by the National Cancer Institute and the American Gastroenterological Association. The investigators disclosed no conflicts of interest.

SOURCE: Lee JK et al. Gastroenterology. 2019 Oct 4. doi: 10.1053/j.gastro.2019.09.039.

On a population level, mailed fecal immunohistochemical tests (FITs) may catch more cases of advanced neoplasia than endoscopic methods, based on a Dutch screening study that invited more than 30,000 people to participate.

The relative success of mailed FIT screening was largely due a participation rate of 73%, compared with participation rates between 24% and 31% among those invited to undergo endoscopic screening, reported lead author Esmée J. Grobbee, MD, of Erasmus University Medical Centre in Rotterdam, the Netherlands, and colleagues.

In addition to high participation, previous research has shown that successful FIT screening depends upon continued adherence to the screening program, the investigators wrote in Clinical Gastroenterology and Hepatology. They noted that, in the present study, just two rounds of FIT were needed to outperform endoscopic methods, and that these comparative findings are a first for the field.

“No literature is available on the comparison between endoscopic screening strategies and multiple rounds of FIT screening,” the investigators wrote. “It is of key importance for policy makers to know the impact of different screening programs over multiple rounds with long-term follow-up.”

To this end, the investigators invited 30,052 screening-naive people in the Netherlands to participate in the present study. Each invitation was for one of three groups: once-only colonoscopy, once-only flexible sigmoidoscopy, or four rounds of FIT. All individuals received an advanced notification by mail followed 2 weeks later by a more substantial information kit (and first FIT test when applicable). If these steps received no response, a reminder was sent 6 weeks later.

Participants in the FIT group received one test every 2 years. Patients who had a positive FIT (hemoglobin concentration of at least 10 mcg Hb/g feces) were scheduled for a colonoscopy. Similarly, colonoscopies were performed in patients who had concerning findings on flexible sigmoidoscopy (e.g., sessile serrated adenoma. This sequential system reduced the relative number of colonoscopies in these two groups; colonoscopy rates in the FIT group and flexible sigmoidoscopy group were 13% and 3%, respectively, compared with the 24% participation rate in the colonoscopy group.

At a population level, FIT screening had the highest advanced neoplasia detection rate, at 4.5%, compared with 2.3% and 2.2% for screening by sigmoidoscopy and colonoscopy, respectively.

“In the intention-to-screen analysis, FIT already detected significantly more advanced neoplasia and colorectal cancer (CRC) after only 2 rounds of FIT, and this difference increased over rounds,” the investigators noted.

Again in the intention-to-screen population, mailed FIT detected three times as many cases of CRC than either of the other two groups (0.6% vs. 0.2% for both). In contrast, colonoscopy and sigmoidoscopy had higher detection rates for nonadvanced adenomas, at 5.6% and 3.7%, respectively, compared with 3.2% for FIT, although the investigators noted that nonadvanced adenomas are “of uncertain clinical importance.” Sessile adenoma detection rates were similar across all three groups.

The as-screened analysis revealed higher detection rates of advanced neoplasia for colonoscopy (9.1%), compared with sigmoidoscopy (7.4%) and FIT (6.1%). In the same analysis, detection rates of colorectal cancer (CRC) were comparable across all three groups.

According to the investigators, the CRC-related findings require careful interpretation.

“Comparing CRC detection rates of FIT and endoscopic screening is complex … because CRCs detected in FIT screening could in theory have been prevented in a once-only colonoscopy by the removal of adenomas,” they wrote.

Still, the key takeaway of the study – that FIT screening was the most effective strategy – may have practical implications on a global scale, according to the investigators.

“Because many countries are considering implementing screening programs, the findings of this study aid in deciding on choice of screening strategies worldwide, which is based on expected participation rates and available colonoscopy resources,” they wrote.

The study was funded by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

SOURCE: Grobbee EJ et al. Clin Gastro Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.015.

On a population level, mailed fecal immunohistochemical tests (FITs) may catch more cases of advanced neoplasia than endoscopic methods, based on a Dutch screening study that invited more than 30,000 people to participate.

The relative success of mailed FIT screening was largely due a participation rate of 73%, compared with participation rates between 24% and 31% among those invited to undergo endoscopic screening, reported lead author Esmée J. Grobbee, MD, of Erasmus University Medical Centre in Rotterdam, the Netherlands, and colleagues.

In addition to high participation, previous research has shown that successful FIT screening depends upon continued adherence to the screening program, the investigators wrote in Clinical Gastroenterology and Hepatology. They noted that, in the present study, just two rounds of FIT were needed to outperform endoscopic methods, and that these comparative findings are a first for the field.

“No literature is available on the comparison between endoscopic screening strategies and multiple rounds of FIT screening,” the investigators wrote. “It is of key importance for policy makers to know the impact of different screening programs over multiple rounds with long-term follow-up.”

To this end, the investigators invited 30,052 screening-naive people in the Netherlands to participate in the present study. Each invitation was for one of three groups: once-only colonoscopy, once-only flexible sigmoidoscopy, or four rounds of FIT. All individuals received an advanced notification by mail followed 2 weeks later by a more substantial information kit (and first FIT test when applicable). If these steps received no response, a reminder was sent 6 weeks later.

Participants in the FIT group received one test every 2 years. Patients who had a positive FIT (hemoglobin concentration of at least 10 mcg Hb/g feces) were scheduled for a colonoscopy. Similarly, colonoscopies were performed in patients who had concerning findings on flexible sigmoidoscopy (e.g., sessile serrated adenoma. This sequential system reduced the relative number of colonoscopies in these two groups; colonoscopy rates in the FIT group and flexible sigmoidoscopy group were 13% and 3%, respectively, compared with the 24% participation rate in the colonoscopy group.

At a population level, FIT screening had the highest advanced neoplasia detection rate, at 4.5%, compared with 2.3% and 2.2% for screening by sigmoidoscopy and colonoscopy, respectively.

“In the intention-to-screen analysis, FIT already detected significantly more advanced neoplasia and colorectal cancer (CRC) after only 2 rounds of FIT, and this difference increased over rounds,” the investigators noted.

Again in the intention-to-screen population, mailed FIT detected three times as many cases of CRC than either of the other two groups (0.6% vs. 0.2% for both). In contrast, colonoscopy and sigmoidoscopy had higher detection rates for nonadvanced adenomas, at 5.6% and 3.7%, respectively, compared with 3.2% for FIT, although the investigators noted that nonadvanced adenomas are “of uncertain clinical importance.” Sessile adenoma detection rates were similar across all three groups.

The as-screened analysis revealed higher detection rates of advanced neoplasia for colonoscopy (9.1%), compared with sigmoidoscopy (7.4%) and FIT (6.1%). In the same analysis, detection rates of colorectal cancer (CRC) were comparable across all three groups.

According to the investigators, the CRC-related findings require careful interpretation.

“Comparing CRC detection rates of FIT and endoscopic screening is complex … because CRCs detected in FIT screening could in theory have been prevented in a once-only colonoscopy by the removal of adenomas,” they wrote.

Still, the key takeaway of the study – that FIT screening was the most effective strategy – may have practical implications on a global scale, according to the investigators.

“Because many countries are considering implementing screening programs, the findings of this study aid in deciding on choice of screening strategies worldwide, which is based on expected participation rates and available colonoscopy resources,” they wrote.

The study was funded by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

SOURCE: Grobbee EJ et al. Clin Gastro Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.015.

On a population level, mailed fecal immunohistochemical tests (FITs) may catch more cases of advanced neoplasia than endoscopic methods, based on a Dutch screening study that invited more than 30,000 people to participate.

The relative success of mailed FIT screening was largely due a participation rate of 73%, compared with participation rates between 24% and 31% among those invited to undergo endoscopic screening, reported lead author Esmée J. Grobbee, MD, of Erasmus University Medical Centre in Rotterdam, the Netherlands, and colleagues.

In addition to high participation, previous research has shown that successful FIT screening depends upon continued adherence to the screening program, the investigators wrote in Clinical Gastroenterology and Hepatology. They noted that, in the present study, just two rounds of FIT were needed to outperform endoscopic methods, and that these comparative findings are a first for the field.

“No literature is available on the comparison between endoscopic screening strategies and multiple rounds of FIT screening,” the investigators wrote. “It is of key importance for policy makers to know the impact of different screening programs over multiple rounds with long-term follow-up.”

To this end, the investigators invited 30,052 screening-naive people in the Netherlands to participate in the present study. Each invitation was for one of three groups: once-only colonoscopy, once-only flexible sigmoidoscopy, or four rounds of FIT. All individuals received an advanced notification by mail followed 2 weeks later by a more substantial information kit (and first FIT test when applicable). If these steps received no response, a reminder was sent 6 weeks later.

Participants in the FIT group received one test every 2 years. Patients who had a positive FIT (hemoglobin concentration of at least 10 mcg Hb/g feces) were scheduled for a colonoscopy. Similarly, colonoscopies were performed in patients who had concerning findings on flexible sigmoidoscopy (e.g., sessile serrated adenoma. This sequential system reduced the relative number of colonoscopies in these two groups; colonoscopy rates in the FIT group and flexible sigmoidoscopy group were 13% and 3%, respectively, compared with the 24% participation rate in the colonoscopy group.

At a population level, FIT screening had the highest advanced neoplasia detection rate, at 4.5%, compared with 2.3% and 2.2% for screening by sigmoidoscopy and colonoscopy, respectively.

“In the intention-to-screen analysis, FIT already detected significantly more advanced neoplasia and colorectal cancer (CRC) after only 2 rounds of FIT, and this difference increased over rounds,” the investigators noted.

Again in the intention-to-screen population, mailed FIT detected three times as many cases of CRC than either of the other two groups (0.6% vs. 0.2% for both). In contrast, colonoscopy and sigmoidoscopy had higher detection rates for nonadvanced adenomas, at 5.6% and 3.7%, respectively, compared with 3.2% for FIT, although the investigators noted that nonadvanced adenomas are “of uncertain clinical importance.” Sessile adenoma detection rates were similar across all three groups.

The as-screened analysis revealed higher detection rates of advanced neoplasia for colonoscopy (9.1%), compared with sigmoidoscopy (7.4%) and FIT (6.1%). In the same analysis, detection rates of colorectal cancer (CRC) were comparable across all three groups.

According to the investigators, the CRC-related findings require careful interpretation.

“Comparing CRC detection rates of FIT and endoscopic screening is complex … because CRCs detected in FIT screening could in theory have been prevented in a once-only colonoscopy by the removal of adenomas,” they wrote.

Still, the key takeaway of the study – that FIT screening was the most effective strategy – may have practical implications on a global scale, according to the investigators.

“Because many countries are considering implementing screening programs, the findings of this study aid in deciding on choice of screening strategies worldwide, which is based on expected participation rates and available colonoscopy resources,” they wrote.

The study was funded by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

SOURCE: Grobbee EJ et al. Clin Gastro Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.015.